Melatonin ameliorates oxidative stress and reproductive toxicity induced by cyclophosphamide in male mice

Abstract

<jats:p> The present study evaluated the efficacy of melatonin in cyclophosphamide (CP)-induced testicular injury, lipid peroxidative damage, and antioxidant enzymes status of the mice testis on the basis of biochemical and histological studies. Mice were pretreated with four different doses of melatonin (2.5, 5, 10, and, 20 mg/kg by body weight (b.w.)) via intraperitoneal injection for five consecutive days followed by injection with CP (200 mg/kg b.w.) 1 h after the last injection of melatonin on the 5th day. After 24 h, mice were euthanized, testes were immediately removed, and biochemical and histological studies were conducted. Treatment with melatonin significantly mitigates lipid peroxidation, superoxide dismutase, and catalase activity and the level of reduced glutathione content abnormality induced by CP in mice testis. Histological examination clearly demonstrates that pretreatment of melatonin prevented CP-induced spermatogenesis toxicity and spermatogenic cells reduction in mice testis. The protective effect of melatonin is likely due to the antioxidative properties of the indolamine existed in the chemical structure. Because melatonin is a safe, natural compound, it could be used concomitantly as a supplement to protect people undergoing chemotherapy against reproductive toxicity. </jats:p>

Role of melatonin in mitigating chemotherapy-induced testicular dysfunction in Wistar rats

“…The results are also in consonance with results of Atessahin et al (2006), where melatonin mitigates cisplatininduced testicular toxicity in rats. Pre-treatment with melatonin protected against cyclophosphamide-induced testicular and oxidative damage in rodents (Chabra et al, 2013;Ilbey et al, 2009). The present study also demonstrates a recovery in steroidogenesis, spermatogenesis and architecture in rat testis with melatonin administration, which was demonstrated with significant increase in DSP and 3b-and 17b-HSD activities as compared to the PVB-treated rats.…”

Protective effects ofOriganum vulgareethanol extract against cyclophosphamide-induced liver toxicity in mice

“…Normal tissue injury or damage is the major limitation of CP use, which gives rise to numerous side effects, and CP treatment also results in the production of ROS, which cause peroxidative damage to vital organs (Patel, 1987). In our recent study, CP administration induced testicular toxicity and oxidative stress in the testis of male mice (Chabra et al, 2014).…”

Ameliorative action of farnesol on cyclophosphamide induced toxicity in mice

“…The deleterious effects of CP on testis have previously shown in other studies. In a study, single dose (200 mg/kg b.w, i.p) of CP injected to healthy male mice caused a very significant (P < 0.001) reduction in diverse spermatogonia cells in seminiferous tubules in comparison with control group (1). Several studies have shown testicular toxic effects of CP (26)(27)(28).…”

“…Cyclophosphamide (CP; N, N-bis (2-chloroethyl) tetrahydro-2H-1, 3, 2-oxazaphosphorin-2-amine 2-oxide) ( Figure 1A), is an alkylating agent with antineoplastic and immunosuppressive effects used for the treatment of malignancies including lymphomas, breast cancer, leukemia, multiple myeloma and some diseases such as, rheumatoid arthritis, systemic lupus erythematosus (SLE), and in blood stem cell transplantation in humans and animals (1,2). CP, through bioactivation by hepatic microsomal cytochrome P450, produces two active metabolites: phosphoramide mustard and acrolein (3).…”