The protective effects of hesperidin against paclitaxel-induced peripheral neuropathy in rats

Paclitaxel (PTX), which is widely used in the treatment of solid tumors, leads to dose limitation because it causes peripheral neuropathy. This study was conducted to evaluate the potential effects of hesperidin (HES), which has various biological and pharmacological properties, against PTX-induced sciatic nerve damage. For this purpose, Sprague Dawley rats were given PTX 2 mg/kg/b.w for 5 days, then 100 or 200 mg/kg/b.w HES for 10 days, and behavioral tests were conducted at the end of the experiment. The data obtained show that PTX-induced MDA, NF-κB, IL-1β, TNF-α, COX-2, nNOS, JAK2, STAT3, and GFAP levels decreased with HES administration. Moreover, it was observed that SOD, CAT, and GPx activities inhibited by PTX increased with HES administration. It was determined that PTX caused apoptosis in the sciatic nerve by increasing Caspase-3 and Bax levels and suppressing Bcl-2 levels. HES, on the other hand, showed an anti-apoptotic effect, increasing Bcl-2 levels and decreasing Caspase-3 and Bax levels. Also, it was observed that PTX could cause endoplasmic reticulum stress (ERS) by increasing PERK, IRE1, ATF-6, GRP78 and CHOP mRNA transcript levels, while HES could alleviate ERS by suppressing them. The results indicate that neuropathic pain associated with PTX-induced peripheral neuropathy can be alleviated by HES administration and that it is a promising compound for cancer patients. In addition, it is thought that the results of the present study contain information that will shed light for researchers regarding further studies to be conducted with HES.