EARLY CARDIAC DAMAGE FOLLOWING SINGLE AND COMBINED EXPOSURE TO LITHIUM CARBONATE AND LEAD ACETATE IN RATS: A TOXICOLOGICAL PERSPECTIVE

Environmental contamination by heavy metals, especially lithium (Li) and lead (Pb), is of growing concern due to their increasing industrial applications and accumulation in ecosystems. This study investigated the cardiotoxic and systemic effects of individual and combined oral exposure to lithium carbonate and lead acetate in forty-eight adult male rats over a 28-day period. Animals were assigned to four groups: control, Li (20 mg/kg), Pb (20 mg/kg), and Li + Pb (20 mg each/kg). All toxicity groups exhibited clinical signs such as dullness, dehydration, diarrhea, hair loss, and foul-smelling feces. Electrocardiographic (ECG) abnormalities, including shortening of QRS duration, changes in P- and T-wave amplitudes, and sporadic atrial flutter in a few animals, suggest the presence of cardiac dysrhythmia in the treatment groups. Although no significant changes in heart weights or indices were observed, the Li + Pb group showed significantly elevated levels of malondialdehyde (MDA) and nitric oxide (NO), alongside decreased total antioxidant capacity (TAC), suggesting oxidative stress. No significant change was observed in the antioxidant enzyme (SOD, CAT, and GSH) level in the treatment groups. Molecular analysis revealed downregulation of nrf2 and bcl-2, and upregulation of bax in the Li + Pb group, suggesting increased apoptosis and reduced cell survival. Interestingly, Pb alone upregulated bcl-2 more than Li, indicating a differential stress response. Histological examination showed no overt structural damage to myocardial tissue. These findings indicate that co-exposure to Li and Pb exerts synergistic cardiotoxic effects primarily via oxidative stress and apoptosis, warranting attention to combined environmental exposures in public health assessments.