Title:Zinc Gluconate Supplementation Protects against Methotrexate-induced Neurotoxicity in Rats via Downregulation of Oxidative Stress, Inflammation and Neuron-specific Enolase Reactivity in Rats
Volume: 13
Issue: 3
Author(s): Anthony T. Olofinnade, Adejoke Y. Onaolapo, Olufemi B. Okunola and Olakunle J. Onaolapo*
Affiliation:
- Behavioural Neuroscience and Neuropharmacology Unit, Department of Pharmacology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
Keywords:
Methotrexate, chemotherapy, cognitive deficit, neurotoxicity, neuron specific enolase, zinc.
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: 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.
