| Vanadate-induced toxicity towards isolated perfused rat livers: the role of lipid peroxidation. | |
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MedLine Citation:
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PMID: 1996468 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The toxic potential of sodium orthovanadate towards isolated perfused rat livers was investigated at a dose of 2 mmol/l. In livers from fasted rats, vanadate led to a release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH] and mitochondrial (glutamate dehydrogenase (GLDH] enzymes, an accumulation of calcium in the liver, a marked depletion of hepatic glutathione and an enhanced release of it into the perfusate, as well as an augmented formation and release of thiobarbituric acid-reactive material by the liver. Furthermore, a marked inhibition of oxygen consumption was observed. Vanadate-induced vasoconstriction resulted in a progressive decrease in perfusate flow rate. Control experiments with similarly reduced flow rates led to a comparable reduction in oxygen consumption. GPT and LDH release and hepatic glutathione depletion were also evident, though to a lesser extent than in the presence of vanadate, but no increase in GLDH release, in tissue calcium content or TBA-reactive material in the liver or the perfusate were observed. Thus, indirect toxic effects due to a reduced flow rate contribute only partly to vanadate hepatotoxicity and do not affect mitochondrial integrity. Omission of calcium from the perfusate did not prevent hepatotoxic responses to vanadate, although less calcium was present in the treated livers than in the control organs, indicating that calcium influx is not involved in vanadate-induced hepatotoxicity in the intact organ, in contrast to isolated hepatocytes. Feeding the animals, resulting in an activation of anaerobic energy conservation reactions, strongly attenuated vanadate hepatotoxicity indicating that the energetic status of the liver is the main target of vanadate. Superoxide dismutase did not affect the hepatotoxic responses of livers from fasted rats towards vanadate, while allopurinol and deferrioxamine inhibited lipid peroxidation and hepatotoxicity due to vanadate. The strong correlation between induction of lipid peroxidation and hepatotoxicity and the inhibition of both processes in parallel by antioxidants are suggestive of a causative role for lipid peroxidation in vanadate-induced hepatotoxicity. |
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Authors:
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M Younes; O Strubelt |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Toxicology Volume: 66 ISSN: 0300-483X ISO Abbreviation: Toxicology Publication Date: 1991 Feb |
Date Detail:
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Created Date: 1991-03-27 Completed Date: 1991-03-27 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 63-74 Citation Subset: IM |
Affiliation:
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Institute of Toxicology, Medical University of Lübeck, F.R.G. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alanine Transaminase
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metabolism Allopurinol / pharmacology Animals Drug Interactions Fasting Glutamate Dehydrogenase / metabolism L-Lactate Dehydrogenase / metabolism Lipid Peroxidation / drug effects* Liver / drug effects*, enzymology Male Rats Rats, Inbred Strains Superoxide Dismutase / pharmacology Vanadates / toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Vanadates; 315-30-0/Allopurinol; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.15.1.1/Superoxide Dismutase; EC 1.4.1.2/Glutamate Dehydrogenase; EC 2.6.1.2/Alanine Transaminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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