Silymarin effects on intracellular calcuim and cytotoxicity: a study in perfused rat hepatocytes after oxidative stress injury.
The re-emergence of silymarin as a natural remedy for diseases of the liver and biliary tract necessitates reevaluation of the efficiency of this compound and its possible mode of action. The aim of this study was to investigate the potentials of silymarin on the amelioration of hepatic injuries. The possible mechanism(s) that contribute to the hepatoprotective effect of silymarin and the role played by intracellular calcium (Ca(2+)(i)) was investigated using tert-butyl hydroperoxide (TBH) and D-galactosamine (D-Gal) intoxication in a model of the isolated immobilized and perfused hepatocytes. Silymarin decreased lactate dehydrogenase (LDH) leakage, increased oxygen consumption, reduced the formation of lipid peroxides (malondialdehyde, MDA) in hepatocytes that were altered by TBH and increased urea synthesis in the perfusion medium. TBH treatment increased Ca(2+)(i) in hepatocytes significantly to a value of more than 600 nM and silymarin pre-treatment reduced the TBH-induced rise in Ca(2+)(i) and brought Ca(2+)(i) level to below 300 nM. Silymarin did not affect LD leakage or urea synthesis in D-Gal-injured cells. It is concluded that silymarin hepatoprotective effect under the present experimental conditions is due to the inhibition of lipid peroxidation and that the modulation of hepatocyte Ca(2+)(i) plays a pivotal role in a protective effect.
Farghali
H
H
Institute of Pharmacology, First Faculty of Medicine, Charles University, Albertov 4, Prague 2, 128 00, Czech Republic.
Kameniková
L
L
Hynie
S
S
Kmonicková
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects*; D018914:Cells, Immobilized; D003080:Cold Temperature; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology*; D014508:Urea / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000633:toxicity
D012838:Silymarin; D014508:Urea; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D002118:Calcium