Efficacy of six artemisinin-based combination therapies in the attenuation of Plasmodium berghei-induced testicular toxicity in Swiss mice

ABSTRACT

Many artemisinin-based combination therapies (ACTs) have been approved for malaria treatment, yet reports indicate that some ACTs pose reversible testicular toxicity; however there is no comparative study of these ACTs on the testes in a curative malarial model. We investigated the ameliorative activity of six ACTs on Plasmodium berghei (PB) induced perturbations in testicular antioxidants, serum testosterone levels, sperm motility and the testes microanatomy. Forty male Swiss mice were divided into 8 groups of 5 each Group 1 normal control (NC), uninfected and untreated, received placebo; group 2 was parasitized non-treated (PNT), while groups 3 - 8 received PB inoculum intraperitoneally. Initial parasitemia was established after 72 hours. Groups 3 - 8 thereafter received oral therapeutic doses of artesunate/amodiaquine (PBAA), artesunate/mefloquine (PBAM), artesunate/sulfadoxine-pyrimethamine (PBASP), artemisinin-piperaquine (PBAP), dihydroartemisinin/piperaquine (PBDP) and artemether/lumefantrine (PBAL) per kg body weight respectively. final parasitemia was performed 24 hours after last treatment, and animals euthanized. Result for parasitemia level was significantly (p < 0.05) declined in ACT-treated groups, except PBASP compared with PNT. Enzymatic antioxidants were significantly (p < 0.0001) altered in ACT-treated groups compared to PNT. Non-enzymatic antioxidants were significantly (p < 0.0001) increased in PBDP compared to NC and PNT. Progressive sperm motility significantly (p < 0.0001) declined in PNT, PBASP, PBAP and PBDP groups compared to NC. Testosterone showed decreasing trend in PBAP compared to PNT, and severe testicular distortions were demonstrated in PNT, PBASP, PBAP and PBDP. This study concludes that therapeutic doses of AA, AM and AL moderately protects against the deleterious effects of Plasmodium berghei-induced testicular toxicity in Swiss mice

RESUMEN

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