Primary cultures of human hepatocytes as a tool in cytotoxicity studies: cell protection against model toxins by flavonolignans obtained from Silybum marianum.
The aim of this study was to evaluate the cytoprotective effects upon primary human hepatocytes of silymarin extract and its main flavonolignans following exposure to the cytotoxic actions of model toxins. The conditions for the hepatocyte intoxication were optimised for allyl alcohol, carbon tetrachloride, D-galactosamine and paracetamol. Silymarin extract, silychristin and silydianin did not exert cytotoxicity (10-100 microM), whereas silybin and isosilybin at higher concentrations and after longer incubation periods were cytotoxic. All main flavonolignans of silymarin tested displayed concentration-dependent cytoprotection against the toxic effects of both allyl alcohol and carbon tetrachloride but neither paracetamol nor galactosamine. The best protection was achieved by silydianin and silychristin and to a lesser degree by silymarin, while silybin and isosilybin were less effective. It is concluded that these differing outcomes result from the varying abilities of the Silybum marianum substances tested to stabilize the cell membrane, exert antioxidant properties and exhibit intrinsic toxicity.
Dvorák
Zdenek
Z
Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacký University Hnevotínská 3, 775 15 Olomouc, Czech Republic.
Kosina
Pavel
P
Walterová
Daniela
D
Simánek
Vilím
V
Bachleda
Petr
P
Ulrichová
Jitka
J
D000082:Acetaminophen / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D001713:Biphenyl Compounds; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005688:Galactosamine / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D010851:Picrates / Q000378:metabolism; D010936:Plant Extracts / Q000633:toxicity; D020005:Propanols / Q000633:toxicity; D014176:Protein Biosynthesis; D014118:Toxins, Biological / Q000633:toxicity*; D020122:tert-Butylhydroperoxide / Q000633:toxicity
D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D001713:Biphenyl Compounds; D005419:Flavonoids; D016166:Free Radical Scavengers; D017705:Lignans; D010851:Picrates; D010936:Plant Extracts; D020005:Propanols; D014118:Toxins, Biological; D000082:Acetaminophen; C006463:allyl alcohol; D005688:Galactosamine; D020122:tert-Butylhydroperoxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D007770:L-Lactate Dehydrogenase