Effects of Artemisinin-Based Combination Therapies on Lipids and Hepatorenal Circulating Indices in Guinea Pigs

Abaram Chesa Mankwe,Jonah Sydney Aprioku,Atuboyedia Wolfe Obianime

doi:10.3844/ajptsp.2016.26.31

Abstract

Artemisinin-based Combination Therapies (ACTs) are employed as first-line agents in malaria chemotherapy. In many malaria endemic areas, ACTs are frequently abused partly due to resistance, poor drug control and inadequate health facilities. This study investigated the effects of prolong administration of Artesunate-Sulfadoxine-Pyrimethamine (ATS-SP), Artesunate-Amodiaquine (ATS-Amod) and Artemether-Lumefantrine (ATM-Lum) on plasma levels of biochemical parameters (AST, ALT, ALP, urea and creatinine) and lipids in guinea pigs. Adult guinea pigs were administered standard (NTD) or Double Therapeutic Dose (DTD) equivalents of ATS-SP, ATS-Amod or ATM-Lum for 14 days. Some other animals received similar drug treatments but were allowed to recover for 14 days. Control group was given vehicle. ATS-Amod caused significant (p<0.05) elevations in AST, ALT, urea and creatinine levels without altering ALP compared to control. The elevations were all reversed except the DTD-induced creatinine elevation. ATS-SP reversibly elevated (p<0.05) AST and creatinine levels. ATM-Lum caused no effect on urea, creatinine and ALT, but increased AST and ALP levels. Lipids were unaffected, except triglyceride level that was reversibly elevated (p<0.05) by ATS-SP (DTD). The results demonstrate that standard doses of the ACTs may have no harmful effects, but prolong overdose treatment with artesunate-amodiaquine or artesunate-SP may elevate creatinine and triglyceride levels, respectively.

Highlights

Malaria is a public health disease which is endemic in the sub Saharan region and it has remained a leading cause of mortality and morbidity in the developing world (Breman et al, 2004)
Normal and double therapeutic dose treatments of artesunate-amodiaquine had no effect on Alkaline Phosphatase (ALP) enzyme plasma level, but caused significant (p
AST and ALT plasma levels were increased by normal and double therapeutic doses of artesunateamodiaquine, whereas it had no effect on ALP

Summary

Introduction

Malaria is a public health disease which is endemic in the sub Saharan region and it has remained a leading cause of mortality and morbidity in the developing world (Breman et al, 2004). Treatment failures have been linked majorly to the development of resistance of the malaria parasite (plasmodium) to standard antimalarial agents (Rønn et al, 1996; Ogutu et al, 2000; Djimdé et al, 2001) This has necessitated the search for new and more effective drugs resulting in the development of artemisinin and its derivatives (artesunate, artelinic acid, artemether, arteether and dihydroartemisinin). Wrong diagnosis of other fever related conditions for malaria (in both clinical and nonclinical settings) is not uncommon and patients are treated repeatedly with antimalarial agents in these areas The consequence of this is overdose and prolong usage of ACTs which raises the concern of drug toxicity (Jaeger et al, 1987)

Methods

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Conclusion