Biochemical Toxicology of Desmodium Adscendens
Loading...
Date
2001-09
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Ghana
Abstract
Aqueous crude extract of Desmodium adscendens, as dispensed at the Centre for Scientific Research into Plant Medicine (CSRPM), was freeze-dried into a powder and used in this study to evaluate its toxicological effects in rats. For acute toxicity studies, high doses of the freeze-dried extract, were administered orally as single doses to rats, and the behaviours of the animals and organ toxicity were noted. Low, medium and high doses of the plant extract, representing 3, 10, and 30% of the dose that caused 50% lethality over the period of observation were administered to another group of rats in subchronic toxicity studies, and certain biochemical parameters measured as indices of liver and kidney toxicity. In order to investigate possible drug-drug interaction with other drugs, the effects of the plant material on zoxazolamine paralysis time, thiopentone sleeping time and the induction/inhibition of isozymes of the cytochrome P450 (CYP) enzyme systems were studied. From the results of the acute toxicity studies, the dose of the plant extract that caused 50% lethality was estimated to be 1125mg/kg body weight and this is about 456 times the prescribed dose in humans. When the extract was chronically administered, no significant differences were observed in levels of γ-glutamyltransferase activity, total protein, total bilirubin, creatinine and blood urea nitrogen concentrations in sera of test and control animals, irrespective of the doses of the extract administered. There were however increases in alanine and aspartate aminotransferase activities, and direct bilirubin concentration with increasing dose levels of the plant extract. Suggesting a possible hepatocellular damage, and hepatic excretory dysfunction or increased RBC haemolysis respectively. The plant extract caused a decrease in zoxazolamine paralysis time and prevented thiopentone from causing sleep in test animals as compared to controls. Results of the studies on the hepatic microsomal CYP isozymes suggest that CYP2B1/2B2 are involed in the metabolism of zoxazolamine and thiopentone. This study has indicated that the doses that caused lethality are much higher than the effective therapeutic dose of the extract of D. adscendens. Chronic administration also showed minimal signs of hepatotoxicity at doses 15-150 times higher than the effective therapeutic dose, suggesting that the plant extract may be safe at the therapeutic dose. Thus although D. adscendens may be safe, its induction of CYP2B1/2B2 and inhibition of CYP2E suggest that when the plant extract is co-administered with other drugs, may lead to possible drug interaction which may cause increase in /loss of therapeutic effectiveness or toxicity of the co-administered drug.