Summary
The influence of acrolein on hepatocytes and the effect of a-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 μM 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 μM acrolein and 20 μM α-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 cotreatment with a-tocopherol. Ultrastructural alterations of hepatocytes induced by acrolein were minimized by co-treatment with α-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 α-tocopherol can prevent the hepatocellular injury, even under condition of lack of GSH and GSH-Px.
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Watanabe, M., Sugimoto, M. & Ito, K. The acrolein cytotoxicity and cytoprotective action of α-tocopherol. Gastroenterol Jpn 27, 199–205 (1992). https://doi.org/10.1007/BF02777723
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DOI: https://doi.org/10.1007/BF02777723