Effect of garcinol against arsenic-induced neurobehavioral alterations and liver and kidney dysfunction in albino mice

Prolonged exposure to inorganic arsenic is commonly linked to brain damage via oxidative and apoptotic processes. The compound garcinol (GCL) has garnered significant interest because of its beneficial effects on human health. However, the protective ability of GCL against arsenic-induced toxicity in the brain remains unexplored. Therefore, our study aimed to examine the neuroprotective effect of GCL against the adverse impact of sodium arsenite (SA) on behavioral patterns, molecular mechanisms, apoptotic markers, and oxidative stress parameters in the brain, liver, and kidneys of mice. The mice were categorized into four distinct groups for 28 days: Group I, referred to as the Control group, received a 5 % v/v solution of dimethyl sulfoxide (DMSO); Group II, referred to as the SA group, received a dosage of 20 mg/kg of SA; Group III, referred to as the SA + GCL group, received a combined dosage of 20 mg/kg of SA and 50 mg/kg of GCL; and Group IV, referred to as the GCL group, received a dosage of 50 mg/kg of GCL. Following drug administration, the behavior of the animals was evaluated and analyzed. Additionally, the levels of acetylcholinesterase (AChE), ATP hydrolysis, and angiotensin I-converting enzyme (ACE), which are associated with cognitive function, were examined. Our study demonstrated that the administration of GCL enhanced cognitive behavior. Additionally, GCL mitigated cholinergic deficits as evidenced by a reduction in AChE activity. Furthermore, GCL increased the signaling of glycogen synthase kinase 3 beta (GSK3β) and cAMP response element-binding protein (CREB) in SA-treated mice, enhanced redox equilibrium, and protected against oxidative damage caused by SA in the brains of mice. This effect was mediated by the activation of nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) proteins, resulting in a significant decrease in malondialdehyde concentration. Thus, this preclinical study showed that treatment with GCL ameliorated neurobehavior, modulated cognitive function-associated biomarkers, and protected mice from SA-induced neurotoxicity.