The effect of a diuretic and antidiuretic on tooth eruption Paul Eric Litvitt, B.S., D.D.S., awl Thostaas J. De Marco, B.S., D.M.D., Ph.D.,* Clevelarzd, Ohio CASE
\VEYTERS
RESERVE
ITSIVERSITY
SCHOOL
OF
DENTISTRY
The eflect of a diuretic and antidiuretic on the tooth eruption rate of female albino rabbits was evaluated. The eruption rate was evaluated by measuring from a reference mark on the tooth to the interdental papilla after a 4-day growth period. Statistical analysis of the difference between experimental and control eruption measurements sho~cd a significant inrrcasr in the eruption rate (p < 0.01) with administration of the antidiuretic. Administration of the diuretic, however, produced no significant effect on the eruption rate. Interstitial fluid pressure may be related to the process of tooth eruption. It seems to be logical to assume that there may be more than one mechanism involved in tooth eruption, but that interstitial fluid pressure is possibly one such mechanism.
T
110 eruption of teeth is one of the more extensively studied but least understootl areas in dentistry. Although eruptive time sequences in human beings and laboratory animals are a relatively simple matter to observe and record, the actual mechanism of eruption is still not fully understood. Massler and &hour8 have defined eruption as “the process whereby the forming tooth migrates from its intraosseous location in the jaw to its functional position within the oral cavity.” Eruption involves not only the tooth coming into occlusal contact, but also the process of continued eruption after occlusal contact is reached. This would include such phenomena as mesial drift or supraeruption in man and the continuous eruption of the incisors in rodents. Incisors of the rabbit and rat, because of their continuous eruption, have been the teeth most commonly studied in research on eruption. Many theories have been proposed to explain the process of tooth eruption, and most of these are concerned with histologic changes that occur during tooth development and the eruptive process. Submitted by Dr. Litvin in partial fulfillment of Science in Dentistry. *Associate Professor of Periodontics and Periodontics.
294
of the requirements Pharmacology;
for Chairman,
the degree
of Mastei
Department
of
Volume Number
35 2
Diuretic
and antidiuretic:
Efect
on tooth eruption
295
The major theories of eruption and their proponents are as follows: (1) Elongation of root and/or growth of pulp (Siche?). (2) Tension on the tooth from the maturing periodontal ligament (Thomas13-15). (3) Control by the vasculature (Constant’ ; Massler and Schour*; Bryerz). (4) Control by the nervous system (King6 ; Taylor and Butcherlz; Millerg). (5) Hormonal control (Baumel) . (6) Growth of follicular sac and/or periodontal ligament ( Gowgie15 ; O’BrienlO ; Main and Adams?). This study was undertaken to examine the theory that interstitial fluid pressure plays a part in tooth eruption. By altering the amount of interstitial fluid in the rabbit and observing the eruption rate, any effect of fluid pressure on the eruption rate should be discernible. MATERIALS
AND
METHODS
The experimental population consisted of eighteen female, white New Zealand rabbits weighing approximately 10 to 12 pounds each. The animals were maintained on a standard laboratory diet (Purina Lab Rabbit Chow). Four rabbits were used during the initial phase of the experiment to determine effective dosages of the diuretic and antidiuretic. Measurements of water intake and urine output were made for 7 days prior to drug administration. In order to alter body fluid, a potent diuretic and antidiuretic agent were employed. Lasix” (furosemide) is a diuretic which acts on the proximal and distal tubules of the kidney and also on the loop of Henle. Pitressint (vasopressin) is the pressor and antidiuretic principle of the posterior pituitary gland. Its action is to increase reabsorption of water by the renal tubules. These two drugs were administered by intramuscular injection in the hind leg in varying doses over a period of 3 days. It was found that 10 mg. (1 c.c.) of Lasix and 20 pressor units (1 cc.) of Pitressin administered twice daily (9 :00 A.M. and 6 :00 P.M) produced a substantial change in body fluid. Therefore, these dose levels were chosen for the experiment. Fourteen rabbits were used in the second phase to examine the effects of these drugs on the eruption rate. To render the animals in a physically acceptable condition for the experimental procedures, 1.0 to 1.2 cc. of the veterinary tranquilizer Acepromazinet was administered by intramuscular injection. In addition, 0.5 to 1.0 cc. of Diabutal (sodium pentobarbital) was injected intramuscularly. Maximum sedative effect was obtained in 30 to 45 minutes. Two initial growth measurements without the experimental drugs were made on all fourteen rabbits. A 4-day growth period was used. During the procedure, the animals were restrained in a small rectangular rabbit box. The right mandibular incisor was cut off about 1 mm. above the crest of the interdental papilla. With the use of a large diamond disk held in a Moto-Tool,§ the right maxillary incisors were cut off at the gingival margin. This included the small palatal incisor with which the lower incisor occludes, in addition to the *Hoechst Pharmaceutical tParke, Davis, Detroit, SAyerst Laboratories, $Diamond Laboratories,
Co., Sommerville, N. J. Mich. Inc., New York, N. Y. Des Moines, Iowa.
296
Lit~vin
cr)ld DC ~fwco
Oral
Burg.
February, 1973
111or~ ~)romillcnt maxill;l~~ incisor. This allowt~tl a true unimpeded eruption rate to tw n~r:~sn~v(l. ,I thin notch n-as made on the vut lower incisor at the crest of the int(‘r(l(‘lltill ~)iII)illa with ;I small, sllarp diamond wheel. All the cuttings were (Lolit under water irrigation from a syringe. Aftc>r the growth period, the distance from the reference notch to the tip of the> illtcrtlental I)apilla was mcasurcd with a fine-pointed adjustable calipers. ‘l’hc tlistanct, \vas rccortlctl by punc.hing holes with the calipers in a piece of 1)il1’(“’ ;111(1subscqucntl,v measuring with a vernier calipers. When the measurcnlt’llts W~IY l)csing mutlc, the papilla \vas pulled down to its base of attachment in ortlcr to provide a stable rcfcrcnec point. Two measurements were made each t im(‘, ant1 the a\cragc OS the two was used for the statistical analysis. After* tllcx two initial growth periods, two more growth measurements were n~atlc \vitll thca IW of the experimental drugs in the previously determined tlosngcs. Scvcn animals were given the diuretic, and seven were given the antitliurc%iv. I)rug administration was begun on the day after the experimental l)rocAedurc in order to prevent any drug interaction with the sedative and anesthetic agents usctl. In order to analyze the data, the difference between the mean control and the m(~?n c~sI)c~rimcutaI measurements was computed for each animal in both drug groups. To tlrterminc anv drug effect, a separate one-tailed t test for related samplcs:~ was performed on the mean difference for each group. RESULTS
All the animals given Pitrcssin showed an increased eruption rate. Table I shows the avcragc control and experimental eruption rates for these rabbits. I
-sis of the mean difference demonstrated a highly significant increase in eruption 0.01). Table II shows the average control and experimental eruption rates and tlifferenc~c~sfor the animals given Idasix. Again, all values arc the means of two scl)aratcl rcladings taken at l-day intervals. There was no definitive directional c*hange in the eruption rate, as was evident in the animals given Pitressin. Statistical analysis revealed that the mean difference was not significant. MtP
(p
<
DISCUSSION
The initial cxperimcnts in which urine output and water intake were mcasurc~tl showed that a true drug effect on the amount of body fluid was produced by both Pitressin and Lasix. The average normal eruption rate of the rabbits used in the study was 1.81 + OX1 mm. for a 4-day interval. Any changes which mere to be elicited in tllc eruption rate, although they might be subtle, should be consistent to show a t11.ug effecat. As shown in this study, the antidiuretic (Pitressin) produced a statistically significant increase (p < 0.01) in the eruption rate, increasing it by a11 average of 0.37 mm. per 4-day interval. Since Pitressin possessesa vasoconstri&\-e Itotential, as well as an antidiuretic potential, one might attempt to
Volume Number Table
Diuretic
35 2
I. Eruption
Babbit
No.
1
measurements
and antidiuretic:
1.54 1.63
3 4
1.59
:
2.02 2.00 1.60
7
1.61
All measurements are in millimeters. average of two consecutive growth periods *Significant at p < 0.01 level. Table
297
Experimental
Difference*
1.68 1.88 2.08 2.47 1.80 2.25
0.14 0.25 0.49
0.45 0.25 0.20 0.78
2.39 Control of 4 days
and each.
experimental
measurements
are
an
are
an
II. Eruption measurements for animals given Lasix
Rabbit
Experintental
Difference
i
No.
2.25 1.87
2.06 2.24
-0.01 0.19
10 11
2.26
2.23
-0.03 0.39
::
14 All average
on tooth eruption
for animals given Pitressin
CO’&tTOl
i
Efect
1
Control
2.22
1.83
2.27 1.70 1.15
measurements are in millimeters. of two consecutive growth periods
0.12 -0.14 0.52
2.39
1.56 1.67 Control of 4 days
and each.
experimental
measurements
relate its effect on tooth eruption to the former property. However, changes in vascular pressure have been shown not to affect tooth eruption to any significant degree.7 In the present study, since cannulation procedures were not carried out to measure the pressure at the fundic area of the teeth, we may only conclude that the drug itself changed the eruption rate. However, it would seem to be most logical to attribute this change to the effect of the drug on interstitial fluid pressure. No definite effect on tooth eruption could be demonstrated by the administration of the diuretic (Lasix) . Unlike the unidirectional change associated with the administration of Pitressin, both increased and decreased eruption rates were observed. Since the net fluid loss in these animals was less than the net fluid gain in the animals that were given Pitressin, the effect of the diuretic on tooth eruption would not be so pronounced as that of the antidiuretic. Whether interstitial fluid pressure is the only eruptive factor has not been shown by this study. In fact, it is highly unlikely that there is a single eruptive mechanism. Also uncertain is whether interstitial fluid pressure plays an eruptive role in the normal state of fluid balance or only in a state of drug-induced fluid increase. Further research on the mechanism of tooth eruption should concern itself with a more thorough assessmentof the role of tissue pressures. Procedures which are capable of accurately measuring slight changes in fluid pressure in the soft tissue surrounding the tooth should be employed. This will most likely involve some method other than direct cannulation because of the questionable results obtained with that method. A mechanical means of changing interstitial fluid pressure, as opposed to drug-produced changes, might also be evaluated.
Oral February,
Surg. 1973
SUMMARY
Fonrtcclt albino t’cmale rabbits were usecl to tleterminc the effect of a diuretic ant1 an antidiuretic (lrug on eruption rate. Control eruption rates were initially nlcasurcd in all animals before any drug was administered. This was done by measuring from a reference mark on the tooth to the interdental papilla after a 4-day growth period. PtZeasurcmentswere again made after the drugs had been c:ircn twice a da\I during the experimental growth period. Statistical analysis of the differences between experimental control eruption ~nc’as~~wn~e~lts showed a significant increase in eruption rate (p < 0.01) with ;Idmillistration of the antidinretic. Administration of the diuretic, however, pi~~tln~tl ii0 significant effect. Interstitial fluid pressure may be related to the process of tooth eruption. It seems to be logical to assume that there may be more than one mechanism in\-olvcd in tooth eruption, but that interstitial pressure is possibly one such mechanism. Further research concerned with changing and accurately measuring various types of tissue pre$sures and their effects on eruption rate is suggested. REFERENCES
Control of Tooth Eruption, J. Dent. L. J., Becks, H., and Evans, H. M.: Hormonal Res. 33: 80-114, 1954. Brger, L. W.: An Experimental Evaluation of the Physiology of Tooth Eruption, Int. Dent. J. 7: 435-478, 1957. Chilton, N. W.: Design and Analysis in Dental and Oral Research, Philadelphia, 1967, J. B. Lippincott Co. Constant, T. E.: The Eruption of the Teeth, Dent. Cosmos 42: 1281-1388, 1900. Gowgiel, J. M. : Eruption of Irradiation-Produced Rootless Teeth in Monkeys, J. Dent. Res. 40: 538-547, 1961. King, J. D.: Dietary Deficiency, Nerve Lesions, and the Dental Tissues, J. Physiol. 88: 62-76. 1936. Main: J.-E.; and Adams, D. : Experiments on the Rat Incisor Into the Cellular Proliferation and Blood Pressure Theories of Tooth Eruotion. Arch. Oral Biol. 11: 163-177. 1966. Massler, M., and Schour, I.: Studies in Tooth development: Theories of Eruption, AM. J.
1. Baume, 2. <3 4. 5. 6. 7. 8.
ORTHOD. 9. Miller,
27:
552-576,
1941.
B.
G.: Investigations of the Influence of Vascularity and Innervation on Resorption and Eruption, J. Dent. Res. 36: 669.ti76, 1957. 10. O’Brien, Mechanism and Movement C., Bhaskar, S. N., and Brodie, A. cf.: Eruptive First Molar of the Rat. J. Dent. Res. 37: 467-484. 195#8. 11. Sicher, H. : Tooth Eruption : The Axial Movemeit of Continuously Growing Teeth, J. Res. 21: 201-210, 1942. 12. Taylor, A. C., and Butcher, E. 0.: The Regulation of Eruption Rate in the Incisor of the White Rat, J. Exper. 2001. 117: 165-188, 1951. 13. Thomas, N. R.: The Role of Collagen Maturation in Alveolar Bone Growth and Eruption, J. Dent. Res. 43: 947, 1964. 14. Thomas, N. R.: The Effects of Inhibition of Collagen Maturation on Eruption in J. Dent. Res. 44: 1159, 1965. 15. Thomas, N. R.: The Properties of Collagen in the Periodontium of an Erupting in The Mechanisms of Tooth Support, A Symposium, pp. 102-106, Bristol, 1967, Wright and Sons, Ltd. Reprint requests to : Dr. Thomas J. De Marco Department of Periodontics School of Dentistry Case Western Reserve University 2123 Abington Rd. Cleveland, Ohio 44106
Tooth in thr Dent. Teeth Tooth Rats, Tooth, John