In vivo and in vitro effect of sulfamethazine on hepatic mixed function oxidases in rats.
Sulfamethazine (SMZ) administration (ip, 3 d) of different doses to adult male rats showed significant increases in the electron transport components and activities of aminopyrine N-demethylase and aniline hydroxylase at the the 150 mg SMZ/kg dose level. However, 300 mg SMZ/kg doses produced a significant decrease in cytochrome P-450 and the activity of aminopyrine N-demethylase. In a longer duration study, 300 mg SMZ/kg caused significant decreases in cytochrome P-450 and in the activity of aminopyrine N-demethylase. The inducer dose of 150 mg SMZ/kg and the inhibitory dose of 300 mg SMZ/kg were selected for dosing young male, old male and adult female rats. Sulfamethazine administration to young male rats resulted in a significant induction of electron transport components and drug metabolizing enzymes at both dose levels. However, SMZ treatment of old rats produced significant decreases in electron transport components and aminopryine N-demethylase activity at both dose levels. A significant induction in the levels of electron transport components was observed with 150 mg SMZ/kg in female rats. All other parameters were unchanged. Sulfamethazine resulted in a mixed type of inhibition (Ki = 3.5 mM) of aminopyrine N-demethylase in vitro. Hydroxylated metabolites destructed the spectral and catalytic activity of cytochrome P-450. Our studies suggest that SMZ is a substrate of the mixed function oxidase system and induction is dependent on dosage, age and sex of the animals.
Kodam
K M
KM
Department of Biochemistry, Shivaji University, Kolhapur, India.
Govindwar
S P
SP
D000375:Aging / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D013418:Sulfamethazine / Q000008:administration & dosage / Q000494:pharmacology*
D000890:Anti-Infective Agents; D013418:Sulfamethazine; D006899:Mixed Function Oxygenases; D000633:Aminopyrine N-Demethylase