THE ALTERATIONS OF TESTICULAR TISSUE OF ALBINO MICE DUE TO THE ANTI-ULCER DRUG LANSOPRAZOLE TOXICATION.

Abstract

Abstract Introduction :The anti-ulcer drug lansoprazole with the trade name Zollipak is considered one of the most important and widely used drugs in the Egyptian market for the promotion of healing of ulcers of stomach , duodenum and oesophagus as well as of Zollinger Ellison syndrome due to the hypersecretion of Hcl.Lansoprazole is related to Benzimidazole group of chemical compounds which inhibit the final step of Gastric acid secretion by irreversibility blocking the enzyme system of hydrogen /potassium adenosine triphosphatase , the so called proton pump of gastric parietal cells . Aim of the work :The present investigation was designated to follow, assess and evaluate the side effects due to the use of the therapeutic doses of lansoprazole on albino mice testis from the histological and histomorphometrical points of views . Materials and methods : Fourty adult male mice were equally allocated into 4 groups . Group (i) served as a control group .Group (ii) was daily adiministated with the drug therapeutic dose (0.4mg/kg.body weight ) for 4 weeks .Mice of group (iii) were daily administrated with double the dose (0.8mg/kg.body weight )for 4 weeks . Animals of group (iv)were daily administrated with triple the therapeutic dose (1.2mg/kg.body weight)for the same period . Results and observations :The histopathological results showed that daily treatment with (0.4mg/kg.body weight) Lansoprazole had produced devastations of the spermatogenic cells lining the seminiferous tubules .The seminiferous tubules are detached from each other leaving wider intertubular spaces . The spermatogonia showed shanked and vaculated cytoplasm and nuclear deterioration .The primary spermatocytes were also degenerated and showed obvious shrinkage of their cytoplasm .Their nuclei manifested conspicuous aggregation of the chromatin material . The lumina of the tubules contained debris of damaged spermatids and spermatocytes .The interstitial cells or Leydig cells were decreased in number and the inter-tubular blood vessels were congested . Daily treatment with double the therapeutic doses of lansoprazole (0.8mg/kg.body weight) for 4 weeks had produced severe deteriorative features in the testicular tissues concomitant with disruption of their bounding fibrous capsule or tunica albuginea and severe loss of the connective tissue binding of the seminiferous tubules allowing comparatively wide spaces between them .The spermatogenic cells were decreased in number and displayed conspicuous stoppage of spermatogenesis and marked maturation arrest .The spermatogonia manifested cellular dissolution , vaculated cytoplasm and pyknotic nuclei were commonly observed .Many primary spermatocytes displayed nuclear karyolysis ,necrosis as well as formation of multinucleated giant cells .The interstitial cells were conspicuously deteriorated and became few in number . Treatment with triple the therapeutic dose of lansoprazole (1.2mg/kg.body weight )for 4 weeks had produced vast impairment of mice testicular tissues compared with the previously recorded doses .These changes included severe degeneration of the seminiferous tubules with complete loss of their organization .The spermatogenic cells suffered from necrosis and their nuclei showed pyknosis and karyolysis concomitant with complete stoppage of the process of spermatogenesis up to the spermatid stage as well as aggregation of debris of dead spermatids in the lumina of the deteriorated tubules .The interstitial cells of Leydig were severely damaged and decreased in number .The inter-tubular blood vessels were congested, dilated and showed extravasation of stagnat haemolyzed blood were seen. The histomorphometrical results confirmed the microscopical observations which include significant decrease in number of the seminiferous tubules and the number of interstitial cells .Significant increase in the thickness of the tunica albuginea as well as the number of tubules without sperms as compared with the control group . In conclusion : the previous results indicate that patients treated with such drug doses may take certain precaution during treatment because it could lead to suppression of the process of spermatogenesis , and this will affect the fertility .