title: Cyclosporin A protects hepatocytes subjected to high Ca2+ and oxidative stress.
abstract: Hepatocytes incubated with 0.8 mM t-butylhydroperoxide are protected by cyclosporin A when the medium Ca2+ concentration is 10 mM, but not when it is 2.5 mM. The highest Ca2+ level is associated with an inhibition of t-butylhydroperoxide-dependent malondialdehyde accumulation and with mitochondrial Ca2+ loading within the cells. These findings are new evidence that t-butylhydroperoxide can kill cells by peroxidation-dependent and -independent mechanisms, and suggest that the mitochondrial permeability transition and the resultant de-energization are components of the peroxidation-independent mechanism. Cyclosporin A may have considerable utility for the protection of cells subjected to oxidative stress.
authors.affiliation: Hormel Institute, University of Minnesota, Austin 55912.
authors.forename: K M
authors.initials: KM
authors.lastname: Broekemeier
authors.forename: L
authors.initials: L
authors.lastname: Carpenter-Deyo
authors.forename: D J
authors.initials: DJ
authors.lastname: Reed
authors.forename: D R
authors.initials: DR
authors.lastname: Pfeiffer
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008930:Mitochondria, Liver / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D020122:tert-Butylhydroperoxide
chemical_list: D016877:Oxidants; D010545:Peroxides; D008315:Malondialdehyde; D016572:Cyclosporine; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D002118:Calcium