Hypericum androsaemum infusion increases tert-butyl hydroperoxide-induced mice hepatotoxicity in vivo.
Increasing evidence regarding free radical generating agents indicates that the sustained production of high levels of reactive oxygen species (ROS) can cause hepatotoxicity. Being a short chain analog of lipid peroxide, tert-butyl hydroperoxide (t-BHP) is metabolized into free radical intermediates by cytochrome P450 in hepatocytes, which initiate lipid peroxidation, glutathione depletion and cell damage. The aim of the present study was to evaluate the putative protective effect of Hypericum androsaemum lyophilised infusion against t-BHP-induced mice hepatotoxicity in vivo, which has already been shown to be antioxidant in vitro. However, the results showed that the oral pretreatment with Hypericum androsaemum infusion (4, 20 and 100 mg/kg) for 4 days before a single intraperitoneal dose of t-BHP (1.8 mmol/kg) potentiated the t-BHP-induced hepatotoxicity. In fact, it was observed a potentiation in the depletion of total glutathione and reduced glutathione (GSH) contents and increase in oxidised glutathione (GSSG) level. Also the histopathological evaluation of the mice livers revealed that the infusion raised the incidence of liver lesions induced by t-BHP. These data do not corroborate any effect of Hypericum androsaemum infusion as hepatoprotector, but rather as a potentiator of hepatotoxicity in the present experimental conditions.
Department of Pharmacognosy, University of Porto, Rua Aníbal Cunha, 4050-047, Portugal.
Patrícia
P
Valentão
Márcia
M
Carvalho
Félix
F
Carvalho
Eduarda
E
Fernandes
Ricardo Pires
RP
das Neves
M Lourdes
ML
Pereira
Paula B
PB
Andrade
Rosa M
RM
Seabra
M Lourdes
ML
Bastos
D000818:Animals; D020902:Hypericum; D007262:Infusions, Intravenous; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity; D018515:Plant Leaves; D020122:tert-Butylhydroperoxide / Q000008:administration & dosage* / Q000302:isolation & purification / Q000633:toxicity*
D010936:Plant Extracts; D020122:tert-Butylhydroperoxide