Coenzyme Q10 Alleviates Cyclophosphamide Testicular Toxicity in Rats Via Activating PPAR-Γ and Nrf2 Signaling, and Down-Regulating NF-Κb And Bax/Bcl-2 Ratio

Abstract

Cancer and autoimmune diseases are both treated with the chemotherapy drug cyclophosphamide (CP). However, because of its harmful side effects, particularly testicular toxicity, its use is restricted. The aim of this experiment was to evaluate the effect of coenzyme q10 (CoQ10) on CP induced testicular toxicity in adult 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 a highly significant decrease in reproductive hormones (Testosterone, FSH and LH), anti-oxidant enzymes (SOD, CAT, GSH) and conversely (MDA) levels were markedly elevated. It activated the inflammatory pathway manifested by elevated serum inflammatory cytokines (TNF-α, IL-1β) and up-regulated testicular NF-kB p65 gene. CP affected PPAR-γ and Nrf2 pathway by down-regulating their gene expression in testicular 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 testicular tissues. However, treatment with CoQ10 ameliorated reproductive hormones, increased anti-oxidant enzymes, up-regulated PPAR-γ and Nrf2 gene expression besides regulated inflammation and apoptosis. Histological improvement of testes also strengthened the defensive effects of CoQ10. These outcomes advocated CoQ10 as a potent natural remedy that reduces the damaging effects of CP on the testes.