The acrolein cytotoxicity and cytoprotective action of alpha-tocopherol in primary cultured rat hepatocytes.
The influence of acrolein on hepatocytes and the effect of alpha-tocopherol on acrolein cytotoxicity were investigated using primary cultured rat hepatocytes. Hepatocellular injury was dependent on both acrolein concentration in medium and on duration of exposure. Treatment of hepatocytes with 100 microM acrolein resulted in a marked loss of cellular glutathione (GSH) within 15 min, gradual accumulation of cellular lipid peroxide (LPO) and subsequent lactate dehydrogenase (LDH) leakage in the medium from 3 hr after exposure to acrolein. Cellular GSH peroxidase (GSH-Px) activity at 2 hr was significantly decreased. Electron microscopic examination on hepatocytes at 8 hr revealed a marked swelling of mitochondria and ruptures of the plasma membrane. Simultaneous treatment with 100 microM acrolein and 20 microM alpha-tocopherol did not prevent the loss of cellular GSH, though it prevented the LPO accumulation and the LDH leakage. The decrease of cellular GSH-Px activity with acrolein treatment was not mitigated by co-treatment with alpha-tocopherol. Ultrastructural alterations of hepatocytes induced by acrolein were minimized by co-treatment with alpha-tocopherol. In conclusion, acute loss of GSH and GSH-Px may increase cellular LPO and lead to hepatocellular injury, though suppression of cellular LPO accumulation by alpha-tocopherol can prevent the hepatocellular injury, even under condition of lack of GSH and GSH-Px.
Watanabe
M
M
Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Sugimoto
M
M
Ito
K
K
D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects; D008933:Mitochondrial Swelling / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology*
D008054:Lipid Peroxides; D014810:Vitamin E; D000171:Acrolein; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D005978:Glutathione