A novel biologically active selenoorganic compound--IV. Protective glutathione-dependent effect of PZ 51 (ebselen) against ADP-Fe induced lipid peroxidation in isolated hepatocytes.
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 glutathione-depleted cells. A peroxidase-like activity using DTE as reductant is demonstrated in vitro.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004226:Dithioerythritol / Q000378:metabolism / Q000494:pharmacology; D004980:Ethane / Q000378:metabolism; D005978:Glutathione / Q000172:deficiency / Q000502:physiology*; D066298:In Vitro Techniques; D007501:Iron / Q000037:antagonists & inhibitors; D007659:Ketones / Q000494:pharmacology; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010420:Pentanes / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013858:Thiobarbiturates
D000975:Antioxidants; D007659:Ketones; D008054:Lipid Peroxides; D010420:Pentanes; D013858:Thiobarbiturates; C033353:pentane; D008315:Malondialdehyde; D000244:Adenosine Diphosphate; D004226:Dithioerythritol; C018637:phorone; D007501:Iron; D010544:Peroxidases; D005978:Glutathione; D004980:Ethane; C029684:thiobarbituric acid