Hepatoprotective activity of xanthones and xanthonolignoids against tert-butylhydroperoxide-induced toxicity in isolated rat hepatocytes--comparison with silybin.
OBJECTIVE
Synthesize and evaluate the protective activity against tertbutylhydroperoxide-induced toxicity in freshly isolated rat hepatocytes of trans-kielcorin, trans-isokielcorin B, as well as their respective building blocks 3,4-dihydroxy-2-methoxyxanthone and 2,3-dihydroxy-4-methoxyxanthone.


METHODS
Wistar rats, weighing 200-250g were used. Hepatocyte isolation was performed by collagenase perfusion. Incubations were performed at 37 degrees C, using 1 million cells per milliliter in modified Krebs--Henseleit buffer. The protective activity was evaluated by measuring reduced and oxidized glutathione, lipid peroxidation and cell viability after inducing toxicity with tert-butylhydroperoxide (1.0 mM, 30 min), with or without the studied compounds in the concentrations of 0.025, 0.050, 0.100 and 0.200 mM. Silybin was tested in the same experimental conditions to serve as a positive control.


RESULTS
Using these concentrations, the tested compounds prevented tert-butylhydroperoxide-induced lipid peroxidation and cell death in freshly isolated rat hepatocytes. All compounds were also effective in preventing perturbation of cell glutathione homeostasis in some extent. 3,4-Dihydroxy-2-methoxyxanthone and 2,3-dihydroxy-4-methoxyxanthone were more effective than trans-kielcorin and trans-isokielcorin B respectively. Silybin was less effective in protecting cells against lipid peroxidation and loss of cell viability than the four xanthonic derivatives.


CONCLUSIONS
The tested compounds protected the freshly isolated rat hepatocytes against tert-butylhydroperoxide-induced toxicity.
Fernandes
E R
ER
C.E.Q.O.F.F.U.P., Faculdade de Farmácia, Universidade do Porto, Portugal.
Carvalho
F D
FD
Remião
F G
FG
Bastos
M L
ML
Pinto
M M
MM
Gottlieb
O R
OR
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010545:Peroxides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014966:Xanthenes / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide
D017705:Lignans; D010545:Peroxides; D012838:Silymarin; D017392:Thiobarbituric Acid Reactive Substances; D014966:Xanthenes; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione