Protective Role of Coenzyme Q10 Against Isoniazid and Rifampicin-Induced Hepatotoxicity in Rats via Modulation of PPAR-γ, iNOS, and NF-κB

Abstract

Current study was an attempt to unravel the molecular mechanisms underlying the protective role of Coenzyme Q10 (CoQ10) in isoniazid (INH) and rifampicin (RIF)-induced hepatotoxicity. The animals were treated with INH and RIF (50 mg/kg b.w.) for 28 days. The protective role of concomitant administration of CoQ10 (10 mg/kg b.w.) was evaluated and compared with that of silymarin (25 mg/kg b.w.). Blood and liver tissue of the study animals were used for the evaluation of antioxidant, immunological and mitochondrial parameters and the estimation of total ROS. The expression of inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NFκB) and peroxisome proliferator-activated receptor gamma (PPAR-γ) were analysed by real time reverse transcriptase polymerase chain reaction (RT-PCR). INH and RIF caused depletion of plasma antioxidant enzymes, nonenzymatic antioxidants and mitochondrial parameters and also resulted in increased lipid peroxidation and ROS as compared to the normal control rats. The serum levels of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were found to be increased in the INH and RIF treated rats. INH and RIF treated rats showed increased expression of iNOS and NFκB and reduced expression of PPAR-γ. Coenzyme Q10 was able to restore normal expression of iNOS and NFκB while significantly increasing the expression of PPAR-γ. It was found that concomitant administration of CoQ10 was able to restore near normal antioxidant status in INH and RIF treated rats.