Neurotoxic effect of lead on rats: Relationship to Apoptosis

Background: Lead toxicity has been subjected to intensive research work, but some aspects of its mechanism needs to be elucidated. Objectives: In the current study we aim to investigate the impact of lead toxicity on some different intermediates of apoptotic signaling pathway in experimental rats. Design and methods: We measured caspase-8 and caspase-9 [by chemilumenescence], Bax and Bcl-2 [by ELISA] in Experimental rats, injected intraperitoneally with lead acetate for 7days at the dosage of 25, 50 and l00 mg/kg body weight and compared to control rats injected with deionized distilled water instead. Results: Lead acetate significantly increased the levels of caspase 8, caspase 9 and Bax in liver, kidney and brain of experimental animals especially those with high doses. Meanwhile, caspase 8 and Bax significantly increased in brain tissue at low dose of lead, while Bcl-2 significantly increased only with advanced toxicity. Furthermore, Bax/ bcl2 ratio was significantly high in kidney (p<0.05), liver (p<0.01) and brain (p<0.01) at higher doses of lead toxicity. However, brain tissues showed significant Bax/Bcl2 ratio (p<0.05) at low lead dose. A significant positive correlation was noticed between the blood level of lead and enzymatic level of caspase 8, caspase 9 and Bax in different tissues. Conclusion: we concluded that lead might have toxic effect through intrinsic and extrinsic induction of apoptotic pathway with prominent effect on brain tissue even at low dose.