Zinc Gluconate Supplementation Protects against Methotrexate-induced Neurotoxicity in Rats via Downregulation of Oxidative Stress, Inflammation and Neuron-specific Enolase Reactivity in Rats

Abstract

Background: The global increase in the incidence of cancers, as well as neurotoxicity induced by cancer therapy, has necessitated research into agents that are neuroprotective without impeding cancer treatment. Objective: The objective of this study is to investigate the neuroprotective effects of feed-added zinc on methotrexate-induced changes in rats. Methods: Animals were grouped into normal control and methotrexate control, which were fed rodent chow and three groups fed zinc gluconate incorporated into the diet at 25, 50 and 100 mg/kg, respectively. Animals in the first group, in addition to normal diet, received intraperitoneal (i.p.) injections of saline at 2 ml/ kg, while rats in the four other groups were administered methotrexate i.p. at 20 mg/kg/day on the last three days (19-21) of the experiment. On day 22, rats were exposed to the behavioural paradigms, following which they were euthanised and blood was taken for biochemical assays. Sections of the hippocampus were homogenised for the assessment of neurotransmitters or processed for histological and immunohistochemical studies. Results: Dietary zinc supplements at certain concentrations protected against the development of methotrexate-induced alteration in body weight, food intake, memory histomorphology, and neuron- specific enolase reactivity. Conclusion: Conclusion: Dietary zinc supplementation was protective against neurotoxicity induced following methotrexate administration, with possible mechanisms being the down-regulation of oxidative stress, inflammation and neuron-specific enolase reactivity.