Preliminary study of astragaloside IV on oxaliplatin-induced peripheral neurotoxicity in rats

Abstract

Objective: As an effective component of Astragalus membranaceus, astragaloside IV (AS-IV) has a history of thousands of years in China. Many evidences have indicated that AS-IV has a potential neuroprotective effect. In this study, we aimed to preliminarily study the effects of AS-IV on oxaliplatin-induced peripheral neurotoxicity (OIPN) in rats. Methods: Intraperitoneal injection of oxaliplatin for 4 weeks (4 mg/kg, twice a week) was used to establish peripheral neurotoxicity in rats. 40 Sprague Dawley rats were randomly divided into five groups, eight rats in each group, including control group, model group, and three AS-IV treated groups. Different doses of AS-IV (5 mg/kg, 10 mg/kg, and 20 mg/kg, daily) were orally administrated to OIPN rats once a day for 4 weeks at beginning of oxaliplatin administration. Behaviors and histologic evaluation of sciatic nerve and dorsal root ganglia (DRG) were performed to assess the changes of peripheral neurotoxicity through mechanical allodynia and cold allodynia, immunofluorescence, H&E staining, myelin staining, and Nissl staining. Results: AS-IV treatments were able to significantly reduce oxaliplatin induced mechanical and cold allodynia. Moreover, AS-IV administration could increase the levels of NGF, but decrease the levels of TNF-α and IL-6 in oxaliplatin induced rats. AS-IV suppressed the activation of Iba-1 in anterior horn of spinal cord of OIPN rats. The myelin sheath degenerations in the sciatic nerve of OIPN rats were repaired after AS-IV administration. Through observation of sciatic nerves and DRG, AS-IV treatments improved the oxaliplatin induced pathologic injuries in a dose-dependent. Conclusion: AS-IV administration was able to attenuate the oxaliplatin-induced peripheral neurotoxicity in rats.