Montelukast Ameliorates Antimony-Induced Neurotoxicity Accompanied by Alterations in Oxidative Stress,...

Antimony (Sb) is a metalloid widely used in industry, especially in the manufacture of polyethylene terephthalate (PET), commonly used to make water bottles, food packaging, and other consumer products. Recently, Sb has been identified as a novel nerve toxin, which elicits neuronal death and associated neurodegeneration. Montelukast, a cysteinyl leukotriene receptor antagonist, has demonstrated neuroprotective effects in various experimental models of neurodegenerative disorders. This study was designed to explore the neuroprotective effect of montelukast against Sb-induced neurotoxicity. Thirty Swiss albino mice were randomly allocated into five different groups: control, montelukast (M) per se, Sb-10 mg/kg, Sb + M1 (Sb 10 mg/kg + montelukast 5 mg/kg), and Sb + M2 (Sb 10 mg/kg + montelukast 10 mg/kg) groups. Spatial memory, oxidative stress (lipid peroxides, reduced glutathione), cholinergic function (acetylcholinesterase), neuroinflammatory parameters (myeloperoxidase, tumour necrosis factor-α, interleukins-6 and 10), mitochondrial enzyme activities (I, II, IV), neurotrophin (BDNF and CREB), and histopathological alterations were assessed. Sb exposure significantly impaired cognitive performance, which was associated with increased oxidative stress (↑ lipid peroxides and ↓ glutathione), cholinergic dysfunction (↓ acetylcholinesterase), neuroinflammation (↑ myeloperoxidase, ↑ IL-6, and ↑ TNF-α and ↓ IL-10), disturbed mitochondrial enzyme functions (↓ complex I, II, and IV), reduced neurotrophin levels (↓ BDNF and ↓ CREB), and neuronal damage. Montelukast significantly (p ≤ 0.05) attenuated these alterations and improved behavioural function compared with the Sb-treated group. The findings suggest that montelukast can reduce Sb-induced neurotoxic alterations in mice, likely through regulating oxidative stress, neuroinflammatory responses, and mitochondrial enzyme dysfunction. However, these findings are derived from a preclinical mouse model. Further mechanistic studies and clinical trials are required to validate these findings and evaluate their translational implications.