The effect of melatonin on cisplatin induced neurotoxicity in rats

Cisplatin (Cis) induced neurotoxicity is thought to be caused by oxidative stress and inflammation. Melatonin (Mel) is a well known antiinflamatory and antioxidative drug. We aimed to assess the effects of Mel on Cis induced neurotoxicity in rats. We divided fourty eight rats into six groups as: Control (0.9% NaCl), Vehicle (5% ethanol), Cis (6 mg/kg), Cis (6 mg/kg) + Vehicle (5% ethanol), Mel (20 mg/kg) and Cis (6 mg/kg) + Mel (20 mg/kg). We used Cis as a single dose and Mel for 5 days. After drug injections, we performed T-maze, rotarod and hot plate tests. Rats were sacrificed after behavioral tests and AChE, oxidative stress markers and proinflammatory cytokines were studied from the dissected brain. Cognitive and motor functions were impaired in Cis and Cis+Vehicle groups. Mel repaired cognitive impairment significantly (p<0.05) and motor function insignificantly. While AChE, TBARS and MAO levels were higher in Cis and Cis+Vehicle groups compared to control group (p<0.05), there was a significant decrease in MAO levels but an insignificant decrease in AChE, TBARS levels in Cis+Mel group. SOD and GPx levels were lower in Cis+Vehicle group compared to the control. They increased with the addition of Mel. While GR activity was low in Cis+ Vehicle group, it was higher in Cis + Mel group. TNF- levels were high in Cis and Cis + Vehicle groups, returned to the control group levels with the addition of Mel. IL-6 and IL-1β levels were high in all 3 Cis groups. There wasn't any change with Mel. These results support that melatonin may be an effective agent in preventing the Cis induced neurotoxicity. However, to reach a definitive conclusion, further studies are required using melatonin in different doses and in different periods.