The Investigation of Ameliorating Effect of Methylene Blue on Cisplatin-Induced Neurotoxicity in Female Rats

Abstract

Objective: Cisplatin is indispensable in many solid tumors, and peripheral neurotoxicity is an essential dose-limiting side effect. The study aims to investigate the ameliorating effect of methylene blue, which has anti-oxidant properties, in rats with neurotoxicity due to cisplatin treatment. Materials and methods: Twenty-four adult female rats were included in the study and divided into 3 groups. The first group (n=8), the control group, did not receive any treatment. The second (n=8) and the third (n=8) group received 2.5 mg/kg/day of cisplatin and 1 ml/kg/day of 0.9% NaCl (saline) twice a week for 4 weeks. Also, the third group received 20 mg/kg/day of methylene blue every day for 4 weeks. Blood samples were collected from rats for malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor- α (TNF-α), and interleukin-6 (IL-6) levels, and electromyography (EMG) and motor function were evaluated. Results: In non-treated cisplatin injected rats, a significant increase in the lipid peroxidation product MDA and pro-inflammatory cytokines compared to the control group (p<0.001). Electromyography measurements also resulted in a significant decrease in cisplatin injected rats’ compound muscle action potential (CMAP) amplitude and prolongation in CMAP latency compared to the control group (p<0.05). A statistically significant decrease in MDA, TNF-α, and IL-6 levels and a statistically significant increase in GSH levels and CMAP amplitude was observed in the methylene blue-treated group compared to the group injected with cisplatin alone. Conclusions: We concluded that methylene blue has ameliorating effects against cisplatin-induced neurotoxicity (CIN) by enhancing anti-oxidative capacity, energy metabolism and suppressing inflammatory parameters and oxidative stress.