Effect of different doses of carotenoids in isoniazid-rifampicin induced hepatotoxicity in rats.

AIM: Isoniazid (INH) and Rifampicin (RIF) are hepatotoxic drugs. Oxidative stress has been reported as one of the mechanisms of INH+RIF induced hepatotoxicity. METHODS: Intragastric administration of INH and RIF (50 mg/kg body weight/day each) for 28 days in Wistar rats is hepatotoxic, indicated by raised transaminases and histology. Carotenoids have antioxidant properties. Therefore, different doses of carotenoids (2.5, 5, 10 and 20 mg/kg body weight/day) were administered to study the hepatoprotective effect against INH+RIF. RESULTS: The higher doses of carotenoids i.e.10 and 20 mg/kg body weight/day showed partial hepatoprotection indicated by return to normal of liver transaminase level and of liver histology in 33.3% of rats. There was no further protective effect seen by increasing the dose of carotenoids from 10 to 20 mg/kg body weight/day. Lower doses of carotenoids, i.e., 2.5 and 5 mg/kg body weight/day were not effective. CONCLUSION: Thus, a minimum dose with maximum hepatoprotection (10 mg/kg b.wt/ day) was selected as the optimum dose in the present study. The hepatoprotective nature of carotenoids in INH+RIF treated rats may be attributed to their antioxidative property.

Effects of malnutrition on the digestive enzymes of the large bowel of young rhesus monkeys.

The aim of the present study was to investigate the effect of mild-to-moderate protein-energy malnutrition (PEM) and rehabilitation on the digestive enzymes of the large bowel in young rhesus monkeys. The presence of these enzymes has already been reported in the large bowel by many authors. The activities of the digestive enzymes, i.e. lactase, sucrase, maltase, trehalase, glucoamylase, leucine aminopeptidase, alkaline phosphatase and gamma-glutamyl transpeptidase, from different parts of the large bowel were determined in 6 controls, 6 PEM and 6 rehabilitated young rhesus monkeys. These monkeys had been used to study the effect of malnutrition on the small intestine and the results have already been published. There was a significant decrease in the sucrase in the ascending colon (p < 0.05); maltase in all the parts of the large bowel (p < 0.05); and glucoamylase activities (p < 0.05) in the caecum segment of the large bowel in the PEM group. The activity of other enzymes, i.e. lactase, trehalase, alkaline phosphatase, gamma-glutamyl transpeptidase and leucine aminopeptidase, was unaffected in the PEM group. The changes in the enzyme activities recovered on rehabilitation of 21 weeks. The result of this study suggest that even mild-to-moderate malnutrition affects the enzyme activity of the large bowel, which recovers on rehabilitation.

Effect of malnutrition on the digestive enzymes of the upper gastrointestinal tract of young rhesus monkeys.

The present study was planned to observe the effect of protein-energy malnutrition on the gastric and duodenal mucosa. The activities of digestive enzymes (i.e. lactase, sucrase, maltase, trehalase, glucoamylase, leucine aminopeptidase, alkaline phosphatase and gamma-glutamyl transpeptidase) from the gastric (fundus, body and antrum) and duodenal mucosa [i.e. first (D1) and second (D2) part of the duodenum] were determined in 6 control, 6 protein-energy malnourished (PEM) and 6 rehabilitated young rhesus monkeys. There was a significant increase in the activity of the lactase enzyme in the antrum, and D1 and D2 portions of the duodenum of PEM monkeys, while the activity of all other enzymes was significantly increased in the D1 and D2 portions only. The increase in the activity of the above-mentioned enzymes became normal upon rehabilitation. There was no change in the enzyme activities of the gastric mucosa in mild-to-moderate PEM states. This study demonstrates that even mild-to-moderate malnutrition states affect the activity of enzymes in the gastric and duodenal mucosa. Enzyme activity recovers on rehabilitation.