Effect of antihepatotoxic agents against microcystin-LR toxicity in cultured rat hepatocytes.
Primary cultures of adult rat hepatocytes were used to investigate the effects of two putative therapeutic agents, dithioerythritol and silymarin on microcystin-LR-induced hepatotoxicity. Cell injury was assessed by the extent of cellular [14C]adenine nucleotides and lactate dehydrogenase (LDH) release into the medium and the extent of hepatocyte detachment from monolayers. Microcystin-LR (1 microM) induced a significant release of both 14C-labeled nucleotides and LDH from hepatocytes as well as significant detachment of cells from monolayers. Although both dithioerythritol (0.63-5 mM) and silymarin (25-200 microM) reduced the amount of marker release and cell detachment from microcystin-LR-treated wells, silymarin provided significantly greater protection than dithioerythritol at one-tenth the concentration. Furthermore, silymarin and dithioerythritol treatment prevented morphological deformations and detachment of cells.
Mereish
K A
KA
Pathophysiology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701-5011.
Solow
R
R
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000517:prevention & control*; D004226:Dithioerythritol / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000201:enzymology; D008297:Male; D008387:Marine Toxins; D052998:Microcystins; D009711:Nucleotides / Q000032:analysis; D010456:Peptides, Cyclic / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012838:Silymarin / Q000494:pharmacology
D000227:Adenine Nucleotides; D008387:Marine Toxins; D052998:Microcystins; D009711:Nucleotides; D010456:Peptides, Cyclic; D012838:Silymarin; D004226:Dithioerythritol; D007770:L-Lactate Dehydrogenase; C057862:cyanoginosin LR