Protection by Osbeckia aspera against carbon tetrachloride-mediated alterations in microsomal drug metabolizing enzyme activity.
Previous investigations have confirmed the protective effect of Osbeckia aspera leaf extract on carbon tetrachloride-mediated liver injury in rat models. It is well known that the earliest alterations in liver cell structure and function following carbon tetrachloride poisoning involve the endoplasmic reticulum and its drug metabolizing enzymes. Therefore, we investigated whether an aqueous leaf extract of O. aspera could offer protection against carbon tetrachloride-induced changes in the microsomal drug metabolizing enzymes aniline hydroxylase and p-aminopyrine N-demethylase. This enzyme activity was compared with phenobarbital-induced righting reflex and lipid peroxidation. Treatment of rats with the aqueous leaf extract of O. aspera (before or after the administration of carbon tetrachloride) resulted in a marked decrease in carbon tetrachloride-mediated alterations in aniline hydroxylase and p-aminopyrine N-demethylase activity, phenobarbital-induced loss of righting reflex and malondialdehyde formation due to lipid peroxidation. The Km value of these enzymes in control and Osbeckia-treated rats were the same. These results show that the plant extract can markedly decrease the carbon tetrachloride-mediated reduction in aniline hydroxylase and p-aminopyrine N-demethylase activity and inhibit peroxidative damage to the cell membrane. Phenobarbital-induced sleeping time in rats and kinetic enzyme studies suggested that the effects of the plant extract was neither due to an induction of the drug-metabolizing enzymes under investigation, nor due to an alteration in the Km values of these enzymes.
Jayatilaka
K A
KA
Department of Biochemistry, Faculty of Medicine, University of Ruhuna, Sri Lanka.
Thabrew
M I
MI
D000633:Aminopyrine N-Demethylase / Q000187:drug effects / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008519:Medicine, Traditional; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects
D010936:Plant Extracts; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase