Abstract
We studied ultrastructural changes to clarify the correlation between hepatic damage and membrane effect on erythrocytes of tricyclic antidepressants and bile acid preparation. Chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), chlorimipramine (CIM) and imipramine (IM) were used. The leakage of enzyme from the isolated hepatocyte for hepatic damage and hypotonic hemolysis (50%) was used to evaluate the membrane effect on erythrocyte. CDCA, CIM and IM inhibited the hemolysis at low concentrations and promoted it at high concentration at which hepatic damage occurred were almost the same. In hepatic damage, enzyme leakage was observed from concentrations of 2×10-4 M of CIM and 4×10-4 M of IM and CDCA, with peak leakage at concentrations of 1×10-3 M. There were few changes with UDCA. In SEM, echinocyte or stomatocyte transformation were observed with changes of drug concentrations. Ghost were observed at high 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>IM, CDCA>>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 cristate of the mitochondria, leakage of cytoplasm and lysis of nuclei were observed. These results suggest a good correlation between hepatic damage and erythrocyte membrane lysis by the drugs from the morphological changes.
