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Late dimethyl sulfoxide administration provides a protective action against chemically induced injury in both the liver and the kidney.

Abstract：

:Dimethyl sulfoxide (DMSO) can protect the liver from injury produced by a variety of hepatotoxicants when administered prior to or concomitant with the toxicants. This protective action has previously been attributed to DMSO-induced inhibition of bioactivation of the compounds to toxic intermediates. In these studies, the ability of DMSO to provide protection when administered 10 hr after a toxicant was evaluated in several animal models of xenobiotic-induced liver and kidney injury. In the guinea pig model of halothane-associated hepatotoxicity, male outbred Hartley guinea pigs received 2 ml/kg DMSO 10 hr after an inhalation exposure to 1.0% halothane, 40% O2 for 4 hr. DMSO decreased the extent of liver necrosis as indicated by a threefold decrease in plasma alanine aminotransferase activity 48 hr after exposure and a reduction in the incidence and extent of zone 3 necrosis. These results do not appear to be due to alterations in halothane biotransformation since DMSO administered at 10 hr after halothane had no affect on plasma concentrations of the halothane metabolite tritluoroacetic acid or covalent binding by reactive halothane biotransformation intermediates to hepatic protein. In addition, administration of the structurally analogous biotransformation inhibitor diallyl sulfide at 10 hr after halothane also had no affect on biotransformation or covalent binding but provided no protection from liver injury. Hepatic glutathione concentrations in the guinea pigs 24 hr after halothane exposure were also unaffected by late treatment with DMSO. Further studies in male Sprague-Dawley rats demonstrated the ability of DMSO to decrease the hepatic injury resulting from oral administration of 1.0 ml/kg chloroform or 0.5 ml/kg bromobenzene when administered 10 hr after either toxicant. The chloroform-treated rats also developed renal tubular necrosis with large increases in plasma creatinine and urea nitrogen, which were completely ameliorated by DMSO. Elucidating the mechanism(s) of this protective action of late DMSO administration should provide insight into the cascade of events that lead to liver and kidney injury from toxicants and, hopefully, therapeutic modalities for individuals suffering from acute, progressing, xenobiotic-induced hepatitis.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Lind RC,Gandolfi AJ

doi

10.1006/taap.1996.8009

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

201-7

issue

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(96)98009-6

journal_volume

142

pub_type

杂志文章

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Late dimethyl sulfoxide administration provides a protective action against chemically induced injury in both the liver and the kidney.