Methotrexate-induced Changes in Rat Parotid and Submandibular Gland Function

Abstract

Methotrexate (MTX) was injected intraperitoneally at a dose of 15 mglkg into adult rats daily for three consecutive days. When compared with saline-injected, ad libitum-fed rats or pair-fed saline-injected rats, MTX decreased unstimulated parotid gland weight, RNA content, and amylase content. RNA content was also decreased in submandibular glands. The pqrotid and submandibular gland outputs of sodium and chloride, but not that of potassium, were decreased following MTX injection. Ductal perfusion demonstrated decreased net efflux of sodium and chloride from the excretory duct of the submandibular gland. The effects of MTX on unstimulated parotid gland weight, RNA content, and amylase content are consistent with its ability to inhibit protein synthesis through depletion of folate co-factors. However, the mechanism by which the alterations in ion transport occurred is not clear at this time.

References

Bernfeld, P. (1951): Enzymes of Starch Degradation and Synthesis, Adv Enzymol 12:379-428.

Branski, D. ; Lebenthal, E. ; Freeman, A.I. ,; Fisher, J.E. ; Hatch, T.F. ; and Krasner, J. (1970): Methotrexate (MTX) Effect on Pancreatic Enzymes in Leukemic Mice. Dig Dis Sci 24:865-871.

Burton, K. (1968): Determination of DNA Concentration with Diphenylamine , Methods Enzymol 12(B):163-167.

Courts, F.J. and Mueller, W.A. (1983): Suppression of Salivary IgA Secretion by Methotrexate , J Dent Res 62:181, Abst. No. 102 (AADR).

Drury, H.F. (1948): Identification and Estimation of Pentoses in the Presence of Glucose, Arch Biochem 19:455-466.

El Dareer, S.M. ; Tillery, K.F. ; and Hill, D.L. (1981): Disposition of 5-Methyl-tetrahydrohomofolate and Methotrexate in Rats, Cancer Treat Rep 65:101-106.

Hall, H.D. and Schneyer, C.A. (1964): Salivary Gland Atrophy in Rat Induced by Liquid Diet, Proc Soc Exp Biol Med 117:789-793.

Izutsu, K.T. ; Truelove, E.L. ; Bleyer, W.A. ; Anderson, W.M. ; Schubert, M.M. ; and Rice, J.C. (1981): Whole Saliva Albumin as an Indicator of Stomatitis in Cancer Therapy Patients, Cancer 48:1450-1454.

Johnson, D.A. (1982): Effect of a Liquid Diet on the Protein Composition of Rat Parotid Saliva, J Nutr 112:175-181.

10.

Johnson, D.A. and Sreebny, L.M. (1982): Effect of Increasing the Bulk Content of the Diet on the Rat Parotid Gland and Saliva, J Dent Res 61:691-696.

11.

Lowry, O.H. ; Rosebrough, N.J. ; Farr, A.L. ; and Ran-Dall, R.J. (1951): Protein Measurement with the Folin Phenol Reagent , J Biol Chem 193:265-275.

12.

Loyter, A. and Schramm, M. (1962): The Glycogen-Amylase Complex as a Means of Obtaining Highly Purified Alpha-amylases, Biochem Biophys Acta 65:200-206.

13.

Philips, F.S. ; Thiersch, J.B. ; and Ferguson, F.C. (1950): Studies of the Action of 4-Aminopteroylglutamic Acid and its Congeners in Mammals, Ann NY Acad Sci 52:1349-1359.

14.

Robinovitch, M.R. and Sreebny, L.M. (1969): Separation and Identification of Some of the Protein Components of Rat Parotid Saliva, Arch Oral Biol 14:935-949.

15.

Romaniuk, K. ; Gavin, J.B. ; and Adkins, K.F. (1983): The Effect of Methotrexate on Salivary Glands in the Rat, J Dent Res 62:678, Abst. No. 261 (IADR).

16.

Schneyer, L.H. (1968): Secretory Processes in Perfused Excretory Duct of Rat Submaxillary Gland, Am J Physiol 215:664-670.

17.

Schneyer, C.A. and Hall, H.D. (1976): Neurally Mediated Increase in Mitosis and DNA of Rat Parotid with Increase in Bulk of Diet, Am J Physiol 230:911-915.

18.

Schum, C.A. ; Izutsu, K.T. ; Molbo, D.M. ; Truelove, E.L. ; and Gallucci, B. (1979): Changes in Salivary Buffer Capacity in Patients Undergoing Cancer Chemotherapy, J Oral Med 34 :76-80.

19.

Sreebny, L.M. and Johnson, D.A. (1968): Effect of Food Consistency and Decreased Food Intake on Rat Parotid and Pancreas, Am J Physiol 215:455-460.

20.

Suddick, R.P. and Shannon, LL (1970): Salivary Na, K, and Cl Secretion Rates: Relationship to a Fluid Generation Mechanism, Jpn J Physiol 20:540-549.

21.

Thaysen, J. ; Thorn, H. ; and Schwartz, N.A. (1954): Excretion of Sodium, Potassium, Chloride and Carbon Dioxide in Human Parotid Saliva , Am J Physiol 178:155-159.

22.

Young, J.A. ; Fromter, E. ; Schogel, E. ; and Hamann, K.F. (1967): A Microperfusion Investigation of Sodium Resorption and Potassium Secretion by the Main Excretory Duct of the Rat Submaxillary Gland, Pflügers Arch 295:157-172.