Investigating the Effect of Benfotiamine in Paclitaxel-induced Peripheral Neuropathy

Abstract

Background: Chemotherapy-induced peripheral neuropathy (CIPN), particularly due to paclitaxel, remains a dose-limiting adverse effect. Benfotiamine, a lipid-soluble thiamine precursor, has shown anti-inflammatory, antinociceptive, and neuroprotective effects experimentally. Objectives: To investigate the effect of benfotiamine in paclitaxel-induced peripheral neuropathy and elucidate the mechanisms involved. Materials and Methods: CIPN was induced by paclitaxel (2 mg/kg, i.p., four alternate days) in rats. Thermal hyperalgesia and mechanical allodynia were assessed, and TNF-α level was estimated in DRG and spinal cord. Oxido-nitrosative stress was assessed by estimating TBARS and nitrite levels, and SOD activity. Results: Administration of paclitaxel evoked marked thermal hyperalgesia and mechanical allodynia parallel to an increase in neuro-immune activation and oxidative stress. Benfotiamine (100 and 300 mg/kg, p.o.) administration for 2 weeks, started 14 days after paclitaxel injection, significantly alleviated pain hypersensitivity on days 21 and 28. These observed antihyperalgesic and antiallodynic effects of benfotiamine are accompanied by a marked reduction of TNF-α in both DRG and spinal cord, as well as markers of oxido-nitrosative stress in the spinal cord. Conclusion: These findings provide evidence for the antinociceptive potential of benfotiamine, partly by inhibiting neuro-immune activation and in part by reducing oxido-nitrosative stress in paclitaxel-induced neuropathy, and represent a novel therapeutic approach for alleviation of CIPN clinically.