A Comparative Study on the Effects of Atenolol, Propranolol and Diltiazem in Mice Hepatocytes

In this study the toxic effect of the three anti hypertensive drugs (atenolol, propranolol and diltiazem) on hepatocytes were investigated.

The 8 weeks old adult male NMRI mice were fed with or without the drugs for 1 month. Mice were divided into 4 groups that received atenolol (50 mg/kg/daily), propranolol (80 mg/kg/daily), and diltiazem (180 mg/kg/daily). Food access was stoped 12 to 15 h before the mice were sacrificed and processed for light and transmission electron microscopic evaluation. In addition modified Hepatitis Activity Index was computed too.

In the control group no pathological sign was observed. Main histological changes such as portal infiltration of lymphocytes and piecemeal necrosis in all three experimental groups as well as expanded necrosis in proparanolol group were seen. In addition electron microscopic imaging indicated an increase in the level of free ribosomes and glycogen droplets in the experimental groups. Also in the mice treated with propranolol group mitochondria membrane disruption were seen, whereas in the group treated with diltiazem, the mitochondrial cristae and endoplasmic reticulum Disintegration could be observed.

Chronic oral administration of atenolol, propranolol and diltiazem in male mice caused hepatotoxicity. The most pathological effects were observed in the group treated with diltiazem, though electrone microscopic imaging indicated the propranolol and dilitiazem were more toxic than the other one.