ACTIVITY OF Rosmarinus officinalis IN THE HIPPOCAMPUS OF LEAD ACETATE-EXPOSED RATS

Hippocampal dysfunction is a key feature of several neurocognitive disorders and may arise from factors such as congenital defects, neurodegeneration, or exposure to neurotoxicants. Lead (Pb), a potent heavy metal, crosses the blood-brain barrier and accumulates in the hippocampus, where it disrupts calcium signaling and induces oxidative stress, thus contributing to neuronal damage and cognitive deficits. Evidence suggests that dietary antioxidants may help mitigate Pb-induced oxidative damage and preserve hippocampal function. Accordingly, this study investigated the protective activity of aqueous Rosmarinus officinalis leaf extract (R. officinalis) against lead acetate (PbA) induced hippocampal toxicity. Forty-eight (48) adult Wistar rats were randomly assigned into six groups (A-F). Group A served as control; Group B received 100 mg/kg body weight [bw] of PbA only; Group C received 100 mg/kg bw of R. officinalis extract and PbA; Group D received 200 mg/kg bw of R. officinalis extract and PbA; Group E received 100 mg/kg bw of R. officinalis extract only and Group F received 200 mg/kg bw of R. officinalis extract only. All administrations, via an orogastric tube, lasted for twenty-eight (28) days. Thereafter, neurobehavioral activities were evaluated using the Novel object recognition, Y-maze and Elevated plus maze tests. Following the sacrifice of the experimental rats, the hippocampi were collected for Pb concentration, antioxidant enzymes activity, lipid peroxidation, acetylcholinesterase activity, nitric oxide levels, and histological assessments as well as apoptosis. The findings showed that PbAexposed rats exhibited significant (p<0.05) weight loss, cognitive and memory impairments, dysregulated antioxidant enzymes activity, and increased lipid peroxidation, nitric oxide, Pb and AChE levels, along with atrophy and vacuolation of pyramidal cells and astrocytes in the CA1 region of the hippocampus. Also, there was an upregulation of Caspase-3 expression in the hippocampus of experimental rats exposed to PbA, indicating apoptosis as a possible mechanism of action. However, pretreatment with R. officinalis significantly (p<0.05) mitigated the adverse effects induced by PbA in the hippocampus of experimental rats suggesting strong metal-chelating, anti-cholinesterase, and NO-scavenging effects. Similarly, the downregulation of caspase-3 expression in the hippocampus of PbA-exposed rats following pretreatment with R. officinalis supports its anti-apoptotic potential. Overall, these findings suggest that R. officinalis exhibits potent antioxidant, metal-chelating, nitric oxide-scavenging, anti-cholinesterase and anti-apoptotic properties, thus providing novel evidence supporting R. officinalis as a promising neuroprotective agent with potential for drug development against hippocampal dysfunction.