Effects of Six Artemisinin-Based Combination Therapies On Blood Glucose, Pancreatic Histology and Insulin Immunolocalization: An Experimental Malaria Study

Acute pancreatitis has been reported during and after malaria treatment. This study characterized the effects of six artemisinin-based combination therapies (ACTs) on the blood glucose, pancreas histology and insulin immunolocalization in a curative malaria model. Forty male Swiss adult mice were divided into 8 groups of 5 animals each. Murine malaria was induced in groups 2 – 8 via intraperitoneal injection of 0.2 ml containing 1 x 106Plasmodium berghei ANKA parasites. Groups 1 and 2 representing negative and positive controls (NC and PC), received 5 ml/kg distilled water only, groups 3 to 8 received oral therapeutic doses of 5.7 mg of artesunate-amodiaquine (AA), 6.43 mg artesunate-mefloquine (AM), 25.36 mg artesunate-sulfadoxine-pyramethamine (ASP), 12.5 mg artemisininpiperaquine (AP), 5.14 mg dihydroartemisinin–piperaquine (DP) and 8 mg arthemeter-lumefantrine (AL) respectively standard regimen of 2-3 days, and 24 hours after the last treatment, animals were sacrificed under chloroform inhalation. The pancreases were carefully harvested, rinsed in normal saline and fixed in 10 % buffered formalin for tissue processing. Final parasitemia, blood glucose levels, pancreas histology and insulin immunolocalization were determinedby standard protocols. Results showed all the ACTs were effective against hyperparasitemia except ASP, and AM appeared the most effective. Blood glucose was not significantly altered, and this correlated with strong insulin expression across all groups, there was mild edema and inflammation in the test groups compared to NC. In conclusion murine malaria and hyperparasitemia clearance with the six ACT may cause acute pancreatitis but does not alter blood glucose levels, and strongly demonstrated insulin expression.

Key Words: Malaria, Artemisinin-based combination therapies, ancreas, Insulin, Blood glucose