Selenium Attenuates Paclitaxel-Induced Peripheral Neuropathy by Suppressing Oxidative Stress, Inflammation, and Apoptosis in Rat Sciatic Nerve.

Abstract

Paclitaxel (PTX) is a potent taxane widely used in the treatment of solid tumors and can cause dose-limiting peripheral neuropathy. This study evaluated the therapeutic potential of selenium in a paclitaxel-induced peripheral neuropathy model. A total of 30 male Sprague-Dawley rats were divided into five groups (n=6): Control, SE1, PTX, PTX+SE0.5, and PTX+SE1. PTX (2mg/kg, i.p., days 1-5) was administered followed by SE (0.5 or 1mg/kg, i.g., days 6-15); sciatic nerve tissues were analyzed on day 16. In addition to molecular and histopathological analyses, behavioral assessments were performed to evaluate mechanical nociception, locomotor activity, and anxiety-like behavior. PTX significantly reduced mechanical pain threshold, impaired locomotor performance, and decreased exploratory behavior. At the molecular level, PTX increased oxidative stress by elevating MDA levels while decreasing SOD and GSH; it also increased TNF-α, IL-1β, and IL-6, and reduced IL-10 levels. Histopathologically, marked axonal degeneration and demyelination, along with reduced myelin fiber area, were observed. SE treatment, particularly at 1mg/kg, restored mechanical pain threshold, improved locomotor parameters, and attenuated anxiety-like behavior. SE also brought oxidative stress markers closer to control levels, suppressed pro-inflammatory cytokines, increased IL-10, reduced histopathological damage, and improved myelin integrity. Immunostaining revealed that SE attenuated PTX-induced increases in BAX, caspase-3, and 8-OHdG, while partially reversing the decrease in Bcl-2. In qPCR analyses, PTX decreased BDNF and increased GFAP expression, which were normalized by SE. SE suppressed the PTX-induced increase in Keap-1 and enhanced Nrf-2 expression. In addition, SE treatment partially restored HO-1 expression, with statistically significant increases observed compared to the PTX group, although levels did not fully return to control values.

Key Findings

• Selenium treatment restored mechanical pain threshold and improved locomotor and anxiety-like behaviors in paclitaxel-induced peripheral neuropathy in rats.
• Selenium reduced oxidative stress markers (MDA), increased antioxidant levels (SOD, GSH), suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and increased anti-inflammatory IL-10.
• Selenium enhanced Nrf-2 expression, suppressed Keap-1, partially restored HO-1 levels, and attenuated apoptosis markers (BAX, caspase-3) while improving myelin integrity and reducing histopathological damage.

Clinical Significance

Citation

Tekin Samet, Aykurt Furkan, Bolat Merveet al.. Selenium Attenuates Paclitaxel-Induced Peripheral Neuropathy by Suppressing Oxidative Stress, Inflammation, and Apoptosis in Rat Sciatic Nerve. Neurotoxicology. 2026-Mar-27.