THE PATHOGENIC EFFECTS OF THE ANT-ULCER DRUG “LANSOPRAZOLE” (ZOLLIPAK) ON THE LIVER OF ALBINO MICE

Abstract

ABSTRACT The anti-ulcer drugs are useful agents for eradication of many cases of peptic ulcers, erosive oesophigitis, Zollinger Elison syndromes as well as gastric erosions. These drugs decrease the gastric parietal cells acid secretion by inhibiting H(+), K(+) adenosine triphosphatase, the final step in the secretion of HCl. The present investigation was designated to evaluate the effects of one of these drugs namely “Lansoprazole” with the trade name “Zollipak” on the liver of albino mice from the histological and ultrastructural points of view. Fourty adult male albino mice were used in the present investigation. They were equally allocated into 4 groups. Mico of the first group were considered as a control group. Animals of the second group was given daily the therapeutic oral dose of “lansoprazole” i.e. 0.4 mg/kg body weight for 4 weeks. The third group was treated daily with double the therapeutic dose of the drug, i.e. 0.8 mg/kg body weight for 4 weeks. The fourth group was administered daily with triple the therapeutic dose, i.e. 1.2 mg/kg body weight for the same period. The histopathological findings showed mild devastation of the hepatic parenchyma of mice treated with 0.4 mg/kg body weight “lansoprazole”, being in the form of cloudy swelling of the hepatocytes cytoplasm, nuclear pyknosis and karyorrhexis. The central veins and the surrounding sinusoids were congested and dilated. Nonetheless, in the case of daily treatment with double the therapeutic doses of “lansoprazole” i.e. 0.8 mg/kg body weight the hepatic tissues manifested hydropic degeneration and conspicuous nuclear karyolysis, concomitant with such effects the blood vasculatures were severely congested, dilated and filled with stagnant haemolyzed blood; markedly activated phagocytic Kupffer cells were seen pushed into the lumine of the hepatic sinusoids. Severe consequences were recorded in the fourth group treated with 1.2 mg/kg body weight of “lansoprazole” where the hepatocytes illustrated marked vacuolar degeneration in some areas, coagulative necrosis in other areas and focal inflammatory cellular infiltration besides obvious nuclear karyolysis. The central veins and the sinusoids were severely deteriorated, damaged and showed erosion of their endothelial linning cells. The ultrastructure results manifestesd obvious consequences in the case of daily treatment with 0.4 mg/kg body weight of “lansoprazole”. The hepatocytes displayed obvious mitochondrial swelling which showed rather condensed matrices. The rough endoplasmic reticulum was proloiferated and lost its attachment with the nucleus. Also, the surrounding cytoplasm was vacuolated. The nuclei illustrated homogenous distribution of their chromatin. In the case of daily treatment with 0.8 mg/kg body weight of “lansoprazole” for 4 weeks the mitochondria were severely devastated; they lost their internal matrices and ridges and showed ruptured membranes. The rough endoplasmic reticulum was fragmented into smaller stacks and degranulated. The nuclei showed margination of their heterochromatin on their nuclear envelopes. However, in case of daily treatment with 1.2 mg/kg body weight of “lansoprazole” for 4 weeks, the hepatocytes mitochondria were deteriorated as they appeared as empty vacuoles. Besides, obvious fragmentation of the cisternae of RER as well as conspicuous hyperplasia of the stacks of smooth endoplasmic reticulum (SER) was shown. The nuclei displayed obvious chromatinolysis. The hepatic sinusoids were devastated, dilated, congested and filled with stagnant haemolyzed blood.