Hepatoprotection by Dimethyl Sulfoxide: III. Role of Inhibition of the Bioactivation and Covalent Binding of Chloroform

作者: Richard C. Lind , Carmen K. Begay , A.Jay Gandolfi

DOI: 10.1006/TAAP.2000.8949

关键词: StereochemistryLiver injuryPharmacologyToxicityAntidoteDimethyl sulfoxideAlanine transaminaseHepatoprotectionChemistryEnzymeChloroform

摘要: Abstract Dimethyl sulfoxide (DMSO) has previously been shown to have the ability attenuate chloroform (CHCl 3 )-induced liver injury in naive rat even when administered 24 h after toxicant. These studies were undertaken determine if protective action by late administration of DMSO is due an inhibition bioactivation CHCl . This was done comparing cytochrome P450 inhibitors, diallyl sulfide (DAS), and aminobenzotriazole (ABT) for their efficacy exposure. In addition, 14 utilized measure effect ABT on covalent binding following administration. Male Sprague–Dawley rats (300–350 g) received 0.75 ml/kg po. Twenty-four hours later, they ip injection 2 DMSO, 100 mg/kg DAS, or 30 ABT. Plasma ALT activities quantitation light microscopy at 48 dosing indicated that all three treatments equally effective protecting liver. A detailed study time course development occurring within 10 its Therefore, radiolabel studies, killed 24–34 receiving (30 μCi/kg ) Treatment with decreased C hepatic protein 35% reduced amount blood 50% treatment did not significantly affect any these parameters. The lack would indicate may offer protection mechanisms other than also specific inhibitors be benefit clinical situations help treat delayed onset hepatitis can result poisoning organohalogen, antidotes are a number initial

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