Investigating the Comparative Effects of Six Artemisinin-based Combination Therapies on Plasmodium-induced Hepatorenal Toxicity.

Background: Too many artemisinin-based combination therapies (ACTs) are available, thus creating a dilemma on the most preferred for the treatment of malaria.

Aim: We compared the effect of six ACTs in mitigating Plasmodium-induced hepatorenal toxicity in experimental malaria.

Materials and methods: Forty adult male Swiss mice allotted into eight groups: Group 1 (normal control [NC] uninfected and untreated), Group 2 (parasitized nontreated - [PNT]), and Groups 3-8 received Plasmodium berghei inoculum. After 72 h, the initial parasitemia was established. Groups 3-8 were administered oral therapeutic doses of artesunate-amodiaquine (AA), artesunate-mefloquine (AM), artesunate-sulfadoxine-pyrimethamine (ASP), artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL) per kg bodyweight, respectively, as standard regimen, and final parasitemia determined. Animals were euthanized via chloroform inhalation and blood collected for hepatorenal analysis. Liver and kidney were dissected out for histology.

Results: Parasitemia was significantly (P < 0.05) decreased in tests compared to PNT, except in ASP group. Liver enzymes were significantly (P < 0.05) increased in PNT compared to tests and NC. Hyperplastic cells and portal tract inflammation were prominent in ASP group, but mild to moderate in other treated groups. Urea-creatinine were significantly (P < 0.05) increased in PNT compared to treated groups. The Na⁺ and Cl^- were significantly (P < 0.05) reduced in PNT, with significantly (P < 0.05) increased K⁺ compared to NC and treated groups. Glomerulonephritis and glomerulus splitting was observed in PNT, while moderate distortions were observed in treated groups. The AA and AM groups had good kidney histoarchitecture.

Conclusion: Parasitemia decreased in all the treatment groups except in PNT and ASP groups which had severe hepatorenal distortions. Hepatorenal histoarchitecture were mildly distorted in the AA, AM and AL-administered groups with lower hepatorenal indices comparable to NC. The least elevated liver enzymes were in AA and AM. In decreasing order ASP > DP > AL > AP > AM > AA.