Chronic oral exposure to Artemether–lumenfantrine induced testicular and epidydimal damage, germ cell death and severe decrease sperm viability in BALB/c mice

Abstract

Malaria is currently the world's most important parasitic infection, especially in the tropical countries, where the disease has continually been a major cause of morbidity and death. In most African countries, Artemether–lumenfantrine is drug of choice for treatment of malaria and the drug is readily available over the counter, promoting its continuous and indiscriminate use without proper parasitological diagnosis. Here, we investigate the effects of long term but low dose administration of Artemether- lumefantrine on the semen quality and gross weight and histology of the testis and epidydimis of male BALB/c mice. A total of 10 BALB/c male mice weighing 25.2± 0.60g were used and distributed equally into two groups; control and Artemether- lumefantrine. We analyzed absolute and relative testicular weight, and volume, sperm reserve and quality as well as testicular and epidydimal histopathological changes following long term but low dose Artemether- lumefantrine treatment of mice. Both the absolute and relative testicular weights as well as the average testicular volume of treated mice were influenced and significantly decreased. Testicular and epididymal sperm cells storage potential, percentage sperm cells motility and mass activity were significantly decreased in Artemether-lumefantrine treated group compared to control. Also, exposure to Artemether-lumefantrine induced severe disruption of testicular seminiferous tubules with multiple areas of vacuolar degeneration and coagulative necrosis. The epithelia cells of the epidydimis of Artemether-lumefantrine treated mice group also showed severe vacuolar and necrotic degenerations, loss of cilia and multiple foci of lymphocytes infiltrations. In conclusion, this study showed that long term but low dose administration of Artemether-lumefantrine can lead to infertility.