Article date: September 1999
By: Ahmed Galal, Patrick Du Souich, in Volume 128, Issue 2, pages 374-379
This study was conducted to assess whether a 21‐aminosteroid, U74389G, could prevent the down‐regulation of hepatic cytochrome P450 (P450) induced by acute moderate hypoxia or an inflammatory reaction.
The rabbits of two groups (n=6 per group) were subjected to acute moderate hypoxia (PaO2∼35 mmHg), one pre‐treated with U74389G (3 mg kg−1 i.v. every 6 h, for 48 h). The rabbits of two other groups received 5 ml of turpentine s.c., one of them being pre‐treated with U74389G (3 mg kg−1 i.v. every 6 h, for 72 h). The kinetics of theophylline (2.5 mg kg−1) were assessed to evaluate the activity of the P450. Once the rabbits were sacrificed, the P450 content and the amount of thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, were estimated in the liver.
Compared with control rabbits, hypoxia and inflammation increased theophylline plasma concentrations, as a result of a decrease in theophylline systemic clearance (P<0.05). Both experimental conditions reduced hepatic content of P450 by 40–50% (P<0.05) and increased the amount of hepatic TBARS by around 50% (P<0.05). Pre‐treatment with U74389G prevented the hypoxia‐ and inflammation‐induced decrease in theophylline systemic clearance, the down‐regulation of hepatic P450, and the increase in liver TBARS.
It is concluded that in the rabbit, U74389G prevents hepatic P450 depression produced by acute moderate hypoxia and a turpentine‐induced inflammatory reaction, possibly by eliciting a radical quenching antioxidant activity.
This study was conducted to assess whether a 21‐aminosteroid, U74389G, could prevent the down‐regulation of hepatic cytochrome P450 (P450) induced by acute moderate hypoxia or an inflammatory reaction.
The rabbits of two groups (n=6 per group) were subjected to acute moderate hypoxia (PaO2∼35 mmHg), one pre‐treated with U74389G (3 mg kg−1 i.v. every 6 h, for 48 h). The rabbits of two other groups received 5 ml of turpentine s.c., one of them being pre‐treated with U74389G (3 mg kg−1 i.v. every 6 h, for 72 h). The kinetics of theophylline (2.5 mg kg−1) were assessed to evaluate the activity of the P450. Once the rabbits were sacrificed, the P450 content and the amount of thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, were estimated in the liver.
Compared with control rabbits, hypoxia and inflammation increased theophylline plasma concentrations, as a result of a decrease in theophylline systemic clearance (P<0.05). Both experimental conditions reduced hepatic content of P450 by 40–50% (P<0.05) and increased the amount of hepatic TBARS by around 50% (P<0.05). Pre‐treatment with U74389G prevented the hypoxia‐ and inflammation‐induced decrease in theophylline systemic clearance, the down‐regulation of hepatic P450, and the increase in liver TBARS.
It is concluded that in the rabbit, U74389G prevents hepatic P450 depression produced by acute moderate hypoxia and a turpentine‐induced inflammatory reaction, possibly by eliciting a radical quenching antioxidant activity.
British Journal of Pharmacology (1999) 128, 374–379; doi:10.1038/sj.bjp.0702796
DOI: 10.1038/sj.bjp.0702796
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