Demonstration of the protective effect of propofol in rat model of cisplatin-induced neuropathy

Abstract

Cisplatin is commonly used in the treatment of lung, genitourinary, and gastrointestinal cancers. Peripheral neuropathy is the most important side effect, leading to a decrease in the dose of cisplatin or its complete cessation in the early period. 16 rats were given cisplatin at a dose of 2.5 mg/ kg/day twice a week for 4 weeks to induce neuropathy model. The rats taking Cisplatin were divided into 2 groups. Group 1 rats (n = 8) were given 1 ml/kg/day 0.9 % NaCl intraperitoneally, and Group 2 rats were given 10 mg/kg/day Propofol intraperitoneally daily for 4 weeks. The remaining 8 rats served as the control group. At the end of the study, all animals were tested for motor functions. Blood samples were collected for the measurement of plasma lipid peroxidation (malondialdehyde; MDA), tumor necrosis factor (TNF-α), glutathione (GSH), IL-6 and HSP-70 levels. Electromyography fi ndings revealed that compound muscle action potential (CMAP) amplitude was signifi cantly higher in the cisplatin-Propofol group than in the cisplatin-saline group. Also, cisplatin-Propofol treated group showed signifi cantly lower TNF-α, MDA and IL-6 levels and higher GSH and HSP-70 levels than cispalatin-Saline group (p < 0.01, p < 0.001). In addition, while the CMAP latency was decreased in the propofol group, the CMAP amplitude was increased, and a signifi cant improvement was observed in the Inclined test scores. Besides, histological examinations showed an increase in axon diameter and NGF expression with Propofol treatment. This study demonstrated that Propofol exerts protective activity against cisplatin-induced neurotoxicity by increasing endogenous antioxidants and reducing lipid peroxidation and infl ammation (Tab. 3, Fig. 4, Ref. 30).