Hepatoprotection of D-galactosamine-induced toxicity in mice by purified fractions from Garcinia kola seeds.
The hepatoprotective effect of a biflavonoid complex, kolaviron, and its fractions from Garcinia kola seeds, together with the possible mechanisms involved was investigated in mice intoxicated with a single dose of D-galactosamine (GalNH(2)). Likewise, the ability of vitamin E to attenuate the toxicity was examined. Kolaviron, was separated by thin-layer chromatographic technique into three fractions; Fraction I, Fraction II and Fraction III with RF values of 0.48, 0.71 and 0.76, respectively. Pretreatment with kolaviron, fraction I and fraction II at a dose of 100 mg/kg for seven consecutive days before challenge with a single dose of GalNH(2) (800 mg/ kg) significantly (P<0.05) decreased serum alanine (ALT) and aspartate (AST) aminotransferases by 67%, 70%, 71% and 39%, 35%, 46%, respectively over GalNH(2)-only intoxicated mice. Vitamin E elicited respectively 65% and 39% reduction in the GalNH(2)-induced increase in the activities of these enzymes. In addition, pretreatment with kolaviron and fraction II significantly (P<0.05) decreased the activity of microsomal gamma-glutamyl transferase (gamma-GT) by 42% and 46%, respectively. Administration of kolaviron to GalNH(2)-intoxicated mice also restored glucose-6-phosphatase to level that was comparable to the control (P<0.05). These extracts except fraction III prevented the accumulation of serum and microsomal lipid peroxidation products, and also prevented the depletion of reduced glutathione (GSH) levels in the liver of GalNH(2)-intoxicated mice. Kolaviron, fraction I and fraction II at a dose of 100 mg/kg caused an induction of glutathione-S-transferase (GSH transferase) and uridyl glucuronosyl transferase (UDPGT) activities by 31%, 34%, 35% and 29%, 65%, 56%, respectively. GalNH(2)-induced toxicity was essentially prevented as indicated by a liver histopathologic study of liver slices from mice pretreated with kolaviron, fraction I and fraction II. This study shows that treatment with kolaviron, fraction I and fraction II (purified fractions from Garcinia kola) appeared to enhance the recovery from GalNH(2)-induced hepatotoxicity, and that the fractions I and II may therefore be responsible for the observed antihepatotoxic effect of kolaviron. This protection may be due to the ability of these extracts to induce the expression of phase II drug metabolizing enzymes.
Adaramoye
Oluwatosin A
OA
Drug Metabolism and Toxicology Unit, Department of Biochemistry, University of Ibadan, Nigeria. aoadaramoye@yahoo.com
Adeyemi
Edward O
EO
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D005419:Flavonoids / Q000494:pharmacology*; D005688:Galactosamine / Q000633:toxicity; D029763:Garcinia kola / Q000737:chemistry; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry; D014166:Transferases / Q000378:metabolism
D005419:Flavonoids; D020011:Protective Agents; D005688:Galactosamine; D014166:Transferases; D005952:Glucose-6-Phosphatase; D005978:Glutathione; C045492:kolaviron