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Abstract
Dose and treatment-duration neurotoxic effects are reported for artemisinin drugs of mostly the liposoluble derivatives; and yet artemether, the only parenteral formulation of the artemisinin series available in Nigeria is fat-soluble and also has a treatment-duration of 5–7 days (in an attempt to delay recrudescence). Since parenteral drugs are usually resorted to in severe/complicated or multidrug-resistant malaria against the oral artemisinin co-formulated therapies (ACT), this study is aimed to investigate the pathological changes on selected tissues (if any), in rats, of the normal 7-days artemether-injections when used both in the normal and higher doses. Artemether was administered i.p., at three dose levels, equivalent to therapeutic dose (1.5 mg kg−1) as well as 5 and 10 times higher (7.5 and 15 mg kg−1). A three percentage v/v Tween 80 vehicle was used for the control experiment. The pathological changes in the kidney, heart, liver, and lungs evaluated using percentage mean organ:body-weight ratio showed no changes in the organs. No histopathological effect was observed in the organs of rats treated with 1.5 mg kg−1. However, rats treated with 7.5 and 15 mg kg−1 revealed necrositic lesions with mononuclear cellular-infiltration in the liver and brain. The liver had focal area necrosis, while the brain had liquefactive necrosis, neuronal degeneration, congested blood vessels, hemorrhage, and vacuolations. The interstitial spaces of the glomerulus and renal tubules of one kidney from rats that received 15 mg kg−1 had focal area fibrositic-necrosis.
Acknowledgments
The authors are grateful for the technical assistance provided by Mr Charles Ebute and Mr John Kono who are in charge of the department laboratory where this work was carried out.