Mechanism of maintenance of liver-specific functions by DMSO in cultured rat hepatocytes.
The present study was undertaken to investigate the mechanism by which dimethylsulfoxide (DMSO) exerts its protective action on cytochrome P450-dependent activities and differentiation in cultured rat hepatocytes. Loss of cytochrome P450 is associated with a shortage of heme and reduced activity of delta-aminolaevulinic acid dehydratase: the addition of DMSO, which induces this enzyme in human hepatoma cells, is not able to affect it in hepatocytes in primary culture. DMSO is a strong scavenger of hydroxyl radicals and may destroy the reactive oxygen species formed under conventional culture conditions (i.e., 95% air and 5% CO2). In fact other powerful scavengers of oxygen radicals like dimethylthiourea, desferal, and catalase itself maintain higher levels of cytochrome P450 and higher activities of 7-ethoxycoumarin O-deethylase during 3 days of culture. DMSO and the other scavengers are also able to retain features of the morphological and biochemical differentiation of hepatocytes such as the ability to induce tyrosine aminotransferase activity in response to glucocorticoids.
Villa
P
P
C.N.R. Center of Cytopharmacology, Department of Pharmacology, Milan, Italy.
Arioli
P
P
Guaitani
A
A
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D016166:Free Radical Scavengers; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats
D016166:Free Radical Scavengers; D003577:Cytochrome P-450 Enzyme System; D015660:7-Alkoxycoumarin O-Dealkylase; D004121:Dimethyl Sulfoxide