Investigating the Effect of Benfotiamine in Paclitaxel-induced Peripheral Neuropathy
Haritha Pasupulati *
Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visva Vidyalayam (Women’s University), Tirupati, Andhra Pradesh, India and Department of Pharmacy Practice, Bharat School of Pharmacy, Hyderabad, Telangana, India.
Satyanarayana SV Padi
Care College of Pharmacy, Hanamkonda, Kakatiya University, Telangana, India.
Sujatha Dodoala
Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visva Vidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.
Prasad VSRG Koganti
Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visva Vidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.
*Author to whom correspondence should be addressed.
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.
Keywords: Benfotiamine, chemotherapy-induced peripheral neuropathy, neuroinflammation, neuropathic pain, neuro-immune activation, oxidative stress, paclitaxel