Evaluation of the potential effects of methotrexate and melatonin administration on sciatic nerve regeneration in an experimental rat model of diabetes

Objective: Methotrexate (MTX), a folic acid antagonist used as a chemotherapeutic agent, exhibits neurotoxic effects, while melatonin (MEL), an antioxidant with neuroprotective properties, accelerates nerve healing by reducing oxidative stress. This study investigates the combined effects of MTX and MEL on peripheral nerve regeneration and conduction ability in a streptozotocin (STZ)-induced diabetic rat model. Materials and Methods: A total of 40 male Wistar Albino rats were used in the study. Diabetes was induced by STZ injection. The rats were divided into five groups, sham (n=8), control (n=8), MTX (n=8), MEL (n=8), and MTX plus MEL (n=8) and different treatment protocols were applied and then functional, histopathological and biochemical evaluations were performed. Nerve regeneration was evlauated with electrophysiological examinations, walking tests and biochemical analyses. Results: While MTX administration alone exhibited neurotoxic effects, MEL was observed to support nerve healing due to its antioxidant properties. In combination of MTX and MEL groups, MEL partially mitigated MTX-induced nerve degeneration. Histopathological analyses revealed better preservation of myelin sheath and axonal integrity in the MEL group. Conclusion: It is concluded that MTX negatively affects nerve regenerationexogenous administration of MEL could partially alleviate MTX-induced nerve damage in STZ-diabetic diabetic subjects. Keywords: Diabetic neuropathy, methotrexate, melatonin, nerve regeneration, oxidative stress