Comparative Testicular Histopathological Effects of Artemisinin Derivatives and Some ACTs in the Guinea-pig

Abstract

Artesunate and dihydroartemisinin are artemisinin derivatives, which are effective antimalarial agents used in the treatment of malaria. Combination of artemisinins and other standard antimalarial drugs (ACTs) have resulted in better cure rates of Plasmodium infections. In this study, the histolopathological effects of half, normal and double clinical doses of artesunate, dihydroartemisinin, artesunate/amodiaquine, artesunate/sulfadoxine/pyrimethamine and artemether/lumefantrine on the testes of guinea-pigs were investigated. Mean testicular weight and circumference were both significantly (p<0.05) decreased dosedependently by artesunate/amodiaquine and artemether/lumefantrine, while the other agents decreased only testicular circumference without significant effects on the weight. Furthermore, artesunate and dihydroartemisinin caused dose-dependent distortions of the testicular architecture/histology, characterized by interstitial edema, poor sperm cell differentiation, moderate maturation arrest and impairment of spermatogenesis. The ACTs also caused general inflammation of the testes, with different degrees of edema and depressed sperm production. The clinical dose of artesunate/amodiaquine caused poor differentiation of sperm cells and damage of the seminiferous epithelium. In addition, the half clinical dose of artemether/lumefantrine caused poor development of germ cells, marked maturation arrest and reduced sperm production. There was also marked eosinophilia of the cytoplasm of the spermatocytes, shrinking of the nuclei of the spermatocytes and early signs of necrosis. The results obtained in this study may be due to oxidative damage on the testicular cells/tissues by the antimalarial agents, especially on the Leydig and Sertoli cells of the testis.

Keywords: Artemisinin, ACT, Sertoli, Spermatogenesis, Histopathology