Role of glutathione in metabolic degradation of dichloromethane in rats.

Abstract:

:Dichloromethane (DCM) elimination and carboxyhemoglobin (COHb) generation were examined in adult female SD rats pretreated with a glutathione (GSH) depletor(s). Rats were treated with either buthionine sulfoximine (BSO; 2 mmol/kg, i.p.), diethylmaleate (DEM; 3 mmol/kg, i.p.), phorone (PHO; 1 mmol/kg, i.p.) or BSO plus PHO (BSO; 2 mmol/kg +PHO; 0.5 mmol/kg, i.p.). The hepatic GSH concentration was significantly reduced by each treatment. Decrease in hepatic GSH was maintained at least for 10 h after BSO treatment but recovered rapidly in rats treated with DEM or PHO. The hepatic p-nitrophenol hydroxylase activity was not affected by the GSH depletors at the dose used in this study. Rats were treated with an i.p. injection of DCM (3 mmol/kg) and the concentrations of DCM and the COHb levels in blood were monitored. In rats pretreated with a GSH depletor, the peak COHb level was significantly greater than that of rats treated with DCM only. The peak COHb level attained in each group of rats appeared to be inversely related to the magnitude of reduction in hepatic GSH levels. The half-life of DCM in blood was also increased in rats pretreated with the GSH depletor(s). The results indicate that the GSH-dependent metabolic reaction has an important role in the overall elimination of DCM as well as in the metabolic generation of carbon monoxide (CO) from this solvent.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Oh SJ,Kim SK,Kim YC

doi

10.1016/s0378-4274(01)00523-9

keywords:

subject

Has Abstract

pub_date

2002-03-24 00:00:00

pages

107-14

issue

1-2

eissn

0378-4274

issn

1879-3169

pii

S0378427401005239

journal_volume

129

pub_type

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