rifampin and Protein-Energy-Malnutrition

The role of protein and energy malnutrition in the pathogenesis of isoniazid (INH)-rifampicin (RMP) induced hepatic injury was investigated. Status of oxidative/antioxidative profile was the mechanistic approach to enumerate the nature of injury. Weanling rats were fed with ad-libitum quantity of isocaloric diets containing 5% casein based proteins for the production protein and energy malnutrition. INH and RMP (50 mg/kg of each) were injected intraperitonially for a period of two weeks. Analysis of serum transaminases and histopathological observations revealed hepatic injury. Hepatic thiols and blood glutathione were decreased significantly in INH and RMP treated groups. Among antioxidative enzymes, hepatic superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferases (against CDNB and DCNB substrates) showed significant decline of activities in INH and RMP treated groups. The activities of hepatic glutathione reductase, glutathione-S-transferase (against EA substrate) and lipid peroxidation observed significant elevation. A careful comparison of protein and energy restriction revealed a greater degree of oxidative-stress of INH-RMP in protein-restriction.

Topics: Animals; Antioxidants; Antitubercular Agents; Glutathione; Glutathione Transferase; Isoniazid; Lipid Peroxidation; Liver; Male; Protein-Energy Malnutrition; Rats; Rats, Wistar; Rifampin

1. Rifampicin (RMP) induced hepatic injury was investigated in growing rats. The interaction of moderate and severe protein-energy malnutrition (PEM) was also investigated. 2. Status of oxidative/antioxidative profile was studied by the mechanistic approach, to enumerate the nature of injury. 3. Successful hepatic injury in rats was produced by giving intraperitoneal injection of RMP (50 mg/kg/day). 4. Hepatic lipid peroxidation was significantly increased in all the RMP treated rats. 5. Superoxide dismutase, catalase and glutathione peroxidase activities in the hepatic tissue decreased with RMP treatment. 6. Hepatic thiols represented as total and protein-bound thiols, showed significant elevation, whereas the non protein thiols remain unchanged with RMP treatment. 7. Glutathione-S-transferases also showed significant elevation against 1,2-dichloro-4 nitrobenzene (DCNB) and ethacrynic acid (EA) as substrates. 8. The oxidative/antioxidative profile was observed to be more severely affected with coexistence of malnutrition. 9. Histopathological correlation showed an additional fatty infiltration of hepatocytes with coexistence of malnutrition. 10. Thus, in conclusion, it can be speculated that an altered oxidative/antioxidative profile is the closely associated with production of RMP induced hepatic injury.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Bilirubin; Catalase; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Lipid Peroxidation; Liver; Male; Oxidative Stress; Protein-Energy Malnutrition; Rats; Rats, Wistar; Rifampin; Serum Albumin; Superoxide Dismutase