THE EFFECTS OF OSELTAMIVIR (TAMIFLU) ON THE MALE ADULT ALBINO RATS: HISTOLOGICAL, ULTRASTRUCTURAL, BIOCHEMICAL, AND MOLECULAR STUDIES

Abstract

The present work on male adult albino rats investigated the side effects induced by oseltamivir phosphate “tamiflu” which is used as an anti-influenza drug. The testes were the organ of choice, in addition to the blood serum and the leucocytes. In this work, the following studies were carried out: • Histological studies. • Electron microscopical studies • A biochemical study. • Molecular studies. The rats were distributed ─ after weighing each of them ─ to 4 groups (15 rats in each group) that cover the control and the three various applied schemes of oseltamivir. • Group I: Negative control group: The animals of this group were served to get the standard values of the tested parameters. • Group II: The rats were given the therapeutic scheme of oseltamivir, i.e. twice/day for 5 days. This treatment is parallel to the therapeutic scheme applied to humans. • Group III: The rats were given a daily short-term prophylactic scheme of oseltamivir once/day for 10 days. This treatment is parallel to the short-term prophylactic scheme applied to humans. • Group IV: The rats were given the daily long-term prophylactic scheme of oseltamivir once/day for 45 days. This treatment is parallel to the maximum protective scheme applied to humans. Allthe animals of the experimental groups were killed 24 hours after the last dose by severing the neck blood vesselsin concomitant with the control rats for the aimed microscopical, biochemical and molecular analyses.The testes were dissected out and cut into pieces for the histological and transmissionelectronmicroscopical preparations. Other pieces were prepared for DNA gel electrophoresis.Besides, the blood samples were collected for bothbiochemical test and Comet assay. The therapeutic and/or the short-term and long-term prophylacticscheme(s) of “oseltamivir phosphate”converted from human to the rats and calculated according to the table given by Paget and Barnes (1964). The main experimental results are summarized as follows: - Histologically and ultrastructurally, marked deteriorationswere found in the examined testes’ sections of the rats after been orally-administrated with tamiflu. The alterations of the examined seminiferous tubules were highly-recognized in both groups II (the ratsthat were administrated according to the therapeutic scheme) and IV (the rats that were administrated according the long-term prophylactic scheme). In group III – in which the rats were administrated according to the short-term prophylactic scheme – the seminiferous tubules showed few alterations. Microscopically, the most affected cells inside the seminiferous tubules were: Sertoli cells, primary spermatocytes, spermatids, spermatozoa and partially the spermatogonia. The Leydig cells of the interstitial tissue showed marked degeneration, especially in groups II and IV.