Study on testicular response to prolong artemisinin-based combination therapy treatments in guinea pigs.

Abstract

Artemisinin-based combination therapies (ACTs) are first-line agents in malaria chemotherapy, but often abused in malaria endemic countries including Nigeria. This study investigated the effects of prolong treatment of artesunate-amodiaquine (ATS-Amod), artesunate-sulfadoxine-pyrimethamine (ATS-SP) and artemether-lumefantrine (ATM-Lum) on testicular indices in guinea pigs. Sixty-five pigs were grouped into 13 (n=5 per group). Six groups were given standard or double therapeutic dose equivalents of ATS-Amod, ATS-SP or ATM-Lum daily for 14day and sacrificed 24hr after treatments. Six other groups (recovery groups) received similar drug treatments but allowed to recover for 14day before sacrificed. Control group received distilled water. ATS-Amod, ATS-SP and ATM-Lum, respectively, decreased (p<.01) sperm count (17.7%, 37.7% and 33.8%), motility (48.6%, 50% and 51.4%), viability (32.7%, 43.7% and 35.9%) and morphology (123.5%, 0% and 0%), compared to control. These effects were reversed in recovery animals. Also, they decreased (p<.01) luteinising hormone and testosterone serum levels, without affecting follicle-stimulating hormone. Testicular malondialdehyde level was elevated, and glutathione was decreased, while catalase and superoxide dismutase enzymes were unaffected by the drugs. The alterations were all reversed in recovery animals. The study reveals that prolong administration of ACTs results in reversible alteration of sperm parameters and reduction of testosterone which is partly attributable to oxidative stress.