Isoniazid impairs memory function in male Swiss mice by elevating pro-inflammatory cytokines and disruption of hippocampal, and prefrontal cortex neuronal morphology.

Isoniazid (INH), a first-line antibiotic for tuberculosis treatment, is known for its efficacy but also for its potential to cause neurotoxic side effects, which include peripheral neuropathy, seizures, and in rare cases, psychosis. This study aimed to evaluate the neurotoxic effects of INH on memory function and its underlying mechanisms in male Swiss mice. Eighteen male Swiss mice (n = 6 per group) were treated orally with INH at doses of 5, 10, and 20 mg/kg for 28 days. The behavioral tests for memory using Y-maze and Morris water maze were conducted afterwards. The brain tissues of the animals were processed for determination of oxidative stress/antioxidant markers, pro-inflammatory cytokines, and neurotransmitter enzymes (acetylcholinesterase and glutamate decarboxylase).The histomorphology of the hippocampus and prefrontal cortex regions of the brains of the animals was done using the Hematoxylin and Eosin staining techniques. The results of the study showed that INH produced a reduction in memory function, with significant impairments at higher doses in the Morris water maze test. Biochemical analyses revealed increased lipid peroxidative product, reduced antioxidant defenses, and elevated pro-inflammatory cytokines in the hippocampus and prefrontal cortex of mice treated with INH. It also produced neurotransmitter enzymes dysregulations of the discrete brain regions of mice treated with INH. The histomorphorological studies revealed that INH produced structural changes in the hippocampus and prefrontal cortex and marked loss of viable neuronal cells. The results obtained from these studies suggest that INH treatment causes memory impairment. These findings highlight the need for strategies to minimize cognitive side effects in patients with tuberculosis on INH therapy.