Oxidattve-Hepatic Injury of Isoniazid-Rifampicin in Young Rats Subjected to Protein and Energy Malnutrition

Abstract

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.

Isoniazid induced hepatotoxicity and its amelioration with ethanolic extract of stem bark of Berberis lycium Royale in mice

“…19 Hepatotoxicity due to antitubercular drugs is established to be mediated through free radical damage and oxidative stress to hepatocytes. 20 It is recognized that in sub-acute and chronic inflammation, reactive oxygen species (ROS) play a main role in modulating the inflammatory response and subsequent cell and tissue injury. Antioxidants are documented as probable protective agents in diminishing the oxidative damage of cells from ROS and hamper the progress of many diseases.…”

Spirulina maxima Protects Liver From Isoniazid and Rifampicin Drug Toxicity

“…9 Several studies have shown that rifampicin causes oxidative injury of liver, its membrane, and organelles, leading to lipid peroxidation and depletion of glutathione and the free radical scavenging enzymes. 10 Since long-term use of these drugs causes liver damage, supplementation with hepatoprotective drugs is highly desired to protect from hepatic damage caused by tuberculosis drugs.…”

Hepatoprotective Effect of Calotropis procera in Isoniazid and Rifampicin Induced Hepatotoxicity

“…26,27 The mechanism of hepatotoxicity has been suggested by these two drugs is mediated via oxidative damage, 28 the additive or synergistic hepatotoxic effect has been reported to the caused by monoacetyl hydrazine, hydrazine and other related compounds produced from hepatic biotransformation through enzyme induction; 29 therefore, a regular weekly or biweekly monitoring of liver enzyme is required for initial 2 months, 30 according to the guidelines of American thoracic society a rapid increase in liver enzyme like ALT is one of the most prominent indicator for development of hepatic injury. 31,32 In order to manage the ATT induced hepatotoxicity it is recommended to hold the treatment when the hepatotoxicity is evident, until the liver enzymes normalize.…”