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Effect of Gold Thioglucose on Survival, Feed Consumption and Body Weight of Broilers
ISOLEUCINE, VALINE AND LEUCINE tabolism and pregnancy of the rat as affected by dietary supplementations with leucine and other amino acid mixtures. J. Nutr. 100: 51-58. Mathieu, D. M., 1968. Amino acid imbalance versus amino acid antagonism in the chick. M.S. Thesis. University of Illinois, Urbana, Illinois. Miller, E. C , M. L. Sunde, H. R. Bird and C. A. Elvehjem, 1954. The isoleucine requirement of the laying hen. Poultry Sci. 33 : 1201-1209. Nelson, O. E., E. T. Mertz and L. S. Bates, 1965. Second mutant gene affecting the amino acid pattern of maize endosperm proteins. Science, 150:1469-1470.
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Raghuramula, N., B. S. N. Rao and C. Gopalan, 1965. Amino acid imabalance and tryptophanniacin metabolism I. Effect of excess leucine on the urinary excretion of tryptophan-niacin metabolites in rats. J. Nutr. 86: 100-106. Tannous, R. I., Q. R. Rogers and A. E. Harper, 1966. Effect of leucine-isoleucine antagonism on the amino acid pattern of plasma and tissues of the rat. Arch. Biochem. Biophys. 113: 356361. Zimmerman, R. A., D. C. Snetsinger, D. W. Cardin and D. E. Greene, 1969. Amino acid imbalances in practical poultry diets. Poultry Sci. 48: 1894.
K. L. SIMKINS AND J. M. PENSACK Agricultural Division, American Cyanamid Company, Princeton, N.J. 08540 (Received for publication May 4, 1970) INTRODUCTION
W
AXLER and Brecher (1950) reported that about one-third of the stock albino mice that survived a single LD50 dose of gold thioglucose (GTG) developed varying degrees of hyperphagia and obesity. Marshall et al. (1955) found that the GTG induced obesity in mice was associated with lesions in the ventromedial nuclei in the hypothalamus. Liebelt and Perry (1957) reported that GTG produced different degrees of hypothalamic damage and obesity in two genetically independent inbred strains of mice. At the time the present study was initiated, there were no reports concerning the effect of GTG on fowl. Recently, Carpenter et al. (1969) reported that feed consumption, body weight and reproduction of Japanese quail were not affected by GTG treatment. Carpenter et al. (1969) did not find any evidence of destruction in either the hypothalamus or amygdala in GTG treated quail. The objectives of the present study
were: (1) to determine the approximate LD50 dose of a single intramuscular GTG injection in five day old broiler chicks, (2) to determine the effect of GTG on feed consumption and weight gain by broilers, and (3) to compare the effects of GTG in mice and broilers. MATERIALS AND METHODS
Peterson-Cross broiler chicks (Kerr Chickeries, Frenchtown, N.J.) were housed in wire batteries in a room where the heat was thermostatically controlled. The chicks had access to water and the ration shown in Table 1 at all times. Each chick was weighed and identified prior to injection. Gold thioglucose (Schering Corp., Bloomfield, N.J.) suspended in sesame oil was injected into the leg muscle when the chicks were 5 days old. The quantity of GTG injected was 1.0 and 0.5 mg./g. of body weight in Experiments 1 and 2, respectively. Control chicks were injected with a solution composed of 10% polyethylene glycol, 0.81% sodium chloride,
Downloaded from http://ps.oxfordjournals.org/ at University of North Dakota on May 17, 2015
Effect of Gold Thioglucose on Survival, Feed Consumption and Body Weight of Broilers
1342
K . L . SlMKINS AND J . M . PENSACK TABLE 1.—Composition of Broiler Ration Ingredient
Ground yellow corn Soybean meal (50% protein) Corn gluten meal Menhaden fish meal (60% protein) Stabilized fat Dehydrated alfalfa meal Ground limestone (33% Ca) Dicalcium phosphate Sodium chloride Trace minerals1 Vitamin premix2
53.4 28.0 5.0 5.0 4.0 2.0 0.5 1.2 0.3 0.1 0.5 100.0
1 Provided 60p.p.m. manganese, 20p.p.m. iron, 20 p.p.m. zinc, 2 p.p.m. copper, 12 p.p.m. iodine, and 0.2 p.p.m. cobalt, in ration. 2 Provided 3,300I.U. vitamin A, 1,1001.U. vitamin D3, 2.2 I.U. vitamin E, 500 mg. choline chloride, 500 mg. DL-methionine, 125 mg. ethoxyquin, 27.5 mg. niacin, 8.8 mg. pantothenic acid, 4.4 mg. riboflavin, 1.43 mg. folic acid, 1.1 mg. menadione, 0.011 mg. vitamin B12 per kilogram of feed.
0.45% carboxymethylcellulose and 0.36% Tween 80 in distilled water. In both experiments, 60 chicks (30 males, 30 females) received the control and GTG injections. In Experiment 1, the chicks were kept in groups of 15 until two days postinjection when the chicks that survived the injection of 1 mg. GTG/g. body weight were placed in individual pens. Control birds that had initial body weights similar to those of the surviving GTG injected birds were also placed in individual pens. The chicks were housed in individual pens for 12 weeks and then sacrificed. Body weights and feed consumptions were recorded every other day during the first six weeks and at weekly intervals thereafter. In Experiment 2, the chicks were kept in groups of 15 until four days postinjection when the chicks that survived the injection of 0.5 mg. GTG/g. body weight were placed on either Experiment 2A or 2B. In Experiment 2A, the twelve week performance of group fed GTG injected and control chicks was compared. There were two pens having four male chicks and two pens
RESULTS AND DISCUSSION
The survival of five day old broiler chicks that received a single intramuscular injection of 1.0 mg. GTG/g. of body weight is shown in Table 2. A total of 56 out of 60 chicks died within 48 hours post-injection. One of the four chicks that survived died 33 days later. The twelve week weight gains and feed consumptions by the three chicks that survived did not appear to be
Downloaded from http://ps.oxfordjournals.org/ at University of North Dakota on May 17, 2015
Total
Percent
having four female chicks for both the control and GTG treatments. The biweekly weight gains and feed consumptions by each pen of birds were analyzed for statistical significance using a factorial design as outlined by Steel and Torrie (1960). In addition, individual bird weights were recorded biweekly. In Experiment 2B, 21 GTG injected birds (11 males, 10 females) were individually fed for a six week period. Since cage space was limited, only four control males and females were individually fed. The six week body weights, feed consumptions, and feed efficiencies were analyzed for statistical significance using a t test with unequal replications as outlined by Steel and Torrie (1960). Experiment 3 was conducted with 60 six week old white female mice, CF1, obtained from Carworth Laboratories. The mice were individually housed in an air-conditioned room (22°C.) and received a commercial mouse ration and water ad libitum. GTG was injected into 50 of the mice at a level of 1.0 mg./g. of body weight and 10 mice received the control injection previously described for chicks. Feed consumption and body weight of each mouse were recorded at weekly intervals for a twelve week period. Terminal body weights and feed consumption by control and GTG treated mice were compared using a t test (Steel and Torrie, 1960).
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EFFECT OF GOLD THIOGLUCOSE
TABLE 4.—Analysis of variance of mean body weights and feed consumption by group fed broilers in Experiment 2A
TABLE 2.—Survival of five day old broiler chicks after receiving a single intramuscular injection of gold thioglucose
Body weights
Survivors/Total
Exp. No.
mg. GTG/g. body wt.
Males
Females
1 2
1.0 0.5
3/30 19/30
1/30 18/30
variation
TABLE 3.—Effect of gold thioglucose on mean body weights (g.) and feed consumption (g./bird) by group fed broilers in Experiment 2A Item
Days Postinfection
No. of birds" Body weight
Feed intake
a
Males Control
Females , G T
G T Q
Contro
Degrees of freedom
Mean squares
6 1 1 6 6 1 6 1 27
8,215,029** 1,108,265** 12,479 170,969** 6,622 7 5,928 36,719 11,558
5 1 1 5 5 1 5 1 23
2 ,320,330** 644,033** 4,485 45,269** 7,432 15,768 2,963 72,385** 4,676
** P < . 0 1 .
GTG did not have any effect on feed consumptions or body weights throughout the twelve week feeding period. The mean body weights and feed consumptions by individually fed chicks in Experiment 2B are shown in Table 5. There were no significant differences between the body weights and feed consumptions of the GTG treated and control birds. The injection of 0.5 mg. GTG/g. body weight did not significantly (P > .10) affect the feed conversion (g. feed/g. gain) in Experiments 2A and 2B. In Experiment 3, 18 out of 50 six week old mice that received a single intramuscular injection of 1.0 mg. GTG/g. body weight died. The twelve week body weights and feed consumptions by the mice that survived are presented in Table 6. When all 32 surviving GTG injected mice are compared to the 10 control mice, the difference in body weight gain is significant (P <
G
8
8
8
8
0 14 28 42 56 70 84
75 338 798 1,364 2,048 2,617 3,109
74 300 780 1,345 2,034 2,370 3,232
80 341 719 1,164 1,612 2,068 2,391
74 298 695 1,094 1,613 2,035 2,363
5-14 15-28 29-42 43-56 57-70 71-84
296 867 1,111 1,542 1,778 1,740
275 879 1,148 1,549 1,884 1,934
281 736 958 1,244 1,444 1,499
258 746 926 1,201 1,342 1,587
One G T G treated male and one G T G treated female died during the experiment.
TABLE 5.—Effect of gold thioglucose on mean body weights and feed consumption {g./bird) by individually fed broilers in Experiment 2B Item
Days postinfection
Males Control
Feed intake
Control
GTG
10
No. of birds Body weight
Females
GTG
10
0 14 28 42
73 323 767 1,203
70 275 746 1,211
76 318 709 1,129
73 285 680 1,103
5-14 15-28 29-42
339 961 1,240
295 880 1,245
326 891 1,109
307 809 1,095
Downloaded from http://ps.oxfordjournals.org/ at University of North Dakota on May 17, 2015
significantly different from those of control chicks. However, the small numbers of chicks involved make any conclusions unwarranted. The survival of broiler chicks that received 0.5 mg. GTG/g. body weight is shown in Table 2. A total of 37 out of 60 chicks survived. There were no differences between the sexes with regard to GTG toxicity. The mean body weights and feed consumptions by group fed chicks in Experiment 2 A are presented in Table 3. An analysis of variance of the body weight and feed consumption data obtained in Experiment 2 A is presented in Table 4. The body weights and feed consumptions by the GTG treated chicks were not significantly different (P > .01) from those by control chicks. There were no significant period by treatment interactions which indicates that
Periods (A) Sex (B) Treatments (C) AXB AXC BXC AXBXC Replicates Error
Feed consumption
Mean squares
Degrees ol: freedom
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K . L. SlMKINS AND J . M . PENSACK
TABLE 6.—Effect of gold thioglucose on body weights and feed consumption by mice in Experiment 3
Control
10 32 (10)* (9) (13)
GTG
12-Week weight • range (g-)
Mean 12 week mouse values Gain (g.)
Feed consump. (g.)
24-33
5.2
435
24-58 46-58 38-44 24-35
16.8 27.9 18.6 7.2
472 537 467 427
a Values in parentheses represent arbitrary breakdown of GTG treated mice into obese, intermediate and non-obese groups.
.01). However, the difference between the feed consumed by the 32 GTG injected mice and the 10 control mice is not statistically significant (P > .10). Since Marshall et al. (1955) reported that non-obese mice weighed 25 to 35 g. and obese mice weighed 45 g. or more, the mice injected with GTG in Experiment 3 were separated into obese, intermediate and nonobese groups on the basis of their body weights (Table 6). The results show that 10 out of 32 GTG injected mice would be considered obese. These results confirm the reports by other workers (Breecher and Waxier, 1949; Waxier and Breecher, 1950) that about one-third of the albino mice that survive a single LD 50 dose of GTG develop obesity. The weight gain and feed consumption by the 10 obese mice were significantly (P < .01) greater than those of the 10 control mice. The results of Experiment 3 demonstrated that some mice are markedly affected by GTG injection, whereas other mice do not appear to be different from controls. Because it was possible that some individual chicks may have been affected by the GTG injection, the ranges in body weights of GTG injected chicks were compared to those of control chicks (Table 7). The data in Table 7 indicates that none of
TABLE 7.—Comparison of ranges of body weights (g.) of control and gold thioglucose treated broilers
Exp.
Weeks postinjection
2A
6
Male 1,174-1,474 Female 1,098-1,249
1,154-1,452 1,010-1,233
12
Male 2,704-3,574 Female 1,972-2,647
2,803-3,575 2,224-2,518
6
Male 1,157-1,249 Female 1,003-1,207
1,129-1,280 930-1,245
2B
C
^
j ., K
Control
GTG
Downloaded from http://ps.oxfordjournals.org/ at University of North Dakota on May 17, 2015
Treatment
No. of
the chicks injected with 0.5 mg. GTG/g. body weight had significantly greater body weights than the control chicks. The percent mortality produced by the injection of 1.0 mg. GTG/g. body weight in mice was very similar to that produced by the injection of 0.5 mg. GTG/g. body weight in chicks (36 and 38%, respectively). Since approximately one-third of the surviving mice developed hyperphagia, it appears that the GTG dosage given to chicks would have been sufficient to produce hyperphagia in a few survivors if GTG had a similar effect on mice and chicks. Since none of the GTG injected chicks exhibited hyperphagia and increased body weight, it was concluded that a single intramuscular injection of 0.5 mg. GTG/g. body weight in five day old Peterson-Cross chicks does not affect weight gain and feed consumption by surviving birds. The results of the chick experiments agree with the results of the Japanese quail experiments reported by Carpenter et al. (1969). These workers found that a single intramuscular GTG injection did not affect the feed consumption, body weight or reproduction by Japanese quail. Carpenter et al. (1969) were unable to find any histological evidence that GTG damages the hypothalamus in Japanese quail. Marshall et al. (1959) showed that hyperphagia and obesity occurred only in those mice that
EFFECT OF GOLD THIOGLUCOSE
SUMMARY
The survival of five day old PetersonCross broiler chicks that received a single intramuscular injection of 0.5 and 1.0 mg. GTG/g. body weight was 62 and 7%, respectively. The body weights and feed con-
sumptions by chicks that survived the injection of 0.5 mg. GTG/g. body weight were not significantly (P < .05) different from those of control chicks at either 6 or 12 weeks postinjection. The survival of six week old white mice injected with 1.0 mg. GTG/g. body weight was 64%. Hyperphagia and obesity were observed in approximately one-third of the survivors. REFERENCES Brecher, G., and S. H. Waxier, 1949. Obesity in albino mice due to single injections of goldthioglucose. Proc. Soc. Exp. Biol. Med. 70: 498-501. Carpenter, J. W., C. M. Stein, A. Silverstein and A. van Tienhoven, 1969. The effect of gold thioglucose on food consumption and reproduction of the Japanese quail {Coturnix Coturmx Japonica). Poultry Sci. 48: 574-578. Liebelt, R. A., and J. H. Perry, 19S7. Hypothalamic lesions associated with gold thioglucose-induced obesity. Proc. Soc. Exp. Biol. Med. 95: 774-777. Marshall, N. B., R. J. Barnett and J. Mayer, 1955. Hypothalamic lesions in gold thioglucose injected mice. Proc. Soc. Exp. Biol. Med. 90: 240-244. Steel, R. G. D., and J. H. Torrie, 1960. Principles and Procedures of Statistics. McGraw-Hill Book Co., Inc., New York, N.Y. Talbert, G. B., and J. B. Hamilton, 1954. Failure to produce obesity in the rat following gold thioglucose injection. Proc. Soc. Exp. Biol. Med. 86: 376-378. Wagner, J. W., and J. de Groot, 1963. Effect of gold thioglucose injections on survival, organ damage and obesity in the rat. Proc. Soc. Exp. Biol. Med. 112: 33-37. Waxier, S. H., and G. Brecher, 1950. Obesity and food requirements in albino mice following administration of gold thioglucose. Am. J. Physiol. 162 : 428-433.
APRIL 29-MAY 1. PACIFIC EGG AND OULTRY ASSOCIATION'S WESTERN POULTRY CONFERENCE, MI SION VALLEY, CALIFORNIA. JULY 25-31, 1971. 25TH INTERNATIONAL CONGRESS OF PHYSIOLOGICAL SCIENCES, MUNICH, GERMANY.
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had extensive damage in the ventromedial area of the hypothalamus following GTG injection. The LD50 of GTG in broiler chicks is much higher than the LD50 of GTG in Japanese quail. Carpenter et al. (1969) observed that the LD50 of GTG in Japanese quail varied from 0.03 to 0.09 mg./g. body weight. In the present experiments, the LD00 of GTG in Peterson-Cross broiler chicks appeared to be close to 0.5 mg./g. body weight. The LD50 of GTG in mice is approximately 1.0 mg./g. body weight (Waxier and Breecher, 1950). None of the animals that had received the control injections died in the present experiments. The importance of genetic factors controlling the susceptibility of animals to GTG was demonstrated by Liebelt and Perry (1957). These workers reported that two genetically independent inbred strains of mice differed with regard to GTG induced hypothalamic damage and obesity. Talbert and Hamilton (1954) did not produce obesity with GTG injections in immature, adult and castrate rats. Wagner and de Groot (1963) showed that GTG affected the ventromedial nuclei in rats, but it was difficult to produce obesity because the obesogenous dose was very close to the lethal dose.
1345
1341
Raghuramula, N., B. S. N. Rao and C. Gopalan, 1965. Amino acid imabalance and tryptophanniacin metabolism I. Effect of excess leucine on the urinary excretion of tryptophan-niacin metabolites in rats. J. Nutr. 86: 100-106. Tannous, R. I., Q. R. Rogers and A. E. Harper, 1966. Effect of leucine-isoleucine antagonism on the amino acid pattern of plasma and tissues of the rat. Arch. Biochem. Biophys. 113: 356361. Zimmerman, R. A., D. C. Snetsinger, D. W. Cardin and D. E. Greene, 1969. Amino acid imbalances in practical poultry diets. Poultry Sci. 48: 1894.
K. L. SIMKINS AND J. M. PENSACK Agricultural Division, American Cyanamid Company, Princeton, N.J. 08540 (Received for publication May 4, 1970) INTRODUCTION
W
AXLER and Brecher (1950) reported that about one-third of the stock albino mice that survived a single LD50 dose of gold thioglucose (GTG) developed varying degrees of hyperphagia and obesity. Marshall et al. (1955) found that the GTG induced obesity in mice was associated with lesions in the ventromedial nuclei in the hypothalamus. Liebelt and Perry (1957) reported that GTG produced different degrees of hypothalamic damage and obesity in two genetically independent inbred strains of mice. At the time the present study was initiated, there were no reports concerning the effect of GTG on fowl. Recently, Carpenter et al. (1969) reported that feed consumption, body weight and reproduction of Japanese quail were not affected by GTG treatment. Carpenter et al. (1969) did not find any evidence of destruction in either the hypothalamus or amygdala in GTG treated quail. The objectives of the present study
were: (1) to determine the approximate LD50 dose of a single intramuscular GTG injection in five day old broiler chicks, (2) to determine the effect of GTG on feed consumption and weight gain by broilers, and (3) to compare the effects of GTG in mice and broilers. MATERIALS AND METHODS
Peterson-Cross broiler chicks (Kerr Chickeries, Frenchtown, N.J.) were housed in wire batteries in a room where the heat was thermostatically controlled. The chicks had access to water and the ration shown in Table 1 at all times. Each chick was weighed and identified prior to injection. Gold thioglucose (Schering Corp., Bloomfield, N.J.) suspended in sesame oil was injected into the leg muscle when the chicks were 5 days old. The quantity of GTG injected was 1.0 and 0.5 mg./g. of body weight in Experiments 1 and 2, respectively. Control chicks were injected with a solution composed of 10% polyethylene glycol, 0.81% sodium chloride,
Downloaded from http://ps.oxfordjournals.org/ at University of North Dakota on May 17, 2015
Effect of Gold Thioglucose on Survival, Feed Consumption and Body Weight of Broilers
1342
K . L . SlMKINS AND J . M . PENSACK TABLE 1.—Composition of Broiler Ration Ingredient
Ground yellow corn Soybean meal (50% protein) Corn gluten meal Menhaden fish meal (60% protein) Stabilized fat Dehydrated alfalfa meal Ground limestone (33% Ca) Dicalcium phosphate Sodium chloride Trace minerals1 Vitamin premix2
53.4 28.0 5.0 5.0 4.0 2.0 0.5 1.2 0.3 0.1 0.5 100.0
1 Provided 60p.p.m. manganese, 20p.p.m. iron, 20 p.p.m. zinc, 2 p.p.m. copper, 12 p.p.m. iodine, and 0.2 p.p.m. cobalt, in ration. 2 Provided 3,300I.U. vitamin A, 1,1001.U. vitamin D3, 2.2 I.U. vitamin E, 500 mg. choline chloride, 500 mg. DL-methionine, 125 mg. ethoxyquin, 27.5 mg. niacin, 8.8 mg. pantothenic acid, 4.4 mg. riboflavin, 1.43 mg. folic acid, 1.1 mg. menadione, 0.011 mg. vitamin B12 per kilogram of feed.
0.45% carboxymethylcellulose and 0.36% Tween 80 in distilled water. In both experiments, 60 chicks (30 males, 30 females) received the control and GTG injections. In Experiment 1, the chicks were kept in groups of 15 until two days postinjection when the chicks that survived the injection of 1 mg. GTG/g. body weight were placed in individual pens. Control birds that had initial body weights similar to those of the surviving GTG injected birds were also placed in individual pens. The chicks were housed in individual pens for 12 weeks and then sacrificed. Body weights and feed consumptions were recorded every other day during the first six weeks and at weekly intervals thereafter. In Experiment 2, the chicks were kept in groups of 15 until four days postinjection when the chicks that survived the injection of 0.5 mg. GTG/g. body weight were placed on either Experiment 2A or 2B. In Experiment 2A, the twelve week performance of group fed GTG injected and control chicks was compared. There were two pens having four male chicks and two pens
RESULTS AND DISCUSSION
The survival of five day old broiler chicks that received a single intramuscular injection of 1.0 mg. GTG/g. of body weight is shown in Table 2. A total of 56 out of 60 chicks died within 48 hours post-injection. One of the four chicks that survived died 33 days later. The twelve week weight gains and feed consumptions by the three chicks that survived did not appear to be
Downloaded from http://ps.oxfordjournals.org/ at University of North Dakota on May 17, 2015
Total
Percent
having four female chicks for both the control and GTG treatments. The biweekly weight gains and feed consumptions by each pen of birds were analyzed for statistical significance using a factorial design as outlined by Steel and Torrie (1960). In addition, individual bird weights were recorded biweekly. In Experiment 2B, 21 GTG injected birds (11 males, 10 females) were individually fed for a six week period. Since cage space was limited, only four control males and females were individually fed. The six week body weights, feed consumptions, and feed efficiencies were analyzed for statistical significance using a t test with unequal replications as outlined by Steel and Torrie (1960). Experiment 3 was conducted with 60 six week old white female mice, CF1, obtained from Carworth Laboratories. The mice were individually housed in an air-conditioned room (22°C.) and received a commercial mouse ration and water ad libitum. GTG was injected into 50 of the mice at a level of 1.0 mg./g. of body weight and 10 mice received the control injection previously described for chicks. Feed consumption and body weight of each mouse were recorded at weekly intervals for a twelve week period. Terminal body weights and feed consumption by control and GTG treated mice were compared using a t test (Steel and Torrie, 1960).
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EFFECT OF GOLD THIOGLUCOSE
TABLE 4.—Analysis of variance of mean body weights and feed consumption by group fed broilers in Experiment 2A
TABLE 2.—Survival of five day old broiler chicks after receiving a single intramuscular injection of gold thioglucose
Body weights
Survivors/Total
Exp. No.
mg. GTG/g. body wt.
Males
Females
1 2
1.0 0.5
3/30 19/30
1/30 18/30
variation
TABLE 3.—Effect of gold thioglucose on mean body weights (g.) and feed consumption (g./bird) by group fed broilers in Experiment 2A Item
Days Postinfection
No. of birds" Body weight
Feed intake
a
Males Control
Females , G T
G T Q
Contro
Degrees of freedom
Mean squares
6 1 1 6 6 1 6 1 27
8,215,029** 1,108,265** 12,479 170,969** 6,622 7 5,928 36,719 11,558
5 1 1 5 5 1 5 1 23
2 ,320,330** 644,033** 4,485 45,269** 7,432 15,768 2,963 72,385** 4,676
** P < . 0 1 .
GTG did not have any effect on feed consumptions or body weights throughout the twelve week feeding period. The mean body weights and feed consumptions by individually fed chicks in Experiment 2B are shown in Table 5. There were no significant differences between the body weights and feed consumptions of the GTG treated and control birds. The injection of 0.5 mg. GTG/g. body weight did not significantly (P > .10) affect the feed conversion (g. feed/g. gain) in Experiments 2A and 2B. In Experiment 3, 18 out of 50 six week old mice that received a single intramuscular injection of 1.0 mg. GTG/g. body weight died. The twelve week body weights and feed consumptions by the mice that survived are presented in Table 6. When all 32 surviving GTG injected mice are compared to the 10 control mice, the difference in body weight gain is significant (P <
G
8
8
8
8
0 14 28 42 56 70 84
75 338 798 1,364 2,048 2,617 3,109
74 300 780 1,345 2,034 2,370 3,232
80 341 719 1,164 1,612 2,068 2,391
74 298 695 1,094 1,613 2,035 2,363
5-14 15-28 29-42 43-56 57-70 71-84
296 867 1,111 1,542 1,778 1,740
275 879 1,148 1,549 1,884 1,934
281 736 958 1,244 1,444 1,499
258 746 926 1,201 1,342 1,587
One G T G treated male and one G T G treated female died during the experiment.
TABLE 5.—Effect of gold thioglucose on mean body weights and feed consumption {g./bird) by individually fed broilers in Experiment 2B Item
Days postinfection
Males Control
Feed intake
Control
GTG
10
No. of birds Body weight
Females
GTG
10
0 14 28 42
73 323 767 1,203
70 275 746 1,211
76 318 709 1,129
73 285 680 1,103
5-14 15-28 29-42
339 961 1,240
295 880 1,245
326 891 1,109
307 809 1,095
Downloaded from http://ps.oxfordjournals.org/ at University of North Dakota on May 17, 2015
significantly different from those of control chicks. However, the small numbers of chicks involved make any conclusions unwarranted. The survival of broiler chicks that received 0.5 mg. GTG/g. body weight is shown in Table 2. A total of 37 out of 60 chicks survived. There were no differences between the sexes with regard to GTG toxicity. The mean body weights and feed consumptions by group fed chicks in Experiment 2 A are presented in Table 3. An analysis of variance of the body weight and feed consumption data obtained in Experiment 2 A is presented in Table 4. The body weights and feed consumptions by the GTG treated chicks were not significantly different (P > .01) from those by control chicks. There were no significant period by treatment interactions which indicates that
Periods (A) Sex (B) Treatments (C) AXB AXC BXC AXBXC Replicates Error
Feed consumption
Mean squares
Degrees ol: freedom
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K . L. SlMKINS AND J . M . PENSACK
TABLE 6.—Effect of gold thioglucose on body weights and feed consumption by mice in Experiment 3
Control
10 32 (10)* (9) (13)
GTG
12-Week weight • range (g-)
Mean 12 week mouse values Gain (g.)
Feed consump. (g.)
24-33
5.2
435
24-58 46-58 38-44 24-35
16.8 27.9 18.6 7.2
472 537 467 427
a Values in parentheses represent arbitrary breakdown of GTG treated mice into obese, intermediate and non-obese groups.
.01). However, the difference between the feed consumed by the 32 GTG injected mice and the 10 control mice is not statistically significant (P > .10). Since Marshall et al. (1955) reported that non-obese mice weighed 25 to 35 g. and obese mice weighed 45 g. or more, the mice injected with GTG in Experiment 3 were separated into obese, intermediate and nonobese groups on the basis of their body weights (Table 6). The results show that 10 out of 32 GTG injected mice would be considered obese. These results confirm the reports by other workers (Breecher and Waxier, 1949; Waxier and Breecher, 1950) that about one-third of the albino mice that survive a single LD 50 dose of GTG develop obesity. The weight gain and feed consumption by the 10 obese mice were significantly (P < .01) greater than those of the 10 control mice. The results of Experiment 3 demonstrated that some mice are markedly affected by GTG injection, whereas other mice do not appear to be different from controls. Because it was possible that some individual chicks may have been affected by the GTG injection, the ranges in body weights of GTG injected chicks were compared to those of control chicks (Table 7). The data in Table 7 indicates that none of
TABLE 7.—Comparison of ranges of body weights (g.) of control and gold thioglucose treated broilers
Exp.
Weeks postinjection
2A
6
Male 1,174-1,474 Female 1,098-1,249
1,154-1,452 1,010-1,233
12
Male 2,704-3,574 Female 1,972-2,647
2,803-3,575 2,224-2,518
6
Male 1,157-1,249 Female 1,003-1,207
1,129-1,280 930-1,245
2B
C
^
j ., K
Control
GTG
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Treatment
No. of
the chicks injected with 0.5 mg. GTG/g. body weight had significantly greater body weights than the control chicks. The percent mortality produced by the injection of 1.0 mg. GTG/g. body weight in mice was very similar to that produced by the injection of 0.5 mg. GTG/g. body weight in chicks (36 and 38%, respectively). Since approximately one-third of the surviving mice developed hyperphagia, it appears that the GTG dosage given to chicks would have been sufficient to produce hyperphagia in a few survivors if GTG had a similar effect on mice and chicks. Since none of the GTG injected chicks exhibited hyperphagia and increased body weight, it was concluded that a single intramuscular injection of 0.5 mg. GTG/g. body weight in five day old Peterson-Cross chicks does not affect weight gain and feed consumption by surviving birds. The results of the chick experiments agree with the results of the Japanese quail experiments reported by Carpenter et al. (1969). These workers found that a single intramuscular GTG injection did not affect the feed consumption, body weight or reproduction by Japanese quail. Carpenter et al. (1969) were unable to find any histological evidence that GTG damages the hypothalamus in Japanese quail. Marshall et al. (1959) showed that hyperphagia and obesity occurred only in those mice that
EFFECT OF GOLD THIOGLUCOSE
SUMMARY
The survival of five day old PetersonCross broiler chicks that received a single intramuscular injection of 0.5 and 1.0 mg. GTG/g. body weight was 62 and 7%, respectively. The body weights and feed con-
sumptions by chicks that survived the injection of 0.5 mg. GTG/g. body weight were not significantly (P < .05) different from those of control chicks at either 6 or 12 weeks postinjection. The survival of six week old white mice injected with 1.0 mg. GTG/g. body weight was 64%. Hyperphagia and obesity were observed in approximately one-third of the survivors. REFERENCES Brecher, G., and S. H. Waxier, 1949. Obesity in albino mice due to single injections of goldthioglucose. Proc. Soc. Exp. Biol. Med. 70: 498-501. Carpenter, J. W., C. M. Stein, A. Silverstein and A. van Tienhoven, 1969. The effect of gold thioglucose on food consumption and reproduction of the Japanese quail {Coturnix Coturmx Japonica). Poultry Sci. 48: 574-578. Liebelt, R. A., and J. H. Perry, 19S7. Hypothalamic lesions associated with gold thioglucose-induced obesity. Proc. Soc. Exp. Biol. Med. 95: 774-777. Marshall, N. B., R. J. Barnett and J. Mayer, 1955. Hypothalamic lesions in gold thioglucose injected mice. Proc. Soc. Exp. Biol. Med. 90: 240-244. Steel, R. G. D., and J. H. Torrie, 1960. Principles and Procedures of Statistics. McGraw-Hill Book Co., Inc., New York, N.Y. Talbert, G. B., and J. B. Hamilton, 1954. Failure to produce obesity in the rat following gold thioglucose injection. Proc. Soc. Exp. Biol. Med. 86: 376-378. Wagner, J. W., and J. de Groot, 1963. Effect of gold thioglucose injections on survival, organ damage and obesity in the rat. Proc. Soc. Exp. Biol. Med. 112: 33-37. Waxier, S. H., and G. Brecher, 1950. Obesity and food requirements in albino mice following administration of gold thioglucose. Am. J. Physiol. 162 : 428-433.
APRIL 29-MAY 1. PACIFIC EGG AND OULTRY ASSOCIATION'S WESTERN POULTRY CONFERENCE, MI SION VALLEY, CALIFORNIA. JULY 25-31, 1971. 25TH INTERNATIONAL CONGRESS OF PHYSIOLOGICAL SCIENCES, MUNICH, GERMANY.
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had extensive damage in the ventromedial area of the hypothalamus following GTG injection. The LD50 of GTG in broiler chicks is much higher than the LD50 of GTG in Japanese quail. Carpenter et al. (1969) observed that the LD50 of GTG in Japanese quail varied from 0.03 to 0.09 mg./g. body weight. In the present experiments, the LD00 of GTG in Peterson-Cross broiler chicks appeared to be close to 0.5 mg./g. body weight. The LD50 of GTG in mice is approximately 1.0 mg./g. body weight (Waxier and Breecher, 1950). None of the animals that had received the control injections died in the present experiments. The importance of genetic factors controlling the susceptibility of animals to GTG was demonstrated by Liebelt and Perry (1957). These workers reported that two genetically independent inbred strains of mice differed with regard to GTG induced hypothalamic damage and obesity. Talbert and Hamilton (1954) did not produce obesity with GTG injections in immature, adult and castrate rats. Wagner and de Groot (1963) showed that GTG affected the ventromedial nuclei in rats, but it was difficult to produce obesity because the obesogenous dose was very close to the lethal dose.
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