LAUSR

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.