Cancer and autoimmune diseases are both treated with the chemotherapy drug cyclophosphamide (CP). However, because of its harmful side effects, particularly hepatotoxicity, its use is restricted. The aim of this experiment was to evaluate the effect of coenzyme q10 (CoQ10) on CP induced hepatotoxicity in adult male albino rats. Sixty adult male albino rats (180-200 g) were divided into 6 groups, 3 control groups and 3 experimental groups {CoQ10-treated group, CP-treated group and CP+CoQ10-treated group}. After 4 weeks of treatment, blood samples were collected for biochemical studies, while tissues were taken for oxidative stress markers, qRT-PCR, histopathological and immunohistochemical studies. Our outcomes clarified that CP provoked an increase in liver enzymes (ALT, AST, ALP and γGT) along with severe hepatic histopathological changes. Also, CP showed a subsequent decrease in the antioxidant enzyme activities (SOD, CAT, GSH), and conversely, (MDA) levels were markedly elevated. CP activated the inflammatory pathway demonstrated by elevated serum TNF-α and IL-1β, and up-regulated hepatic NF-kB p65 gene expression. CP affected PPAR-γ and Nrf2 pathway by down-regulating their gene expression in hepatic tissues. It also activated apoptotic pathway by up-regulation of Bax and down regulation of Bcl-2 leading to elevated apoptotic index (Bax/Bcl-2) ratio in hepatic tissues. However, treatment with CoQ10 ameliorated liver enzymes, anti-oxidant enzymes, up-regulated PPAR-γ and Nrf2 gene expression besides regulated inflammation and apoptosis. Histological hepatic improvement also fortified the defensive effects of CoQ10. These outcomes advocated CoQ10 as a potent natural medication that reduces the damaging effects of CP on hepatic tissues.

Cyclophosphamide, Coenzyme Q10, hepatotoxicity, PPAR-γ, Nrf2, NF-κB, Bax/Bcl-2