Induction of heme oxygenase-1 with β-CD-hemin complex mitigates cadmium-induced oxidative damage in the roots of Medicago sativa

Using pharmacological and biochemical approaches, the functional roles of heme oxygenase-1 (HO-1) induction in cadmium (Cd)-stressed alfalfa (Medicago sativa) seedling roots caused by a metal-organic complex (β-cyclodextrin-hemin, β-CD-hemin, CDH) and the well-known HO-1 inducer hemin, were investigated and compared. Cd-stressed seedling roots exhibited severe oxidative damage, whereas up-regulation of HO-1 by CDH and hemin pretreatment prevented this toxic response, as evidenced by the decrease of lipid peroxidation as well as the alleviation of growth inhibition and Cd accumulation. Reestablishment of glutathione (GSH) and reactive oxygen species (ROS) homeostasis were observed. Upon Cd stress, 0.01 μM CDH and 10 μM hemin pretreatment alleviated lipid peroxidation to almost the same extent and the CDH was highly potent. The modulation of the transcripts and total activities of ascorbate peroxidase (APX) and superoxide dismutase (SOD) were regulated by CDH and hemin, respectively. We also noticed that the potent HO-1 inhibitor zinc protoporphyrin IX (ZnPP) significantly reversed the CDH-driven cytoprotective roles. Additionally, β-CD was found to be ineffective in the alleviation of lipid peroxidation. Taken together, the data suggested that HO-1 induction mediated by CDH provides critical protection against Cd-induced oxidative damage and toxicity partly by lowering the Cd accumulation.