Effect of alpha-methyldopa on pentoxyresorufin O-dealkylation in liver microsomes from rats treated with phenobarbital.
Loss of pentoxyresorufin O-dealkylation (PROD) was observed when microsomes from PB-treated rats were preincubated in the presence of NADPH. PROD proved to be quite sensitive towards inactivation. Decrease in cytochrome P450 (CYP) dependent activity was accompanied by simultaneous formation of thiobarbituric acid reactive substances (TBARS) indicating the occurrence of lipid peroxidation. The presence of 50 microM alpha-methyldopa (AMD) during preincubation with NADPH resulted in complete protection against enzyme activity loss and the extent of lipid peroxidation was also diminished. Addition of ascorbate or GSH in combination with AMD reduced the protective effect of the drug on PROD. AMD probably exerts its effect by scavenging reactive oxygen species but chelation of ferric ions can also contribute to the protective effect of the drug on PROD activity.
Veres
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Department of Biochemical Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeri út 59-67, H-1525 Budapest, Hungary. veres@chemres.hu
Szakács
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T
Vereczkey
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L
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D019362:Cytochrome P-450 CYP2B1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004298:Dopamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008750:Methyldopa / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010078:Oxazines / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors; D010078:Oxazines; D007980:Levodopa; D009249:NADP; D008750:Methyldopa; C044943:pentoxyresorufin; D019362:Cytochrome P-450 CYP2B1; D005978:Glutathione; D001205:Ascorbic Acid; D004298:Dopamine; D010634:Phenobarbital