Chlorogenic acid co-administration alleviates cisplatin-induced peripheral neuropathy in rats

Abstract

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is still an unresolved problem in cisplatin (CIS) use. Objectives: This study investigates possible anti-neuropathic effect of chlorogenic acid (CGA) against CIS-induced CIPN in rats while also investigating the contribution of nitric oxide (NO) to this phenomenon. Methods: Initially, CGA (250–1000 μM) was tested by MTT assay on primary DRG neurons. Subsequently, CIPN was induced in Sprague–Dawley rats by 3 mg/kg intraperitoneal injections of CIS once/week for 5 weeks. CGA (100 mg/kg) was co-administered with CIS, both alone and in combination with l-arginine (LARG) or l-nitro-arginine-methyl-ester (LNAME), to elucidate the contribution of nitrergic system to anti-neuropathic effects. Mechanical allodynia, thermal hyperalgesia, and cold plate tests were performed to test CIPN. Rotarod, footprint analysis, and activitymeter were used to evaluate motor coordination and performance. Tumor necrosis factor alpha (TNF-α) was measured as a marker of inflammation. Histological evaluations of DRG and sciatic nerves (SNs) were performed utilizing toluidine blue staining. Two-way analysis of variance and Kruskal–Wallis following Tukey's test were used as statistical analysis. Results: Higher concentration of CGA (1000 μM) exhibited protective effect against in vitro neurotoxicity. Neither LARG nor LNAME exerted significant change in this effect. Co-administration of CGA alleviated histological abnormalities and neuropathic effects induced by CIS. Ameliorative effect of CGA was not changed in mechanical allodynia but attenuated in cold allodynia, and motor activity/coordination tests by LARG and LNAME. Neuropathic effects of CIS remained unchanged with LARG and LNAME in behavioral experiments. Conclusion: The study identified CGA as candidate agent in mitigating CIPN. NO seems to play a modulatory role in this effect. © 2024 Elsevier B.V., All rights reserved.