Melatonin Supplementation Alleviates Free Radical Load, NF-?B, Cox-2 and IL-1?-Mediated Inflammatory Responses of the Liver of Cisplatin-treated Golden Hamster Mesocricetus auratus

Cisplatin is a chemotherapeutic drug which frequently induces hepato- and renal toxicities. Cisplatin-induced hepatic damage is an area less investigated compared to renal damage. In the present study we investigated the hepatic damage caused by cisplatin and its possible protection by the hormone melatonin. Adult male golden hamster Mesocricetus auratus (? 2 months of age, and ± 100 g bw) were randomly divided into four groups (n=5)- Group I- control (injected with normal saline), group II- cisplatin (single dose of 15 mg/kg bw, ip), group III- melatonin (100 ug/100 g bw ip for 4 days) and group IV- Mel pretreatment followed by cisplatin at the above-said doses. The animals were euthanized 48 hr after the last dose. Liver was dissected out for analysis (histology, antioxidant profile, NF-?B, IL-1?, Cox-2, Hemeoxygenase-I and Nrf2). Cisplatin treatment induced steatohepatitis-like changes in the liver, elevated TBARS and suppressed antioxidant profiles. Further, the expression of NF-?B, IL-1?, Cox-2, and Hemeoxygenase-I were increased and the expression of Nrf2 was decreased suggesting inflammatory damage to liver. Pre-treatment of melatonin reduced the cisplatin-mediated hepatic pro-oxidant/antioxidant balance and inflammatory responses. Therefore, melatonin pretreatment might be a supportive approach in cancer therapy as it negates some of the damaging effects of cisplatin on liver to an extent without interfering with its chemotherapeutic attributes.