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Protection of rats against the effects of alpha-naphthylthiourea (ANTU) by elevation of non-protein sulphydryl levels.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 1991 Aug 22; Vol. 42 (6), pp. 1203-8. - Publication Year :
- 1991
-
Abstract
- We have investigated the influence of the elevation of pulmonary glutathione (GSH) levels on the toxicity of the rodenticide alpha-naphthylthiourea (ANTU) to rat lung. Administration of phorone (diisopropylidene acetone; 200 mg/kg i.p.) caused an initial depletion of both pulmonary and hepatic GSH followed after 48 hr by a marked elevation in both tissues, due most probably to a compensatory rebound synthesis. In control rats, ANTU produced a dose-dependent lethality, hydrothorax and loss of ability of lung tissue to accumulate adenosine and spermidine (markers of endothelial and epithelial cell function, respectively). These effects were prevented or markedly ameliorated when ANTU was given 48 hr after pretreatment with phorone. The mechanism of the protection by phorone pretreatment against ANTU-induced pulmonary toxicity is unclear. It may be due, in part, to elevated GSH levels in pulmonary endothelial cells and, in addition, to increased detoxification of ANTU in the liver, resulting in a decreased availability to the lung.
- Subjects :
- Adenosine metabolism
Animals
Liver metabolism
Lung metabolism
Male
Paraquat toxicity
Rats
Rats, Inbred Strains
Spermidine metabolism
Thiourea antagonists & inhibitors
Thiourea toxicity
Glutathione metabolism
Ketones pharmacology
Liver drug effects
Lung drug effects
Thiourea analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2952
- Volume :
- 42
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 1909526
- Full Text :
- https://doi.org/10.1016/0006-2952(91)90255-4