Eugenol attenuates concanavalin A-induced hepatitis through modulation of cytokine levels and inhibition of mitochondrial oxidative stress

摘要

Paper description: The hepatoprotective effect of the phytochemical eugenol was examined.Concanavalin A (Con A) was used in Wistar albino rats to produce an experimental model of autoimmune hepatitis which mimics acute liver injury in humans. Eugenol, administered by oral gavage (5 mg/kg/day) for 5 days before and during Con A administration, exerted a hepatoprotective effect through modulation of lipid peroxidation, increased antioxidant enzyme activities, restoration of mitochondrial oxidative stress and cytokine levels (anti-inflammatory and anti-fibrogenic effects), as confirmed by histological findings.Eugenol can be considered as a potential hepatoprotective drug.: Therapeutic management of hepatitis with conventional drugs alone worsens hepatic functioning in the long term because of sustained oxidative stress. Active compounds from several plant sources have been investigated to counteract this. Eugenol, a phytochemical abundant in various plants, is known for its wide range of pharmacological effects. There is a lacuna in the deeper understanding of its hepatoprotective activity at the molecular level. Our present study aimed to determine the effects of eugenol on the changes in antioxidant components, inflammatory cytokines and modulation of mitochondrial oxidative stress in immune-mediated hepatitis. We employed a model that mimics viral hepatitis using concanavalin A (ConA) to induce T-cell-mediated acute hepatitis. Eugenol increased (P<0.01) antioxidant enzyme activities, including reduced glutathione (GSH)-regenerating enzyme, glutathione reductase, and glucose-6-phosphate dehydrogenase. Its antiinflammatory and antifibrogenic effects were evident from the reduction (P<0.01) in interleukin and tumor necrosis factor levels. Eugenol was found to decrease mitochondrial oxidative stress, which was elevated in hepatitis. The hepatoprotective effects of eugenol were confirmed by histological findings. The current investigation shows that eugenol exerts a hepatoprotective effect through the modulation of different pathways which include restoration of mitochondrial oxidative stress. Eugenol could be a promising candidate for human hepatitis management, warranting preclinical studies.