A novel biologically active selenoorganic compound—IV: Protective glutathione-dependent effect of PZ 51 (Ebselen) against ADP-Fe induced lipid peroxidation in isolated hepatocytes

Abstract

PZ 51 (Ebselen) is capable of inhibiting ADP-Fe-induced lipid peroxidation in isolated hepatocytes, assessed by generation of low-level chemiluminescence, and the formation of alkanes (ethane, n-pentane) and malondialdehyde. The sulphur analog PZ 25 is much less active. PZ 51 is ineffective in glutathione-depleted hepatocytes that were obtained after phorone pretreatment of the animals. However, other antioxidants, like (+)-cyanidanol-3 or diethyldithiocarbamate are effective in inhibiting lipid peroxidation also in glutathione-depleted cells. The results are attributed to a GSH peroxidase-like activity of PZ 51. Addition of the chemically synthetized compound, PZ 51-SG. a glutathione adduct of PZ 51, does not provide extra protection in GSH-depleted cells in comparison to the parent compound, PZ 51. Dithioerythritol exhibits a protective effect, and PZ 51 is more efficient than in the absence of this thiol reductant. Dithioerythritol also exerts an effect in glutatioone-depleted cells. A peroxidase-like activity using DTE as reductant is demonstrated in vitro.