Effect of various drugs on cell membrane.

Abstract

We studied ultrastructural changes to clarify the correlation between hepatic damage and membrane effect on erythrocytes of tricyclic antidepressants and bile acid preparations. Cheno-deoxycholic acid(CDCA), ursodeoxycholic acid(UDCA), chlor-imipramine(CIM) and Imipramine(IM) were used. The leakage of enzyme from the isolated hepatocytes for hepatic damage and hypotonic hemolysis(50%) was used to evaluate the membrane effect on erythrocytes. CDCA, CIM and IM inhibited the hemolysis at low concentrations and promoted it at high concentrations. The concentration at which hemolysis started and the concentration at which hepatic damage occurred were almost the same. In SEM, crenation or cup transformation and increase in ghosts were observed with increasing drug concentration. At concentrations where hemolysis was inhibited, these changes were mild and the morphology resembled that of discocytes. The sequence of the severity was CIM>CDCA>IM>UDCA. Deformation of hepatocytes became more severe as the concentrations of CIM and CDCA increased. Appearance of many spherical protrusions on the cell membrane was observed. In TEM, there were marked disappearance of microvilli, destruction of the cell, and the cell membrane became vesicular. Disappearance of the cristae of the mitochondria, leakage of cytoplasma and lysis of nuclei were observed. These results suggest a good correlation between hepatic damage and erythrocyte membrane lysis by the drugs.