Co-exposure to aflatoxin B1 and therapeutic coartem worsens hepatic and renal function through enhanced oxido-inflammatory responses and apoptosis in rats.

Autor: Owumi SE; Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Ibadan, 200004, Nigeria. Electronic address: zicri@hotmail.com., Otunla MT; Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Ibadan, 200004, Nigeria., Elerewe OO; Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Ibadan, 200004, Nigeria., Arunsi UO; Department of Cancer Immunology and Biotechnology, School of Medicine, University of Nottingham, Nottingham, NG7 2RD, UK.
Jazyk: angličtina
Zdroj: Toxicon : official journal of the International Society on Toxinology [Toxicon] 2023 Jan 15; Vol. 222, pp. 106988. Date of Electronic Publication: 2022 Dec 05.
DOI: 10.1016/j.toxicon.2022.106988
Abstrakt: Aflatoxin B1 (AFB 1 ) is a mycotoxin synthesised as a secondary metabolite by members of the Aspergillus species contaminating agricultural produce. Aspergillus species thrive in tropical climes, endemic to malaria. Artemisinin-based combination therapies (ACTs) effectively treat and prevent malaria recrudescence; Coartem (COA) is an ACT whose toxicity is evident. Although there are scanty studies on COA toxicity, the scientific literature is replete on AFB 1 toxic effects -including carcinogenicity. The current research investigates AFB 1 and COA toxicity in experimental Wistar rats' hepatorenal systems. Thirty albino rats were randomly grouped into five cohorts (n = 6) and treated as follows: Group I: Untreated control (2 mL/kg of corn oil); group II: AFB 1 alone (70 μg/kg); group III: COA alone (5 mg/kg); group IV: COA and a low dose of AFB1 1 (5 mg/kg & 35 μg/kg); while Group V: COA and a high dose AFB1 2 (5 mg/kg & 70 μg/kg) by gavage. Our results show that exposure to AFB 1 and COA significantly (p < 0.05) reduced superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities, besides reduced glutathione and total sulfhydryl groups level. Reactive oxygen and nitrogen species, lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, nitric oxide, xanthine oxidase, and myeloperoxidase levels were increased (p < 0.05) in rats co-treated with COA and AFB1. Cell death was aggravated in COA and AFB1 groups, exemplified by increased Caspase-3 and 9 activities and alterations in the typical histological features of experimental rats' livers and kidneys. Finally, rats co-treated with AFB 1 and COA experienced increased hepatorenal dysregulation, oxidative and inflammatory tissue damage, and apoptotic cell death. All the observed systemic perturbations occurred dose-dependently. It is crucial, therefore, to prevent AFB 1 dietary contaminations during COA therapeutic regimen due to increased pathophysiological damage exerted on experimental rat liver and kidneys, as evidenced in this study.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Databáze: MEDLINE
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