title: Lipid peroxidation, protein thiols and calcium homeostasis in bromobenzene-induced liver damage.
abstract: The mechanisms of bromobenzene hepatotoxicity in vivo were studied in mice. The relationships among glutathione (GSH) depletion, lipid peroxidation, loss of protein thiols, disturbed calcium homeostasis and liver necrosis were investigated. Liver necrosis (as estimated by the serum glutamate-pyruvate transaminase (SGPT) level) appeared between 9 and 12 hr and increased at 18 hr. Lipid peroxidation which was already detectable at 6 hr in some animals, increased thereafter showing a good correlation with the severity of liver necrosis. Despite a quite fast depletion of hepatic GSH, a significant decrease in protein thiols could be observed at 12-18 hr only. Loss of protein thiols in both whole liver and subcellular fractions (microsomes and mitochondria) was correlated with lipid peroxidation. Also a good inverse correlation was seen between lipid peroxidation and the calcium sequestration activity of liver microsomes and mitochondria. The treatment of mice with desferrioxamine (DFO) after bromobenzene-intoxication completely prevented lipid peroxidation, loss of protein thiols and liver necrosis in the animals sacrificed 15 hr after poisoning. When, however, the animals were examined at 24 hr, although the general correlation between lipid peroxidation and liver necrosis was held, in some animals (about 30% of the survivors) elevation of SGPT was observed in the virtual absence of lipid peroxidation. It seems likely therefore that the liver damage seen during the first phase of bromobenzene-intoxication is strictly related to lipid peroxidation. It is, however, possible that in some animals in which for some reason lipid peroxidation does not develop, another mechanism of liver necrosis unrelated to lipid peroxidation occurs at later times.
authors: Istituto di Patologia Generale dell'Università di Siena, Italy.
authors: A F
authors: AF
authors: Casini
authors: E
authors: E
authors: Maellaro
authors: A
authors: A
authors: Pompella
authors: M
authors: M
authors: Ferrali
authors: M
authors: M
authors: Comporti
mesh_terms: D000818:Animals; D001969:Bromobenzenes / Q000378:metabolism / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis; D006706:Homeostasis / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D011506:Proteins / Q000032:analysis*; D013438:Sulfhydryl Compounds / Q000032:analysis*
chemical_list: D001969:Bromobenzenes; D008054:Lipid Peroxides; D011506:Proteins; D013438:Sulfhydryl Compounds; C032036:bromobenzene; D005978:Glutathione; D003676:Deferoxamine; D002118:Calcium