Effect of GM1 on paclitaxel-induced neuropathy in rats

Abstract

Paclitaxel (Taxol) is an anti-cancer drug effective against a wide range of solid tumors. It is known to be neurotoxic in humans. Several studies have demonstrated paclitaxel-induced neurodegeneration and sensory loss in animal models. The mechanisms underlying this dose-limiting side effect are currently unknown and there is no evidence to show the effectiveness of any drugs that can prevent or control these severe side effects. This study reports the use of a rat model of toxic neuropathy to evaluate the role of GM1 as a possible neuroprotectant for paclitaxel. Forty male Wistar rats were equally divided into 4 groups. The C group did not receive any injection. The V and P groups were given a weekly intraperitoneal injection of vehicle (Cremorphor+ethanol) and 16 mg/kg paclitaxel, respectively. The PG group received 30 mg/kg/day GM1 intraperitoneally) with paclitaxel in the same dose as the P group, for 5 consecutive weeks. Quantitative sensory test, nerve conduction velocity (NCV), morphological and morphometrical studies were performed. Prolonged withdrawal time of tail flick and hot plate analgesic tests including reduced tail NCV were observed in the P and V groups. Light-microscopic inspection of the sciatic nerve in the P, PG and V groups showed minimal degenerative axonal changes. The dorsal root ganglia neurons were unaffected in all groups. The morphometric examination presented a significant increase in the percentage of myelinated fibres with a diameter between 8 to 9 [micrometre] in the P, V, and PG groups when compared to the C group. There were no significant differences between the groups in other parameters. At the electron microsopic examination, axons of the sciatic nerve in the P and PG groups revealed microtubule accumulation and the tendency to surround mitochondria, while there was no such evidence in the other groups. Furthermore, abnormality in axonal mitochondria and activated activated Schwann cells with nucleolus like structure were found in the P group. This was also found in the PG and V groups but with less frequency. The results of this study demonstrated that GM1 had some protective role on sensory modality and NCV tests, nad nerve pathological changes in paclitaxel-induced neuropathy.