Hemin provides protection against lead neurotoxicity through heme oxygenase 1/carbon monoxide activation

The neurotoxicity of lead (Pb) is well established, and oxidative stress is strongly associated with Pb-induced neurotoxicity. Heme oxygenase 1 (HO-1) is an important antioxidative enzyme for protection against oxidative stress in many disease models. In this study, we applied hemin, the substrate and a well-known inducer of HO-1, to investigate the possible role of HO-1 in protecting against Pb neurotoxicity. Hemin can significantly attenuate Pb acetate-induced cell death and oxidative stress in the hippocampus and frontal cortex of developmental rats. Consistent with in vivo results, the protective effects of hemin were also observed in SH-SY5Y cells after inducing cell survival and maintaining redox balance. However, knocking down HO-1 could significantly abolish the cytoprotective action of hemin against Pb toxicity, confirming HO-1 contributed to the protection. Finally, the HO-1-derived production of carbon monoxide, but not of bilirubin or Fe²⁺, mediated the protective effects of HO-1 activation induced by hemin treatment against Pb-induced cell death and oxidative stress in SHSY5Y cells. Overall, this study showed that hemin provided protection against Pb neurotoxicity by HO-1/carbon monoxide activation.