Effect of eugenol on drug-metabolizing enzymes of carbon tetrachloride-intoxicated rat liver.
The chemoprotection extended by eugenol against carbon tetrachloride (CCl4) intoxication was established by studies on drug-metabolizing phase I and phase II enzymes. An overall decrease in drug-metabolizing enzymes, namely NADPH-cytochrome c reductase, NADH-cytochrome reductase, coumarin hydroxylase, 7-ethoxy coumarin-O-deethylase, UDP-glucuronyltransferase and glutathione-S-transferase, was observed with CCl4 intoxication, with a subsequent decrease in cytochrome P450 and cytochrome b5 content. CCl4 caused a significant decrease in microsomal phospholipids and the marker enzymes glucose-6-phosphatase and 5'-nucleotidase, and an increase in thiobarbituric acid reactive substances (TBARS). Simultaneous administration of eugenol with CCl4 inhibited the accumulation of TBARS and the decrease in the microsomal phospholipids and marker enzymes. Further, the chemical onslaught imposed by CCl4 on the drug-metabolizing system was removed successfully by eugenol. Eugenol appears to act as an in vivo antioxidant and as a better inducer of phase II enzymes than phase I enzymes. It is therefore suggested that eugenol could be an interesting basic structure for drug design.
Kumaravelu
P
P
Department of Biochemistry, University of Madras, India.
Dakshinamoorthy
D P
DP
Subramaniam
S
S
Devaraj
H
H
Devaraj
N S
NS
D015720:5'-Nucleotidase / Q000032:analysis; D015660:7-Alkoxycoumarin O-Dealkylase / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology*; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D003579:Cytochrome Reductases / Q000032:analysis; D042966:Cytochrome-B(5) Reductase; D005054:Eugenol / Q000494:pharmacology*; D005952:Glucose-6-Phosphatase / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000032:analysis; D009245:NADH Dehydrogenase / Q000032:analysis; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances
D000975:Antioxidants; D010743:Phospholipids; D017392:Thiobarbituric Acid Reactive Substances; D005054:Eugenol; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase; D009245:NADH Dehydrogenase; D015720:5'-Nucleotidase; D005952:Glucose-6-Phosphatase