Colistin sulphate induced neurotoxicity: Studies on cholinergic, monoaminergic, purinergic and oxidative stress biomarkers

Abstract

This study evaluated the influence of colistin sulphate on cholinergic, monoaminergic, purinergic and oxidative stress biomarkers in the brain of male rats. Rats were randomized into four (4) groups (A-D) of five rats each. Group A rats received the vehicle of administration for 7 days. Rats in groups B, C and D received 5-, 7.5- and 15-mg/kg body weight colistin sulphate intravenously for 7 days. Colistin sulphate administration significantly raised the narrow beam, landing foot spread distance and gait scores. Administration of colistin sulphate dose dependently increased the activities of acetylcholinesterase, butyrylcholinesterase, monoamine oxidases A and B, ecto-nucleoside triphosphate diphosphohydrolase and ecto-5′ nucleotidase. Furthermore, the activities of superoxide dismutase, catalase and glutathione S-tranferase activities in the brain of rats treated with colistin sulphate decreased significantly. Similarly, colistin sulphate lowered the level of reduced glutathione. Caspase-3, malondialdehyde and fragmented DNA in the brain of rats were significantly raised. Colistin sulphate induced gross nuclear condensation and depletion, in addition to cytoplasmic degenerative changes and dilated blood vessels in the brain of rats. Available data from this study show that alterations in the cholinergic, monoaminergic, purinergic and oxidative stress biomarkers are associated with colistin sulphate-mediated neurotoxicity.