The effects of the GLP1 analog liraglutide on allodynia and motor coordination in peripheral neuropathy induced by a chemotherapeutic agent, cisplatin

Peripheral neuropathy is one of the dose-limiting side effects of cisplatin (CIS) and still has no effective treatment. In this study, we aimed to investigate the potential protective effects of liraglutide, a Glucagon-like peptide-1 (GLP-1) analogue against CIS-induced peripheral neuropathy. For this purpose, female Sprague Dawley rats (n = 32) were randomly allocated into 4 groups: control, CIS, CIS + liraglutide (once weekly) and CIS + liraglutide (daily). Neuropathic pain was induced by CIS 3 mg/kg/week for 5 weeks. The potential effects of liraglutide were investigated by behavior tests (von Frey, tail flick and footprint analysis), biochemical analysis and histopathological analyses of sciatic nerves and dorsal root ganglions. In the von Frey and tail flick tests, liraglutide demonstrated anti-neuropathic effects. Liraglutide also ameliorated motor coordination which was impaired by CIS. Liraglutide was shown to have beneficial effects against CIS-induced peripheral neuropathy by parameters demonstrating reduction of histopathological damage (stained by toluidine blue) of the sciatic nerves and dorsal root ganglions, suppression of oxidative stress parameters (SOD, CAT and GPx), and inflammatory load (NO, IL-6 and IL-10). Weekly dosing regimen was more effective than daily administration of liraglutide in this study. As a result, liraglutide seems to be the candidate agent for the effective treatment of CIS-induced peripheral neuropathy.