title: In vivo and in vitro inhibition of rat liver glutathione transferases activity by extracts from Combretum zeyheri (Combretaceae) and Parinari curatellifolia (Chrysobalanaceae).
abstract: BACKGROUND
  Parinari curatellifolia and Combretum zeyheri are medicinal plants used in Zimbabwe and other Southern African countries for stomach ailments, fever, body aches, wound healing, cancer and tuberculosis. Glutathione transferases (GSTs) are mammalian enzymes that play a significant role in the detoxification and metabolism of many xenobiotic and endogenous compounds and as such can interact with many exogenous compounds including herbal medicines. The effects of Parinari curatellifolia and Combretum zeyheri leaf extracts on glutathione transferases of male Sprague-Dawley rats were investigated in vivo and in vitro after oral administration of either leaf ethanol or water extracts of each plant.
  
  
  METHODS
  For Parinari curatellifolia, 18 male Sprague-Dawley rats were administered with 0, 500 and 1000 mg/kg body weight of the leaf extracts in corn oil or saline. Animals were sacrificed after 96 h and the kidney and liver samples were removed and used to prepare the cytosolic fractions. GST activity was determined using 1-chloro-2, 4-dinitrobezene. For Combretum zeyheri, twenty four male Sprague-Dawley rats were randomly divided into two groups. These two groups were further divided into three groups of four animals each. They were given either the aqueous or ethanol extract at doses of C. zeyheri at 0, 50 mg/kg body weight and 200 mg/kg body weight. The extracts were administered orally by oral gavage for four consecutive days and the rats were sacrificed by cervical dislocation on the fifth day.
  
  
  RESULTS
  In animals administered with C. zeyheri, GST activity was significantly increased by the 200 mg/kg aqueous extract in the kidneys and livers in vivo whilst the ethanolic extract at 200 mg/kg decreased enzyme activity significantly both organs. Both the ethanol and aqueous extracts inhibited GST activity in vitro with the ethanol extract being more potent inhibitor than ethacrynic acid, a standard GST inhibitor. The increased GST activity in vivo and versus inhibition in vitro suggests that metabolites may be responsible for the effects observed in vivo. For P. curatellifolia, a dose-dependent decrease in GST activity was observed in vivo for the animals given the aqueous extract but no changes were observed with the ethanol extract. There was a concentration-dependent inhibition of cytosolic GSTs when P. curatellifolia leaf extracts in vitro. The ethanol extract of P. curatellifolia exhibited GST-inhibitory activity in the liver with an IC50 value of 12 μg/mL and for ethacrynic acid, the IC50 was found to be 10 μg/mL. This showed that this extract was a potent inhibitor of GSTs in vitro.
  
  
  CONCLUSIONS
  C. zeyheri had an inductive effect on GST activity when administered in aqueous solution but inhibited GST in vitro whilst P. curatellifolia inhibited GST activity in vivo. Induction of GSTs would be cytoprotective against the toxic effects electrophilic chemicals. Since GSTs are responsible for the synthesis of prostaglandins, the inhibition of GST activity of by these two plants in vivo maybe one of the reasons that makes the plants important for use in the treatment pain and fever in ethnopharmacology.
authors.affiliation: School of Pharmacy, College of Health Sciences, University of Zimbabwe, Mt. Pleasant, Harare, Zimbabwe.
authors.forename: David
authors.initials: D
authors.lastname: Gweshelo
authors.affiliation: Biomolecular Interactions Analyses Group, Department of Biochemistry, University of Zimbabwe, P.O. Box MP 167, Mt. Pleasant, Harare, Zimbabwe.
authors.forename: Rudo
authors.initials: R
authors.lastname: Muswe
authors.affiliation: Biomolecular Interactions Analyses Group, Department of Biochemistry, University of Zimbabwe, P.O. Box MP 167, Mt. Pleasant, Harare, Zimbabwe. smukanganyama@medic.uz.ac.zw.
authors.forename: Stanley
authors.initials: S
authors.lastname: Mukanganyama
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D045469:Chrysobalanaceae / Q000737:chemistry*; D029765:Combretum / Q000737:chemistry*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D005982:Glutathione Transferase
keywords: Glutathione transferases; Induction; Inhibition; Natural plant products; Sprague–Dawley rats