- Email: [email protected]
Effects of Monensin on the Metabolism of Periparturient Dairy Cows
Effects of Monensin on the Metabolism of Periparturient Dairy Cows K. A. STEPHENSON,* I. J. LEAN,* M. L. HYDE,* M. A. CURTIS,* J. K. GARVIN,* and L. B. LOWE† *Department of Animal Science, University of Sydney, Camden, New South Wales, Australia 2570 †Elanco Animal Health, Wharf Road, West Ryde, New South Wales, Australia 2114
ABSTRACT The effects of monensin on plasma concentrations and changes in plasma concentrations of energy metabolites and minerals over time were investigated using 24 multiparous Holstein cows. Cows were paired according to farm, predicted date of calving, and body condition score and were randomly allocated to two groups. Treated cows were given a ruminal bolus containing 32 g of monensin at 50 ± 7 d before predicted calving. Treated cows had lower plasma concentrations of glucose, free fatty acid (FFA), and b-hydroxybutyrate (BHBA) than did control cows before calving, indicating that monensin influenced energy metabolism. However, no significant differences in plasma concentrations of glucose, FFA, and BHBA were found between groups after calving. Plasma BHBA concentrations increased more before calving in control cows, and plasma FFA and urea concentrations increased significantly before calving in all cows. No significant differences in body weight, plasma concentrations of urea, or whole blood concentrations of glutathione peroxidase were detected between groups before or after calving. Plasma ceruloplasmin activity did not differ between groups before calving, but was significantly higher in treated cows after calving. Plasma concentrations of Ca did not significantly differ between groups before or after calving. Monensin altered both energy and mineral metabolism and has the potential to improve the health and production of dairy cows. ( Key words: monensin, metabolism, periparturient cows) Abbreviation key: Cp = ceruloplasmin, GSHPx = glutathione peroxidase. INTRODUCTION During early lactation, the mammary gland of dairy cows has a requirement for nutrients that is
Received September 29, 1995. Accepted September 13, 1996. 1997 J Dairy Sci 80:830–837
usually greater than that provided by feed intake. The consequent nutrient deficiency is met by partitioning nutrients from tissue stores and by mobilizing labile tissue reserves of lipid, protein, glycogen, and minerals. Uptake of glucose by the mammary gland during early lactation results in decreased plasma concentrations of glucose, which are strongly correlated with increased plasma concentrations of FFA and BHBA (18). Excessive mobilization of body tissue is associated with metabolic disorders such as ketonemia and fatty liver ( 6 ) . Administration of monensin may increase plasma concentrations of glucose (1, 10) by increasing ruminal propionate production ( 2 1 ) and possibly by mechanisms that are independent of ruminal function ( 2 ) . Increased glucose flux should decrease tissue mobilization and have beneficial impacts on the health and reproductive performance of cows. The requirement of mammary gland for minerals increases with the onset of lactation, and the sudden increase in demand for Ca is reflected in a marked decrease in plasma concentrations of Ca ( 1 4 ) and, in some cases, clinical hypocalcemia. Increased Ca demand is met by increased Ca absorption from the rumen and intestines and increased resorption from Ca stores in bone. Unfortunately, increased Ca flux from these sources is not evident until 24 to 48 h after calving (8, 9). Monensin increases the uptake of Ca from the intestines (26), influences the absorption of bivalent cations, and, therefore, may modify the risk or severity of parturient paresis. Similarly, absorption of Se ( 5 ) and Cu ( 3 4 ) is increased by monensin treatment. Deficiencies in Se have been associated with increased incidence of retained placenta ( 3 2 ) and uterine infection (12), and Se and Cu have important roles in antioxidant defense mechanisms. Increased availability of these minerals might modify the periparturient risk of disease for herds that are deficient in Se and Cu. Abe et al. ( 1 ) commenced monensin treatment of lactating cows in the period immediately after calving ( 1 ) , and Sauer et al. ( 2 2 ) commenced monensin treatment before calving. Those studies (1, 22) found
830
831
MONENSIN AND PERIPARTURIENT METABOLISM
All cows were fed on pasture. For nonlactating cows, the pasture consisted primarily of couch ( Cynodon dactylon) and kikuyu ( Pennisetum clandestinum) . After calving, all cows were fed pasture containing primarily kikuyu and ryegrass ( Lolium spp.). In addition, cows from one farm were fed pelleted concentrate at approximately 4 kg/d, and cows from the second farm were fed pellets at approximately 10 kg/d and 1 kg of hay beginning 2 wk before calving and when milking. The pelleted concentrates used on both farms were identical in formulation and included approximately 30% sorghum, 50% wheat bran and pollard, 8% meat meal, 8% cottonseed meal, 1% tallow, and 1% sodium bicarbonate to provide 18% CP. Feed samples were collected every 14 d and analyzed by near infrared reflectance spectroscopy using equations developed for local pastures and concentrates (28). Analyses of pasture and pellets are presented in Figures 1 and 2 and Table 1, respectively. All cows were weighed and scored for body condition every 14 d. The accuracy of the scales was verified by placing a known weight on the scales before and after weighing. The standard error was < ±5 kg. Body condition was scored using 0.25 increments ( 1 = thin to 5 = obese) ( 7 ) . Blood (25 ml) was taken weekly from the coccygeal vessels using vacutainers (Becton-Dickinson Vacutainer Systems, Rutherford, NJ). The last blood samples were taken 3 wk after calving. The blood was transported on ice before centrifugation, decanting, and storage at –20°C for later analyses. Enzymatic colorimetric methods were used to determine glucose (24), BHBA (36), FFA (NEFA-C; Wako Pure Chemicals Industries, Ltd., Osaka, Japan), plasma urea (11), GSHPx (32), and Cp activities (13). Plasma Ca was determined by atomic absorption spectroscopy (Varian Spectra AA-20; Varian Techtron, Pty. Ltd., Melbourne, Victoria, Australia).
higher plasma concentrations of glucose and lower plasma concentrations of ketones and FFA after calving. The goal of this study was to evaluate the effects of monensin administered in a controlled-release capsule on metabolic and mineral responses of cows during the periparturient period. Because feed intake can be depressed shortly after monensin treatment (23), we administered the capsules early in the dry period when nutritional requirements are lower. Our hypothesis was that monensin administration would increase plasma concentrations of glucose, ceruloplasmin ( Cp) , glutathione peroxidase ( GSHPx) , and Ca and decrease plasma concentrations of FFA, urea, and BHBA. This study examined the impact of monensin capsules that were administered during the dry period at 50 d before expected calving on metabolism of dairy cows and evaluated the periods when treatment effects of monensin were likely to be the greatest. MATERIALS AND METHODS Twenty-four multiparous Holstein-Friesian cows from two farms were used in the study, which was conducted over a 12-wk period during autumn in New South Wales, Australia. Cows entered the trial at 50 ± 7 d before predicted calving. Upon entering the trial, cows were paired according to body condition score, calving date, and farm before being allocated randomly into treatment groups. The operators handling the cows were unaware of treatment allocation. The control group was given a sham treatment (the gun used for capsule administration was placed in the mouth of the cow and was discharged), and the treatment group was given one capsule of controlledrelease monensin (Rumensin Antibloat Capsule; Elanco Animal Health, West Ryde, New South Wales, Australia) orally. The capsules contained 32 g of monensin, which was released at 300 mg/d over approximately 100 d.
TABLE 1. Analysis of concentrate hay and pellets.1 Energy
CP
ME2
Hay Pellets
(MJ of X 7.64 12.254
of DM/kg) SD 0.31
X 10.53 19.02
SD 4.74 0.51
Crude fiber ( % of DM) X SD NA3 9.85 1.37
Fat X NA 6.67
SD 0.33
1Means
for seven pellet and two hay analyses. energy. 3Not available. 4Estimated from crude fiber, CP, and fat. 2Metabolizable
Journal of Dairy Science Vol. 80, No. 5, 1997
832
STEPHENSON ET AL.
Figure 1. Metabolizable energy ( M E ) content of pastures during the trial. Legend: ⁄ = pasture fed to dry cows on farm 1, ÿ = pasture fed to dry cows on farm 2, ♦ = pasture fed to lactating cows on farm 1, and … = pasture fed to lactating cows on farm 2.
outcome variables did not differ over time, and that the pattern of change in variables between treatment groups over time was not different. The effects of farm, interval from treatment to calving, and pretreatment differences between group values were adjusted for using covariables. Power calculations on the results analyzed by repeated measures were made using SOLO Statistical System Power Analysis (BMDP Statistical Software Inc.). Significance was tested at P ≤ 0.1 because of the relatively small number of cows used in the study. Thus, the statistical power in this study was relatively low. Plasma BHBA had the largest difference between means, and the coefficient of variation was low; the power to evaluate the difference in means was greatest for this variable. The power to evaluate the difference of 24% in means for plasma BHBA differences between treatments, treatment by time effects (differences between groups in the pattern of change in BHBA over time), and change in BHBA over time was 0.30, 0.59, and 0.85, respectively. RESULTS AND DISCUSSION
Body weight and plasma concentrations of glucose, FFA, BHBA, plasma urea, Cp, GSHPx, and Ca were assessed by repeated measures of variance with covariables (BMDP 2V; BMDP Statistical Software Inc., Los Angeles, CA). The covariables were farm, interval from treatment to calving, and pretreatment values of the variables. Because the direction of some responses varied before and after calving and because 1 cow died of milk fever at calving, data before and after calving were analyzed separately, except for BW data. Because of the variation in time to calving, some values between 50 and 35 d before calving were missed; consequently, only data collected from blood analysis between 35 d before calving and 14 d after calving were analyzed. Plasma Ca determinations were made on samples collected before treatment and between 14 d before and 14 d after calving. Body weight data were collected every 14 d and were evaluated for the period between 28 d before and 14 d after calving. Missing values were extrapolated or interpolated to allow analysis, and one extrapolated value each was needed for data for the FFA, BHBA, Cp, and GSHPx. Plasma urea and glucose required one extrapolated and one interpolated value, and BW required one extrapolated and four interpolated values. The effects of treatment, time, and treatment by time effects (differences between treatment groups in change of variables over time) were tested. The null hypotheses examined were that the effect of treatment on outcome variables was not significant, that Journal of Dairy Science Vol. 80, No. 5, 1997
Although Sauer et al. ( 2 2 ) commenced monensin treatment before calving, we could find no previously published data on the effects of monensin in dry cows. The mean interval from treatment to calving was 50.3 ± 6.9 d. For all cows, plasma concentrations of glucose (Figure 3 ) remained stable ( P = 0.73), and plasma concentrations of FFA (Figure 4 ) increased ( P =
Figure 2. Crude protein content of pastures during the trial. Legend: ⁄ = pasture fed to dry cows on farm 1, ÿ = pasture fed to dry cows on farm 2, ♦ = pasture fed to lactating cows on farm 1, and … = pasture fed to lactating cows on farm 2.
MONENSIN AND PERIPARTURIENT METABOLISM
833
Figure 3. Mean plasma glucose concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
Figure 5. Mean plasma BHBA concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
0.001), as calving approached. Plasma concentrations of BHBA (Figure 5 ) tended to increase ( P = 0.11) for both groups, but concentrations increased more ( P = 0.05) for control cows as calving approached. These findings of increased plasma concentrations of FFA and BHBA and relatively stable glucose concentrations immediately prior to calving for cows fed diets based on pasture were very similar to those results found by Vazquez-Anon et al. ( 3 5 ) for cows that were
fed rations based on hay and silage in herds under housed conditions. In our study, plasma glucose concentrations were lower ( P = 0.10) in treated cows than in control cows before calving. Previous studies (1, 10), however, have identified significant increases in blood concentrations of glucose in cows treated with monensin after calving (1, 10), which initially appear to be inconsistent with the glucogenic action of monensin. However, increased glucogenic flux might have stimulated the release of insulin and resulted in lower plasma concentrations of glucose in treated cows, perhaps from an increased partitioning of glucose to the rapidly growing fetus ( 4 ) . Increased birth weight of calves born to cows treated with monensin before calving has been reported (N. B. Williamson, 1996, unpublished data). A decrease in glucose concentrations is also consistent with reduced rates of lipogenesis for bovine adipocytes harvested after calving compared with those harvested before calving ( 1 9 ) and with the lower sensitivity of adipocytes harvested after calving to insulin ( 3 ) . However, partitioning of glucose to adipose tissue would be a minor effect of the limited role of glucose in ruminant adipose synthesis. Treated cows had lower plasma concentrations of FFA ( P = 0.06) and BHBA ( P = 0.08) before calving, a result that is consistent with changes in those metabolites after calving that have been reported in other studies (1, 22, 30). The lower concentrations of plasma BHBA and FFA might have resulted from several actions of monensin, including a decrease in the ruminal acetate to propionate ratio (21), which
Figure 4. Mean plasma FFA concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
Journal of Dairy Science Vol. 80, No. 5, 1997
834
STEPHENSON ET AL.
Figure 6. Mean plasma urea concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
subsequently increased hepatic oxidation of glucose in the TCA cycle; a decrease in ruminal production of butyrate (25), which reduced dietary entry of BHBA precursors; a glucogenic effect that was independent of ruminal function modification ( 2 ) ; reduced demand for FFA mobilization as a result of increased glucose availability; or decreased ruminal degradation of dietary protein (20), which increased amino acid availability for gluconeogenesis. However, no differences in plasma urea concentrations (Figure 6 ) were detected between treatment groups before ( P = 0.85) or after ( P = 0.18) calving, possibly indicating that any increase in the available protein was negligible or that the measurement of plasma concentrations of urea was not sufficiently sensitive to detect differences in protein metabolism between the groups. Plasma concentrations of urea ( P = 0.001), increased before calving in association with greater protein availability in rations and body tissue mobilization in a manner similar to the increase in FFA concentrations. Body weights decreased over time ( P = 0.001) for all cows (Figure 7), but no differences in BW were found between treatment groups ( P = 0.47). After calving, glucose concentrations did not differ between treatment groups ( P = 0.73), a finding that was consistent with the results of Sauer et al. ( 2 2 ) but not with those of Abe et al. ( 1 ) , who found higher glucose concentrations in cows treated with monensin. Sauer et al. (22), however, noted that plasma concentrations of glucose were higher in cows treated with monensin, and the power to determine differJournal of Dairy Science Vol. 80, No. 5, 1997
ences between groups in that study was low. Monensin might have increased glucose availability, but high demands for glucose by the mammary gland of the lactating cow kept plasma concentrations relatively constant. Most studies investigating changes in energy metabolites in the periparturient period have evaluated plasma concentrations of metabolites after calving. In the present study, the pattern of change in plasma concentrations of glucose, FFA, and BHBA after calving was typical of that previously found in studies by Abe et al. ( 1 ) and Lean et al. ( 1 8 ) in which plasma concentrations of glucose declined and plasma concentrations of BHBA and FFA increased. No differences were detected in mean plasma concentrations of FFA ( P = 0.45) and BHBA ( P = 0.32) or changes in plasma concentrations of FFA ( P = 0.74) and BHBA ( P = 0.65) between groups after calving, although plasma concentrations of FFA and BHBA were lower in the treated cows. Other studies (1, 22) have reported decreased plasma concentrations of FFA and BHBA in cows treated with monensin. In this study, plasma concentrations of FFA and BHBA before and after calving suggest that FFA mobilization and BHBA production were reduced, but the statistical power of the study was insufficient to detect changes in the concentrations of these metabolites after calving. The GSHPx activity (Figure 8 ) tended to increase ( P = 0.11) prior to calving. Whole blood concentra-
Figure 7. Mean BW of treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
MONENSIN AND PERIPARTURIENT METABOLISM
Figure 8. Mean blood glutathione peroxidase concentrations [in hemoglobin (Hb)] in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
tions of GSHPx did not differ between treatment groups before ( P = 0.98) or after ( P = 0.98) calving, nor did the pattern of change differ before or after calving ( P = 0.83 and P = 0.13, respectively). On both farms used in the study, GSHPx activity was low (29), which indicated Se deficiency (33), despite considerable interlaboratory variation in GSHPx assay methods (17). The GSHPx present in blood is predominantly present in erythrocytes, which remain in circulation for approximately 100 d. Whole blood concentrations of GSHPx, therefore, reflect Se intake over the previous 100 d and may not reflect immediate changes in the availability of Se. Although Costa et al. ( 5 ) found that Se uptake was increased by monensin administration in steers, Vay Ryssen ( 3 4 ) found no significant difference in blood concentrations of GSHPx between cows treated with monensin and control cows. Horvath et al. (15), however, found significant increased in blood concentrations of GSHPx in pigs within 28 d of the commencement of monensin administration, indicating the potential for monensin supplementation to modify Se metabolism and GSHPx activity over a relatively short period. Plasma Cp activity (Figure 9 ) did not differ between treatment groups before calving ( P = 0.87) but was higher in treated cows after calving ( P = 0.04). Changes over time in plasma Cp activity were not different between groups before ( P = 0.85) or after ( P = 0.34) calving. The increase in Cp that occurred in treated cows after calving might reflect an improved capacity of treated cows to mobilize Cp, an acute
835
Figure 9. Mean ceruloplasmin concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
phase protein that is important in controlling oxidative challenge from free radicals. Ceruloplasmin is an accurate measure of Cu status when Cu supply is deficient because Cp-binding sites are unsaturated at a low Cu intake. Cows in this trial might have been deficient in Cu because soils in the area are deficient in Cu ( 1 6 ) and the farms did not provide supplemental Cu. Van Ryssen ( 3 4 ) demonstrated that monensin increased Cu activity in the liver of sheep by using
Figure 10. Mean plasma Ca concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements. Journal of Dairy Science Vol. 80, No. 5, 1997
836
STEPHENSON ET AL.
liver biopsies, a more sensitive measure of Cu status than Cp. Our results support the findings of Van Ryssen (34), indicating a potential for monensin to improve Cu absorption. Mean plasma concentrations of Ca (Figure 10) did not differ between treatment groups before ( P = 0.99) or after ( P = 0.62) calving. Plasma Ca decreased ( P = 0.001) as cows neared parturition, which was consistent with results of other studies (14), and there was a difference ( P < 0.001) between groups in the pattern of change in plasma concentrations of Ca; control cows maintained more constant concentrations of Ca in plasma. Previous work with steers (26, 27) has found that Ca absorption increased after monensin treatment. Because 1 treated cow died of milk fever, the effect of monensin treatment on the risk of hypocalcemia and related disorders should be examined in large randomized clinical trials. Our study found differences between treated cows and control cows in concentrations of glucose, BHBA, and FFA and in Cp and Ca metabolism during the period of adaptation to lactation. The study also identified times when plasma metabolites were likely to differ between treatment groups. The decreased plasma concentrations of glucose prior to calving in treated cows probably reflect greater glucose availability and loss to the fetus. The reduction in plasma concentrations of FFA and BHBA should act to reduce the risk of metabolic disorders related to lipid mobilization after calving. Increased Cp activity indicated enhanced Cu absorption and a greater potential for control of oxidative challenge. Further studies should be conducted to explore the potential for monensin to modify both the metabolic adaptive responses of dairy cows to lactation and to examine the effects of monensin on health, reproduction, and production on a population basis. ACKNOWLEDGMENTS The authors thank John McClure, the late Christine Gerard, Diane Ryan, and Nancy Kelly for technical assistance and Elanco Animal Health, West Ryde, New South Wales, Australia, for financial support. REFERENCES 1 Abe, N., I. J. Lean, A. Rabiee, J. Porter, and C. Graham. 1994. Effects of sodium monensin on reproductive performance of dairy cattle. II. Effects on metabolites in plasma, resumption of ovarian cyclicity and oestrus in lactating cows. Aust. Vet. J. 71: 277. 2 Armstrong, J. D., and J. W. Spears. 1988. Intravenous administration of ionophores in ruminants: effects on metabolism independent of the rumen. J. Anim. Sci. 66:1807. Journal of Dairy Science Vol. 80, No. 5, 1997
3 Baldwin, R. L., and N. E. Smith. 1971. Intermediary aspects and tissue interactions of ruminant fat metabolism. J. Dairy Sci. 54:583. 4 Bell, A. W. 1995. Regulation of organic nutrient metabolism during transition from late pregnancy to early lactation. J. Anim. Sci. 73:2804. 5 Costa, N. D., P. T. Gleed, B. F. Sanson, H. W. Symonds, and W. M. Allen. 1985. Monensin and narasin increase selenium and zinc absorption in steers. Page 472 in Trace Element Metabolism in Man and Animals. C. F. Mills, I. Bremner, and J. K. Chesters, ed. Commonw. Agric. Bur., Slough, England. 6 Dohoo, I. R., and S. W. Martin. 1984. Subclinical ketosis: prevalence and associations with production and disease. Can. J. Comp. Med. 48:1. 7 Edmondson, A. J., I. J. Lean, L. D. Weaver, T. Farver, and G. Webster. 1989. A body condition scoring chart for Holstein dairy cattle. J. Dairy Sci. 72:68. 8 Goff, J. P., R. L. Horst, E. T. Littledike, A. Boris, and M. R. Uskokovic. 1986. Bone resorption, renal function and mineral status in cows treated with 1,25-dihydroxy-cholecalciferol and its 24-fluro analogues. J. Nutr. 116:150. 9 Goff, J. P., E. T. Littledike, and R. L. Horst. 1986. Effect of synthetic bovine parathyroid hormone in dairy cows: prevention of hypocalcemic parturient paresis. J. Dairy Sci. 69:2278. 10 Grings, E. E., and J. R. Males. 1987. Performance, blood and ruminal characteristics of cows receiving monensin and a magnesium supplement. J. Anim. Sci. 66:566. 11 Gutman, N. I., and H. U. Bergmeyer. 1974. Urea. Page 1791 in Methods of Enzymatic Analysis. 2nd ed. Vol. 4. Acad. Press, New York, NY. 12 Harrison, J. H., D. D. Hancock, N. St. Pierre, H. R. Conrad, and W. R. Harvey. 1986. Effect of selenium treatment on uterine involution in the dairy cow. J. Dairy Sci. 69:1421. 13 Henry, R. J., N. Chiamori, S. L. Jacobs, and M. Segalove. 1960. Determination of ceruloplasmin oxidase in serum. Proc. Soc. Exp. Biol. Med. 104:620. 14 Horst, R. L. 1986. Regulation of calcium and phosphorus homeostasis in the dairy cows. J. Dairy Sci. 69:604. 15 Horvath, C. J., H. D. Stowe, and E. R. Miller. 1992. Effects of monensin on selenium status and related factors in genetically hypo- and hyperselenemic growing swine. Am. J. Vet. Res. 53: 2109. 16 Kellaway, R. C., R. J. Tassell, E. Havilah, N. Sriskandarajah, and A. Andrews. 1993. Nutrient balance in the diet of grazing dairy cows. Aust. J. Agric. Res. 44:423. 17 Langlands, J. P., J. F. Wilkins, J. E. Bowles, A. J. Smith, and R. F. Webb. 1981. Selenium concentration in the blood of ruminants grazing in northern NSW. I. Analysis of samples collected in the national brucellosis eradication scheme. Aust. J. Agric. Res. 32:511. 18 Lean, I. J., T. B. Farver, H. F. Troutt, M. L. Bruss, J. C. Galland, R. L. Baldwin, C. A. Holmberg, and L. D. Weaver. 1992. Time series cross-correlation analysis of postparturient relationships among serum metabolites and yield variables in Holstein cows. J. Dairy Sci. 75:1891. 19 Pike, B. V., and C. J. Roberts. 1980. The metabolic activity of bovine adipocytes before and after parturition. Res. Vet. Sci. 29: 108. 20 Poos, M. I., T. L. Hanson, and T. J. Klopfenstein. 1979. Monensin effects on diet digestibility, ruminal protein bypass and microbial protein synthesis. J. Anim. Sci. 48:1516. 21 Richardson, L. F., A. P. Raun, E. L. Potter, C. O. Cooley, and R. P. Rathmacher. 1976. Effect of monensin on rumen fermentation in vitro and in vivo. J. Anim. Sci. 43:657. 22 Sauer, F. D., J.K.G. Kramer, and W. J. Cantwell. 1989. Antiketogenic effects of monensin in early lactation. J. Dairy Sci. 72: 436. 23 Schelling, G. T. 1984. Monensin mode of action in the rumen. J. Anim. Sci. 58:1518. 24 Schmidt, F. H. 1961. Die enzymatische Bestimmung von Glucose und Fructose nebeneinander. Klin. Wochenchr. 39:1244.
MONENSIN AND PERIPARTURIENT METABOLISM 25 Shell, L. A., W. H. Hale, B. Theurer, and R. S. Swingle. 1983. Effects of monensin on total volatile fatty acid production by steers fed a high grain diet. J. Anim. Sci. 57:178. 26 Spears, J. W., B. R. Schricker, and J. C. Burns. 1989. Influence of lysocellin and monensin on mineral metabolism of steers fed forage-based diets. J. Anim. Sci. 67:2140. 27 Starnes, S. R., J. W. Spears, M. A. Froetschel, and W. J. Croom, Jr. 1984. Effect of monensin on total volatile fatty acid production by steers fed a high grain diet. J. Nutr. 114:518. 28 Stimson, C., R. C. Kellaway, R. J. Tassell, and R. L. Ison. 1991. Prediction of the nutrient content of botanical fractions from annual legumes by near-infrared reflectance spectroscopy. Grass Forage Sci. 46:99. 29 Suzuki, T., N. S. Agar, and M. Suzuki. 1985. Red blood cell metabolism in experimental animals: pentose phosphate pathway, antioxidant enzymes and glutathione. Exp. Anim. 34:353. 30 Thomas, E. E., S. E. Poe, R. K. McGuffey, and D. H. Mowrey. 1993. Effect of feeding monensin to dairy cows on milk produc-
837
tion and serum metabolites during early lactation. J. Dairy Sci. 76(Suppl. 1):280.(Abstr.) 31 Thomson, C., H. Rea, V. Doesburg, and M. Robinson. 1977. Selenium concentrations and glutathione peroxidase activities in whole blood of New Zealand residents. Br. J. Nutr. 37:457. 32 Trinder, N., C. D. Woodhouse, and C. Parenton. 1969. The effect of vitamin E and selenium on the incidence of retained placentae in dairy cows. Vet. Rec. 85:550. 33 Ullrey, D. E. 1987. Biochemical and physiological indicators of selenium status in animals. J. Anim. Sci. 65:1712. 34 Van Ryssen, J.B.J. 1991. Effect of monensin and its metabolites in broiler litter on sheep consuming the broiler litter. J. S. Afr. Vet. Med. Assoc. 62:94. 35 Vazquez-Anon, M., S. Bertics, M. Luck, R. R. Grummer, and J. Pinheiro. 1994. Peripartum liver triglyceride and plasma metabolites in dairy cows. J. Dairy Sci. 77:1521. 36 Zivan, J. A., and J. F. Snarr. 1973. An automated colorimetric method for the measurement of 3-hydroxybutyrate concentration. Anal. Biochem. 52:456.
Journal of Dairy Science Vol. 80, No. 5, 1997
ABSTRACT The effects of monensin on plasma concentrations and changes in plasma concentrations of energy metabolites and minerals over time were investigated using 24 multiparous Holstein cows. Cows were paired according to farm, predicted date of calving, and body condition score and were randomly allocated to two groups. Treated cows were given a ruminal bolus containing 32 g of monensin at 50 ± 7 d before predicted calving. Treated cows had lower plasma concentrations of glucose, free fatty acid (FFA), and b-hydroxybutyrate (BHBA) than did control cows before calving, indicating that monensin influenced energy metabolism. However, no significant differences in plasma concentrations of glucose, FFA, and BHBA were found between groups after calving. Plasma BHBA concentrations increased more before calving in control cows, and plasma FFA and urea concentrations increased significantly before calving in all cows. No significant differences in body weight, plasma concentrations of urea, or whole blood concentrations of glutathione peroxidase were detected between groups before or after calving. Plasma ceruloplasmin activity did not differ between groups before calving, but was significantly higher in treated cows after calving. Plasma concentrations of Ca did not significantly differ between groups before or after calving. Monensin altered both energy and mineral metabolism and has the potential to improve the health and production of dairy cows. ( Key words: monensin, metabolism, periparturient cows) Abbreviation key: Cp = ceruloplasmin, GSHPx = glutathione peroxidase. INTRODUCTION During early lactation, the mammary gland of dairy cows has a requirement for nutrients that is
Received September 29, 1995. Accepted September 13, 1996. 1997 J Dairy Sci 80:830–837
usually greater than that provided by feed intake. The consequent nutrient deficiency is met by partitioning nutrients from tissue stores and by mobilizing labile tissue reserves of lipid, protein, glycogen, and minerals. Uptake of glucose by the mammary gland during early lactation results in decreased plasma concentrations of glucose, which are strongly correlated with increased plasma concentrations of FFA and BHBA (18). Excessive mobilization of body tissue is associated with metabolic disorders such as ketonemia and fatty liver ( 6 ) . Administration of monensin may increase plasma concentrations of glucose (1, 10) by increasing ruminal propionate production ( 2 1 ) and possibly by mechanisms that are independent of ruminal function ( 2 ) . Increased glucose flux should decrease tissue mobilization and have beneficial impacts on the health and reproductive performance of cows. The requirement of mammary gland for minerals increases with the onset of lactation, and the sudden increase in demand for Ca is reflected in a marked decrease in plasma concentrations of Ca ( 1 4 ) and, in some cases, clinical hypocalcemia. Increased Ca demand is met by increased Ca absorption from the rumen and intestines and increased resorption from Ca stores in bone. Unfortunately, increased Ca flux from these sources is not evident until 24 to 48 h after calving (8, 9). Monensin increases the uptake of Ca from the intestines (26), influences the absorption of bivalent cations, and, therefore, may modify the risk or severity of parturient paresis. Similarly, absorption of Se ( 5 ) and Cu ( 3 4 ) is increased by monensin treatment. Deficiencies in Se have been associated with increased incidence of retained placenta ( 3 2 ) and uterine infection (12), and Se and Cu have important roles in antioxidant defense mechanisms. Increased availability of these minerals might modify the periparturient risk of disease for herds that are deficient in Se and Cu. Abe et al. ( 1 ) commenced monensin treatment of lactating cows in the period immediately after calving ( 1 ) , and Sauer et al. ( 2 2 ) commenced monensin treatment before calving. Those studies (1, 22) found
830
831
MONENSIN AND PERIPARTURIENT METABOLISM
All cows were fed on pasture. For nonlactating cows, the pasture consisted primarily of couch ( Cynodon dactylon) and kikuyu ( Pennisetum clandestinum) . After calving, all cows were fed pasture containing primarily kikuyu and ryegrass ( Lolium spp.). In addition, cows from one farm were fed pelleted concentrate at approximately 4 kg/d, and cows from the second farm were fed pellets at approximately 10 kg/d and 1 kg of hay beginning 2 wk before calving and when milking. The pelleted concentrates used on both farms were identical in formulation and included approximately 30% sorghum, 50% wheat bran and pollard, 8% meat meal, 8% cottonseed meal, 1% tallow, and 1% sodium bicarbonate to provide 18% CP. Feed samples were collected every 14 d and analyzed by near infrared reflectance spectroscopy using equations developed for local pastures and concentrates (28). Analyses of pasture and pellets are presented in Figures 1 and 2 and Table 1, respectively. All cows were weighed and scored for body condition every 14 d. The accuracy of the scales was verified by placing a known weight on the scales before and after weighing. The standard error was < ±5 kg. Body condition was scored using 0.25 increments ( 1 = thin to 5 = obese) ( 7 ) . Blood (25 ml) was taken weekly from the coccygeal vessels using vacutainers (Becton-Dickinson Vacutainer Systems, Rutherford, NJ). The last blood samples were taken 3 wk after calving. The blood was transported on ice before centrifugation, decanting, and storage at –20°C for later analyses. Enzymatic colorimetric methods were used to determine glucose (24), BHBA (36), FFA (NEFA-C; Wako Pure Chemicals Industries, Ltd., Osaka, Japan), plasma urea (11), GSHPx (32), and Cp activities (13). Plasma Ca was determined by atomic absorption spectroscopy (Varian Spectra AA-20; Varian Techtron, Pty. Ltd., Melbourne, Victoria, Australia).
higher plasma concentrations of glucose and lower plasma concentrations of ketones and FFA after calving. The goal of this study was to evaluate the effects of monensin administered in a controlled-release capsule on metabolic and mineral responses of cows during the periparturient period. Because feed intake can be depressed shortly after monensin treatment (23), we administered the capsules early in the dry period when nutritional requirements are lower. Our hypothesis was that monensin administration would increase plasma concentrations of glucose, ceruloplasmin ( Cp) , glutathione peroxidase ( GSHPx) , and Ca and decrease plasma concentrations of FFA, urea, and BHBA. This study examined the impact of monensin capsules that were administered during the dry period at 50 d before expected calving on metabolism of dairy cows and evaluated the periods when treatment effects of monensin were likely to be the greatest. MATERIALS AND METHODS Twenty-four multiparous Holstein-Friesian cows from two farms were used in the study, which was conducted over a 12-wk period during autumn in New South Wales, Australia. Cows entered the trial at 50 ± 7 d before predicted calving. Upon entering the trial, cows were paired according to body condition score, calving date, and farm before being allocated randomly into treatment groups. The operators handling the cows were unaware of treatment allocation. The control group was given a sham treatment (the gun used for capsule administration was placed in the mouth of the cow and was discharged), and the treatment group was given one capsule of controlledrelease monensin (Rumensin Antibloat Capsule; Elanco Animal Health, West Ryde, New South Wales, Australia) orally. The capsules contained 32 g of monensin, which was released at 300 mg/d over approximately 100 d.
TABLE 1. Analysis of concentrate hay and pellets.1 Energy
CP
ME2
Hay Pellets
(MJ of X 7.64 12.254
of DM/kg) SD 0.31
X 10.53 19.02
SD 4.74 0.51
Crude fiber ( % of DM) X SD NA3 9.85 1.37
Fat X NA 6.67
SD 0.33
1Means
for seven pellet and two hay analyses. energy. 3Not available. 4Estimated from crude fiber, CP, and fat. 2Metabolizable
Journal of Dairy Science Vol. 80, No. 5, 1997
832
STEPHENSON ET AL.
Figure 1. Metabolizable energy ( M E ) content of pastures during the trial. Legend: ⁄ = pasture fed to dry cows on farm 1, ÿ = pasture fed to dry cows on farm 2, ♦ = pasture fed to lactating cows on farm 1, and … = pasture fed to lactating cows on farm 2.
outcome variables did not differ over time, and that the pattern of change in variables between treatment groups over time was not different. The effects of farm, interval from treatment to calving, and pretreatment differences between group values were adjusted for using covariables. Power calculations on the results analyzed by repeated measures were made using SOLO Statistical System Power Analysis (BMDP Statistical Software Inc.). Significance was tested at P ≤ 0.1 because of the relatively small number of cows used in the study. Thus, the statistical power in this study was relatively low. Plasma BHBA had the largest difference between means, and the coefficient of variation was low; the power to evaluate the difference in means was greatest for this variable. The power to evaluate the difference of 24% in means for plasma BHBA differences between treatments, treatment by time effects (differences between groups in the pattern of change in BHBA over time), and change in BHBA over time was 0.30, 0.59, and 0.85, respectively. RESULTS AND DISCUSSION
Body weight and plasma concentrations of glucose, FFA, BHBA, plasma urea, Cp, GSHPx, and Ca were assessed by repeated measures of variance with covariables (BMDP 2V; BMDP Statistical Software Inc., Los Angeles, CA). The covariables were farm, interval from treatment to calving, and pretreatment values of the variables. Because the direction of some responses varied before and after calving and because 1 cow died of milk fever at calving, data before and after calving were analyzed separately, except for BW data. Because of the variation in time to calving, some values between 50 and 35 d before calving were missed; consequently, only data collected from blood analysis between 35 d before calving and 14 d after calving were analyzed. Plasma Ca determinations were made on samples collected before treatment and between 14 d before and 14 d after calving. Body weight data were collected every 14 d and were evaluated for the period between 28 d before and 14 d after calving. Missing values were extrapolated or interpolated to allow analysis, and one extrapolated value each was needed for data for the FFA, BHBA, Cp, and GSHPx. Plasma urea and glucose required one extrapolated and one interpolated value, and BW required one extrapolated and four interpolated values. The effects of treatment, time, and treatment by time effects (differences between treatment groups in change of variables over time) were tested. The null hypotheses examined were that the effect of treatment on outcome variables was not significant, that Journal of Dairy Science Vol. 80, No. 5, 1997
Although Sauer et al. ( 2 2 ) commenced monensin treatment before calving, we could find no previously published data on the effects of monensin in dry cows. The mean interval from treatment to calving was 50.3 ± 6.9 d. For all cows, plasma concentrations of glucose (Figure 3 ) remained stable ( P = 0.73), and plasma concentrations of FFA (Figure 4 ) increased ( P =
Figure 2. Crude protein content of pastures during the trial. Legend: ⁄ = pasture fed to dry cows on farm 1, ÿ = pasture fed to dry cows on farm 2, ♦ = pasture fed to lactating cows on farm 1, and … = pasture fed to lactating cows on farm 2.
MONENSIN AND PERIPARTURIENT METABOLISM
833
Figure 3. Mean plasma glucose concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
Figure 5. Mean plasma BHBA concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
0.001), as calving approached. Plasma concentrations of BHBA (Figure 5 ) tended to increase ( P = 0.11) for both groups, but concentrations increased more ( P = 0.05) for control cows as calving approached. These findings of increased plasma concentrations of FFA and BHBA and relatively stable glucose concentrations immediately prior to calving for cows fed diets based on pasture were very similar to those results found by Vazquez-Anon et al. ( 3 5 ) for cows that were
fed rations based on hay and silage in herds under housed conditions. In our study, plasma glucose concentrations were lower ( P = 0.10) in treated cows than in control cows before calving. Previous studies (1, 10), however, have identified significant increases in blood concentrations of glucose in cows treated with monensin after calving (1, 10), which initially appear to be inconsistent with the glucogenic action of monensin. However, increased glucogenic flux might have stimulated the release of insulin and resulted in lower plasma concentrations of glucose in treated cows, perhaps from an increased partitioning of glucose to the rapidly growing fetus ( 4 ) . Increased birth weight of calves born to cows treated with monensin before calving has been reported (N. B. Williamson, 1996, unpublished data). A decrease in glucose concentrations is also consistent with reduced rates of lipogenesis for bovine adipocytes harvested after calving compared with those harvested before calving ( 1 9 ) and with the lower sensitivity of adipocytes harvested after calving to insulin ( 3 ) . However, partitioning of glucose to adipose tissue would be a minor effect of the limited role of glucose in ruminant adipose synthesis. Treated cows had lower plasma concentrations of FFA ( P = 0.06) and BHBA ( P = 0.08) before calving, a result that is consistent with changes in those metabolites after calving that have been reported in other studies (1, 22, 30). The lower concentrations of plasma BHBA and FFA might have resulted from several actions of monensin, including a decrease in the ruminal acetate to propionate ratio (21), which
Figure 4. Mean plasma FFA concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
Journal of Dairy Science Vol. 80, No. 5, 1997
834
STEPHENSON ET AL.
Figure 6. Mean plasma urea concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
subsequently increased hepatic oxidation of glucose in the TCA cycle; a decrease in ruminal production of butyrate (25), which reduced dietary entry of BHBA precursors; a glucogenic effect that was independent of ruminal function modification ( 2 ) ; reduced demand for FFA mobilization as a result of increased glucose availability; or decreased ruminal degradation of dietary protein (20), which increased amino acid availability for gluconeogenesis. However, no differences in plasma urea concentrations (Figure 6 ) were detected between treatment groups before ( P = 0.85) or after ( P = 0.18) calving, possibly indicating that any increase in the available protein was negligible or that the measurement of plasma concentrations of urea was not sufficiently sensitive to detect differences in protein metabolism between the groups. Plasma concentrations of urea ( P = 0.001), increased before calving in association with greater protein availability in rations and body tissue mobilization in a manner similar to the increase in FFA concentrations. Body weights decreased over time ( P = 0.001) for all cows (Figure 7), but no differences in BW were found between treatment groups ( P = 0.47). After calving, glucose concentrations did not differ between treatment groups ( P = 0.73), a finding that was consistent with the results of Sauer et al. ( 2 2 ) but not with those of Abe et al. ( 1 ) , who found higher glucose concentrations in cows treated with monensin. Sauer et al. (22), however, noted that plasma concentrations of glucose were higher in cows treated with monensin, and the power to determine differJournal of Dairy Science Vol. 80, No. 5, 1997
ences between groups in that study was low. Monensin might have increased glucose availability, but high demands for glucose by the mammary gland of the lactating cow kept plasma concentrations relatively constant. Most studies investigating changes in energy metabolites in the periparturient period have evaluated plasma concentrations of metabolites after calving. In the present study, the pattern of change in plasma concentrations of glucose, FFA, and BHBA after calving was typical of that previously found in studies by Abe et al. ( 1 ) and Lean et al. ( 1 8 ) in which plasma concentrations of glucose declined and plasma concentrations of BHBA and FFA increased. No differences were detected in mean plasma concentrations of FFA ( P = 0.45) and BHBA ( P = 0.32) or changes in plasma concentrations of FFA ( P = 0.74) and BHBA ( P = 0.65) between groups after calving, although plasma concentrations of FFA and BHBA were lower in the treated cows. Other studies (1, 22) have reported decreased plasma concentrations of FFA and BHBA in cows treated with monensin. In this study, plasma concentrations of FFA and BHBA before and after calving suggest that FFA mobilization and BHBA production were reduced, but the statistical power of the study was insufficient to detect changes in the concentrations of these metabolites after calving. The GSHPx activity (Figure 8 ) tended to increase ( P = 0.11) prior to calving. Whole blood concentra-
Figure 7. Mean BW of treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
MONENSIN AND PERIPARTURIENT METABOLISM
Figure 8. Mean blood glutathione peroxidase concentrations [in hemoglobin (Hb)] in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
tions of GSHPx did not differ between treatment groups before ( P = 0.98) or after ( P = 0.98) calving, nor did the pattern of change differ before or after calving ( P = 0.83 and P = 0.13, respectively). On both farms used in the study, GSHPx activity was low (29), which indicated Se deficiency (33), despite considerable interlaboratory variation in GSHPx assay methods (17). The GSHPx present in blood is predominantly present in erythrocytes, which remain in circulation for approximately 100 d. Whole blood concentrations of GSHPx, therefore, reflect Se intake over the previous 100 d and may not reflect immediate changes in the availability of Se. Although Costa et al. ( 5 ) found that Se uptake was increased by monensin administration in steers, Vay Ryssen ( 3 4 ) found no significant difference in blood concentrations of GSHPx between cows treated with monensin and control cows. Horvath et al. (15), however, found significant increased in blood concentrations of GSHPx in pigs within 28 d of the commencement of monensin administration, indicating the potential for monensin supplementation to modify Se metabolism and GSHPx activity over a relatively short period. Plasma Cp activity (Figure 9 ) did not differ between treatment groups before calving ( P = 0.87) but was higher in treated cows after calving ( P = 0.04). Changes over time in plasma Cp activity were not different between groups before ( P = 0.85) or after ( P = 0.34) calving. The increase in Cp that occurred in treated cows after calving might reflect an improved capacity of treated cows to mobilize Cp, an acute
835
Figure 9. Mean ceruloplasmin concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements.
phase protein that is important in controlling oxidative challenge from free radicals. Ceruloplasmin is an accurate measure of Cu status when Cu supply is deficient because Cp-binding sites are unsaturated at a low Cu intake. Cows in this trial might have been deficient in Cu because soils in the area are deficient in Cu ( 1 6 ) and the farms did not provide supplemental Cu. Van Ryssen ( 3 4 ) demonstrated that monensin increased Cu activity in the liver of sheep by using
Figure 10. Mean plasma Ca concentrations in treated ( ⁄) and untreated ( …) cows. pretrt = Pretreatment measurements. Journal of Dairy Science Vol. 80, No. 5, 1997
836
STEPHENSON ET AL.
liver biopsies, a more sensitive measure of Cu status than Cp. Our results support the findings of Van Ryssen (34), indicating a potential for monensin to improve Cu absorption. Mean plasma concentrations of Ca (Figure 10) did not differ between treatment groups before ( P = 0.99) or after ( P = 0.62) calving. Plasma Ca decreased ( P = 0.001) as cows neared parturition, which was consistent with results of other studies (14), and there was a difference ( P < 0.001) between groups in the pattern of change in plasma concentrations of Ca; control cows maintained more constant concentrations of Ca in plasma. Previous work with steers (26, 27) has found that Ca absorption increased after monensin treatment. Because 1 treated cow died of milk fever, the effect of monensin treatment on the risk of hypocalcemia and related disorders should be examined in large randomized clinical trials. Our study found differences between treated cows and control cows in concentrations of glucose, BHBA, and FFA and in Cp and Ca metabolism during the period of adaptation to lactation. The study also identified times when plasma metabolites were likely to differ between treatment groups. The decreased plasma concentrations of glucose prior to calving in treated cows probably reflect greater glucose availability and loss to the fetus. The reduction in plasma concentrations of FFA and BHBA should act to reduce the risk of metabolic disorders related to lipid mobilization after calving. Increased Cp activity indicated enhanced Cu absorption and a greater potential for control of oxidative challenge. Further studies should be conducted to explore the potential for monensin to modify both the metabolic adaptive responses of dairy cows to lactation and to examine the effects of monensin on health, reproduction, and production on a population basis. ACKNOWLEDGMENTS The authors thank John McClure, the late Christine Gerard, Diane Ryan, and Nancy Kelly for technical assistance and Elanco Animal Health, West Ryde, New South Wales, Australia, for financial support. REFERENCES 1 Abe, N., I. J. Lean, A. Rabiee, J. Porter, and C. Graham. 1994. Effects of sodium monensin on reproductive performance of dairy cattle. II. Effects on metabolites in plasma, resumption of ovarian cyclicity and oestrus in lactating cows. Aust. Vet. J. 71: 277. 2 Armstrong, J. D., and J. W. Spears. 1988. Intravenous administration of ionophores in ruminants: effects on metabolism independent of the rumen. J. Anim. Sci. 66:1807. Journal of Dairy Science Vol. 80, No. 5, 1997
3 Baldwin, R. L., and N. E. Smith. 1971. Intermediary aspects and tissue interactions of ruminant fat metabolism. J. Dairy Sci. 54:583. 4 Bell, A. W. 1995. Regulation of organic nutrient metabolism during transition from late pregnancy to early lactation. J. Anim. Sci. 73:2804. 5 Costa, N. D., P. T. Gleed, B. F. Sanson, H. W. Symonds, and W. M. Allen. 1985. Monensin and narasin increase selenium and zinc absorption in steers. Page 472 in Trace Element Metabolism in Man and Animals. C. F. Mills, I. Bremner, and J. K. Chesters, ed. Commonw. Agric. Bur., Slough, England. 6 Dohoo, I. R., and S. W. Martin. 1984. Subclinical ketosis: prevalence and associations with production and disease. Can. J. Comp. Med. 48:1. 7 Edmondson, A. J., I. J. Lean, L. D. Weaver, T. Farver, and G. Webster. 1989. A body condition scoring chart for Holstein dairy cattle. J. Dairy Sci. 72:68. 8 Goff, J. P., R. L. Horst, E. T. Littledike, A. Boris, and M. R. Uskokovic. 1986. Bone resorption, renal function and mineral status in cows treated with 1,25-dihydroxy-cholecalciferol and its 24-fluro analogues. J. Nutr. 116:150. 9 Goff, J. P., E. T. Littledike, and R. L. Horst. 1986. Effect of synthetic bovine parathyroid hormone in dairy cows: prevention of hypocalcemic parturient paresis. J. Dairy Sci. 69:2278. 10 Grings, E. E., and J. R. Males. 1987. Performance, blood and ruminal characteristics of cows receiving monensin and a magnesium supplement. J. Anim. Sci. 66:566. 11 Gutman, N. I., and H. U. Bergmeyer. 1974. Urea. Page 1791 in Methods of Enzymatic Analysis. 2nd ed. Vol. 4. Acad. Press, New York, NY. 12 Harrison, J. H., D. D. Hancock, N. St. Pierre, H. R. Conrad, and W. R. Harvey. 1986. Effect of selenium treatment on uterine involution in the dairy cow. J. Dairy Sci. 69:1421. 13 Henry, R. J., N. Chiamori, S. L. Jacobs, and M. Segalove. 1960. Determination of ceruloplasmin oxidase in serum. Proc. Soc. Exp. Biol. Med. 104:620. 14 Horst, R. L. 1986. Regulation of calcium and phosphorus homeostasis in the dairy cows. J. Dairy Sci. 69:604. 15 Horvath, C. J., H. D. Stowe, and E. R. Miller. 1992. Effects of monensin on selenium status and related factors in genetically hypo- and hyperselenemic growing swine. Am. J. Vet. Res. 53: 2109. 16 Kellaway, R. C., R. J. Tassell, E. Havilah, N. Sriskandarajah, and A. Andrews. 1993. Nutrient balance in the diet of grazing dairy cows. Aust. J. Agric. Res. 44:423. 17 Langlands, J. P., J. F. Wilkins, J. E. Bowles, A. J. Smith, and R. F. Webb. 1981. Selenium concentration in the blood of ruminants grazing in northern NSW. I. Analysis of samples collected in the national brucellosis eradication scheme. Aust. J. Agric. Res. 32:511. 18 Lean, I. J., T. B. Farver, H. F. Troutt, M. L. Bruss, J. C. Galland, R. L. Baldwin, C. A. Holmberg, and L. D. Weaver. 1992. Time series cross-correlation analysis of postparturient relationships among serum metabolites and yield variables in Holstein cows. J. Dairy Sci. 75:1891. 19 Pike, B. V., and C. J. Roberts. 1980. The metabolic activity of bovine adipocytes before and after parturition. Res. Vet. Sci. 29: 108. 20 Poos, M. I., T. L. Hanson, and T. J. Klopfenstein. 1979. Monensin effects on diet digestibility, ruminal protein bypass and microbial protein synthesis. J. Anim. Sci. 48:1516. 21 Richardson, L. F., A. P. Raun, E. L. Potter, C. O. Cooley, and R. P. Rathmacher. 1976. Effect of monensin on rumen fermentation in vitro and in vivo. J. Anim. Sci. 43:657. 22 Sauer, F. D., J.K.G. Kramer, and W. J. Cantwell. 1989. Antiketogenic effects of monensin in early lactation. J. Dairy Sci. 72: 436. 23 Schelling, G. T. 1984. Monensin mode of action in the rumen. J. Anim. Sci. 58:1518. 24 Schmidt, F. H. 1961. Die enzymatische Bestimmung von Glucose und Fructose nebeneinander. Klin. Wochenchr. 39:1244.
MONENSIN AND PERIPARTURIENT METABOLISM 25 Shell, L. A., W. H. Hale, B. Theurer, and R. S. Swingle. 1983. Effects of monensin on total volatile fatty acid production by steers fed a high grain diet. J. Anim. Sci. 57:178. 26 Spears, J. W., B. R. Schricker, and J. C. Burns. 1989. Influence of lysocellin and monensin on mineral metabolism of steers fed forage-based diets. J. Anim. Sci. 67:2140. 27 Starnes, S. R., J. W. Spears, M. A. Froetschel, and W. J. Croom, Jr. 1984. Effect of monensin on total volatile fatty acid production by steers fed a high grain diet. J. Nutr. 114:518. 28 Stimson, C., R. C. Kellaway, R. J. Tassell, and R. L. Ison. 1991. Prediction of the nutrient content of botanical fractions from annual legumes by near-infrared reflectance spectroscopy. Grass Forage Sci. 46:99. 29 Suzuki, T., N. S. Agar, and M. Suzuki. 1985. Red blood cell metabolism in experimental animals: pentose phosphate pathway, antioxidant enzymes and glutathione. Exp. Anim. 34:353. 30 Thomas, E. E., S. E. Poe, R. K. McGuffey, and D. H. Mowrey. 1993. Effect of feeding monensin to dairy cows on milk produc-
837
tion and serum metabolites during early lactation. J. Dairy Sci. 76(Suppl. 1):280.(Abstr.) 31 Thomson, C., H. Rea, V. Doesburg, and M. Robinson. 1977. Selenium concentrations and glutathione peroxidase activities in whole blood of New Zealand residents. Br. J. Nutr. 37:457. 32 Trinder, N., C. D. Woodhouse, and C. Parenton. 1969. The effect of vitamin E and selenium on the incidence of retained placentae in dairy cows. Vet. Rec. 85:550. 33 Ullrey, D. E. 1987. Biochemical and physiological indicators of selenium status in animals. J. Anim. Sci. 65:1712. 34 Van Ryssen, J.B.J. 1991. Effect of monensin and its metabolites in broiler litter on sheep consuming the broiler litter. J. S. Afr. Vet. Med. Assoc. 62:94. 35 Vazquez-Anon, M., S. Bertics, M. Luck, R. R. Grummer, and J. Pinheiro. 1994. Peripartum liver triglyceride and plasma metabolites in dairy cows. J. Dairy Sci. 77:1521. 36 Zivan, J. A., and J. F. Snarr. 1973. An automated colorimetric method for the measurement of 3-hydroxybutyrate concentration. Anal. Biochem. 52:456.
Journal of Dairy Science Vol. 80, No. 5, 1997