Influence of chloramphenicol on rat hepatic microsomal components and biomarkers of oxidative stress: protective role of antioxidants.
The effects of chloramphenicol and antioxidant vitamins on in vivo and in vitro indices of microsomal drug oxidizing system were examined in rats. Chloramphenicol at doses of 28 mg/kg, 57 mg/kg and 86 mg/kg body weight administered for 10 consecutive days resulted in a dose-dependent decrease in body weight, liver weight, relative liver weight and protein content compared to control. Chloramphenicol treatment also resulted in a dose-dependent decrease in microsomal phospholipid and a significant increase in cholesterol content causing an increase in cholesterol/phospholipid molar ratio. The drug produced a significant reduction in the activity of aniline hydroxylase, aminopyrine N-demethylase, p-nitroanisole O-demethylase and ethoxyresorufin O- deethylase. Activity of ethoxyresorufin O-deethylase was little affected by the drug. Chloramphenicol ranging from 10-4-10-6 M similarly produced a concentration dependent inhibition in the activities of the enzymes. Kinetic studies revealed that chloramphenicol inhibited the enzymes non-competitively. alpha-Tocopherol, beta-carotene and ascorbic acid decreased the chloramphenicol inhibition of the enzymes within the range of 70 to 81%, 45-63% and 55 to 75% respectively. Also, the antioxidant vitamins attenuated the chloramphenicol-induced formation of malondialdehyde by 60%, 53% and 56% and lipid hydroperoxide by 60%, 54%, and 54% respectively The results indicate that the effect of chloramphenicol on cytochrome P450 drug oxidizing enzyme components is related to the action of the drug presumably, via free radical mechanism and that co-administration with antioxidant vitamins can attenuate its toxic action.
Farombi
E Olatunde
EO
Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria. ofarombi@skannet.com
Adaramoye
Oluwatosin A
OA
Emerole
Godwin O
GO
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D002701:Chloramphenicol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D015415:Biomarkers; D002701:Chloramphenicol