SERUM AND LIVER ALKALINE PHOSPHATASE IN ETHINYLESTRADIOL-INDUCED CHOLESTASIS (A PARALLEL BIOCHEMICAL AND MORPHOLOGICAL STUDY)

Abstract

The purpose of this paper was to investigate the effect of higher estrogenizing EE doses on serum APase and to compare these results with the histochemical and ultrastructural assessment of the enzyme in the liver under the same conditions. We induced cholestasis with EE in doses of3 and 6 mg/kg b. m. in 93 female rats. The effect of EE on the activity of both serum and tissue APase on the 24th hour as well as after a 3, 5, and 7-day-long treatment was analyzed. The influence of EE on the hepatic Apase activity was semiquantitative^ read (-, + +, ++, +++) on tissue sections after demonstration accorrding to Gomori's method and ultrastructurally, after identification according to the method of Hugon and Borgers. There was an enhancement of both serum and hepatic APase activity by 100 per cent established already on the 24th hour when EE in a dosis of 6 mg/kg b.m. was applied but hardly after the third day when EE in a dosis of 3 mg/kg b. m. was administered. The maximal effect of increasing enzyme activity in the superficial hepatocytic membranes was achieved on the third day with the dosis of 6 mg/kg b. m. but on the fifth day with the dosis of 3 mg/kg b. Ñ‚.; in the serum, these time intervals were 7 and 3 days, respectively. There were great differences concerning the intensity and distribution in the hepatic lobulus - from a completely absent enzyme induction to a disseminated enzyme reaction in all the areas of the hepatic lobules. Electron microscopically, a progressive damage of the canalicular villi manifested by a vacuolization, reduction and even loss of APase activity as well as by an appearance of enzyme reaction in the lateral and sinusoidal membranes of hepatocytes was observed. APase secretion through the lateral and sinusoidal membranes of hepatocytes could explain the increased enzyme values in the serum.Our investigation demonstrated that higher estrogenizing doses caused a rapider and more intensive enzyme induction in the hepatocytic membranes in 80-100 per cent of the animals. Serum enzyme elevation was detected in all the animals which was probably due to the enhancement of the osseous isoenzyme, too.