Type of Article:  Original Research

Volume 12; Issue 2 (June 2024)

Page No.: 8878-8892

DOI: https://dx.doi.org/10.16965/ijar.2023.276

Comparative Brain Microanatomical and Neurochemical Alterations Following the Administration of Seven Oral Artemisinin-Based Combination Therapies in Swiss Mice

PInnocent A. Edagha 1,2, Promise E. Douglas 1, Aniekan I. Peter 1,3, Aquaisua N. Aquaisua 1, Blessing C. Akpan 4, Edelungudi I. Edagha 5, Moses A. Ataben 1haka *, Peter Gichangi, Adel Abdelmalek, Paul Odula, Julius Ogeng’o.

Faculty of Health Sciences, University of Nairobi, P.O. Box 30197-00100 Nairobi, Kenya.

*1 Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Uyo, Nigeria.

2 Department of Human Anatomy, School of Medicine, Moi University, Eldoret, Kenya.

3 Department of Anatomy, College of Health Sciences, Bowen University, Nigeria.

4 Department of Chemical Pathology, Federal Neuropsychiatric Hospital, Calabar, Nigeria.

5 Department of Family Medicine, Faculty of Clinical Science, University of Uyo Teaching Hospital, Nigeria.


Innocent A. Edagha: 0000-0002-5979-7048

Promise E. Douglas: 0009-0004-6979-2007

Aniekan I. Peter: 0000-0002-1155-6368

Aquaisua N. Aquaisua: 0009-0001-9470-2307

Blessing C. Akpan: 0009-0003-2868-7019

Edelungudi I. Edagha: 0009-0001-4508-3378

Moses A. Ataben: 0000-0001-9312-2362

Corresponding author: Innocent A. Edagha, PhD, Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Uyo, Nigeria. E-Mail: innocentedagha@uniuyo.edu.ng; innocentedagha@mu.ke.a


Over a decade after artemisinin-based combination therapy (ACT) approval as the most preferred anti-malarial drug. Seven ACTs can be sourced as over-the-counter medications in most African pharmacies without prescription. A comparative neurotoxicity of these ACTs was investigated in an in vivo experimental model. Swiss mice numbering 40, weighing 18 – 26 g were allotted to eight groups (n = 5). Group 1 (normal control [NC]), received distilled water 10 mL, while groups 2 to 8 were administered (5.71 mg artesunate+amodiaquine [AA]); (19.29 mg artesunate+mefloquine [AM]); (10.36 mg artesunate+sulfadoxine+pyrimethamine [ASP]); (19.29 mg artesunate+pyronaridine [APy]); (12.5 mg artemisinin+piperaquine [AP]); (15.42 mg dihydroartemisinin+piperaquine [DP]); and (8 mg artemether+lumefantrine [AL]) per kg body weights, respectively orally for 3 days, but for 2 days in group 6.  Animals were sacrificed 24 hrs after last administration under ketamine anaesthesia (100 mg/kg, i.p), and excised brains were evaluated for neurochemical and neurohistological alterations. Oxidative stress markers: malondialdehyde and reduced glutathione significantly (p < 0.05) increased as well as antioxidant enzymes glutathione peroxidase, catalase, superoxide dismutase in ACT-administered groups compared to NC. Neurohistology of hippocampal cornu ammonis 1 (CA1) and cerebellum demonstrated vacuolations, neuronal hypertrophy and atrophy pyramidal, and Purkinje neurons. Immunohistochemistry with glial fibrillary acidic protein antibody demonstrated mild to mostly severe astrogliosis in the ACT-administered groups. In conclusion, oxidative stress markers and antioxidants were elevated in the order DP>APy>AP>ASP>AA>AL>AM. Together with the neurohistology, neurotoxicity were in the order DP>ASP>APy>AP>AL>AA>AM particularly in the hippocampus compared to the cerebellum.

Keywords: Artemisinin-based combination therapies, Cerebellum, CA1 region of the hippocampus, Neurodegeneration, Oxidative stress.


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Cite this article: Innocent A. Edagha, Promise E. Douglas, Aniekan I. Peter, Aquaisua N. Aquaisua, Blessing C. Akpan, Edelungudi I. Edagha, Moses A. Ataben. Comparative Brain Microanatomical and Neurochemical Alterations Following the Administration of Seven Oral Artemisinin-Based Combination Therapies in Swiss Mice. Int J Anat Res 2024;12(2):8878-8892. DOI: 10.16965/ijar.2023.276