Tuberc Respir Dis.  1976 Sep;23(3):141-150. 10.4046/trd.1976.23.3.141.

Effect of anti-tuberculous agents on pancreatico-biliary function in rats

• KMID: 2528959
• DOI: http://doi.org/10.4046/trd.1976.23.3.141

Abstract

The first evidence of human tuberculosis had been noted in bones of mummies since the age of neolithic. “ Phthisis" which was the first nomenclature of tuberculosis was introduced into, the history in ancient Greek era. Laennec(I804) described the pathologic process of tuberculosis, and Villemin (1865) had successfully transmitted the disease to the experimental animal. Koch(I882) declared his famous Koch’s postulation and reconfirmed that tuberculosis was an infectious disease. New turning point of chemotherapy against tuberculosis was made after introduction of streptomycin, para-aminosalicylic acid, and isoniazid. Subsequently, various drugs have been developed for clinical use. Rifampicin is the most recent antibiotic developed for tuberculosis. Molitor(1949) reported side reactions induced by streptomycin such as hearing difficulty, tinnitus, vertigo, and etc. Waksman (1958) also reported some side reactions caused by kanamycin, capreomycin, and' viomycin. Isoniazid which is the most potent and least toxic drug, might also cause serious peripheral neuritis, and rarely cause hepatic necrosis which is almost fatal. Ethambut이 is. another less toxic drug, but it might cause retrobulbar optic neuritis. The latest rifampicin has rather bizzare untoward reactions which include digestive disturbances, hepatotoxicity, and thrombocytopenia. So far various toxicites of anti-tuberculous drugs such as in gastrointestinal. hepatic, and nervous systems have been studied, but few studies were attempted for the secretory function of glands, particularly about the pancreas. Sometimes, we notice an overt diabetes while we treat tuberculosis patients with one or more of following drugs such as ethambutol prothionamide and pyrazinamide. Singh(1972) experimented with a sliced pancreas of rat for excretory function through incubation and reported that streptomycin increased amylase secretion and decreased tissue content. Choi (1972) studied an in vivo pancreaticobiliary function with several anti-cancer drugs such as bleomycin, 5-FU, ICRF-159, and methotrexate, and reported that amylase secretion was remarkably increased in methotrexate treated group. So far, there is no definite study of pancreaticobiliary function on influence of various antituberculous drugs, and this study is particularly designed for this purpose. Method and Materials: 1. Experimental animal: Albino rats with body weight ranging from 150 to 250 grams were used. Pancreaticobiliary juice was collected for 2 hours after cannulation. 2. Experimental group: a. Experiment 1: Single massive dose of anti-tuberculous drugs (I. P.) administered. 1) Control group, saline. 2) Streptomycin, 100mg/kg. 3) Isoniazid, l00mg/kg. 4) Ethambutol, " 200mg/kg. 5) Cycloserine, 200mg/kg. 6) Viomycin, 100mg/kg. 7) Pyrazinamide, 600mg/kg. 8) Rifampicin, 200mg/kg. (in DMSO solution and oral) b. Experiment 2 : Repeated administration (I. P.) of anti-tuberculous drugs were used in this series of experiments. 1) Rifampicin, 10rrig/kg, p. o., twice a week 2) Streptomycin, 15mg/ kg, i. p. twice a week 3) Ethambutol, 25mg/kg, i. p. , twice a week Similar experiment were conducted both first and fourth weeks respectively, and liver and pancreas were taken out for pathologic examination. c. Determination of enzymes: Bilirubin and cholate values were checked by method modified by Irvin et al (1944) and Magee et al (1952). Amylase determination was made by Sumner’s method (1 924). Lipase determination was made by Cherry and Crandall’s method (1932).
Results
The effect of anti-tuberculous drugs on the pancreatico-biIiary function were studied using albino rats. The drugs were administered in two ways: single toxic dose and repeated therapeutic doses. The followings are summary of results obtained from the experiment: 1. Pancreatico-biliary secretioh was rematkably inhibited in viomycin and rifampicin treated groups, and significant inhibition was observed in streptomycin, isoniazid, cycloserine treated groups. Ethambutol, kanamycin , and pyrazinamide treated groups showed no significant changes to compare with the control group. 2. Bilirubin concentration was significantly increased in ethambutol. kanamycin, and cycloserine treated groups, however, it was somewhat decreased in streptomycin group. 3. Amylase secretion was remarkably decreased both in viomycin and rifampicin treated groups, and it was significantly decreased in streptomycin treated group. 4. Lipase secretion was remarkably decreased both in streptomycin and rifampicin treated groups, but it was significantly increased in cycloserine, kanamycin, and pyrazinamide treated groups. 5. Cholate secretion was decreased in ethambutol treated group, but it was rather increased in viomycin treated group. 6. In repeated therapeutic doses, pancreatico-biliary secretion was remarkably decreased in one' week in ethambutol treated group. But rifampicin treated group showed slight decrease both in one week and four weeks after treatment. There were little changes in bilirubin. 7. In repeated therapeutic doses, amylase secretion was remarkably decreased in ethambutol treated group for one week, and slightly decreased in rifampicin treated group for four weeks. Lipase sercetion was remarkably decreased in ethambutol treated group for one week. 8. Pathological examination of excised liver showed some degree of fatty degeneration in streptomycin treated groups for one and four weeks and in ethambutol treated group for one week.