Dose and time-dependent effect of orange juice on the antimalarial efficacy of artemether-lumefantrine, haematological, and antioxidant parameters

John K. Iregbu; Jessica C. Iregbu; Gabriel C. Edeh; Daniel L. Ajaghaku; Christian C. Nwoye; Ezinneamaka M. Ashibogwu; Chukwuemeka C. Njoku; Chidera M. Ugwuegbu; Bostock C. Okafor; Obinna H. Tony-Okpalaobi; Chibuikem E. Okparaeke

doi:10.18203/2320-6012.ijrms20252772

Authors

John K. Iregbu Department of Medicine and Surgery, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria https://orcid.org/0009-0008-6335-8209
Jessica C. Iregbu Department of Pharmacy, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria
Gabriel C. Edeh Department of Haematology, Babcock University Teaching Hospital, Ilishan-Remo, Ogun State, Nigeria https://orcid.org/0000-0002-2212-7083
Daniel L. Ajaghaku Department of Pharmacology, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Enugu State, Nigeria
Christian C. Nwoye Department of Medicine and Surgery, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria https://orcid.org/0009-0006-7471-7794
Ezinneamaka M. Ashibogwu Department of Medicine and Surgery, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria https://orcid.org/0009-0004-4796-5552
Chukwuemeka C. Njoku Department of Obstetrics and Gynaecology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria https://orcid.org/0009-0008-1772-2321
Chidera M. Ugwuegbu Department of Surgery, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria
Bostock C. Okafor Department of Medicine and Surgery, College of Health Sciences, University of Abuja, Federal Capital Territory, Nigeria https://orcid.org/0009-0009-3612-9416
Obinna H. Tony-Okpalaobi Department of Internal Medicine, Federal Medical Centre, Jabi, Abuja, Nigeria
Chibuikem E. Okparaeke Department of Medicine and Surgery, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria

DOI:

https://doi.org/10.18203/2320-6012.ijrms20252772

Keywords:

Ascorbic acid, Malaria, Arthemether/lumefantrine, Dose and time dependent effects, Orange juice, Anti-malarial

Abstract

Background: Orange juice (OJ) contains ascorbic acid, which has antioxidant properties that would be expected to protect against haemolytic effects and possibly interfere with the antimalarial mechanism of the artemisinin-based combination therapy. This study was designed to investigate the dose and time-dependent effect of OJ on the anti-malarial efficacy of artemether-lumefantrine (AL).

Methods: Malaria was induced by inoculating plasmodium berghei parasite through the intraperitoneal route to albino mice. The infection was allowed to establish for 3 days, followed by treatment with AL alone, and its combination with graded doses of OJ. Separate doses of OJ were also administered to different groups.

Results: Treatment with AL alone produced total parasite clearance (100%) in days 3 and 4 post-treatment. Co-administration of AL with graded doses of OJ showed significant (p<0.05) increase in parasitemia at OJ combination doses of 10, 8, and 6 ml/kg. Unlike antagonistic combination interaction exhibited by higher combination doses of OJ, lower combination doses of 4 and 2 ml/kg potentiated the antiplasmodial activity of AL. Compared to vehicle (malaria) control group, a significant (p<0.05) increase in PCV was achieved at combination OJ doses of 10, 8, 6, and 4 ml/kg. Combination doses of OJ at 10, 8, 6 ml/kg restored the catalase enzyme activity to the level that exist in uninfected naïve control group.

Conclusions: OJ showed both antagonistic and beneficial interactions with AL at higher and lower doses, respectively. Combination of OJ with AL also has a beneficial effect in reducing both parasite and AL-induced oxidative stress.

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