Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Plasmodium berghei Malaria in Mice.

Autor:	Samaila A; Department of Human Anatomy, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia.; Department of Pharmacology, College of Health Sciences, Umaru Musa Yar'adua University, Katsina State, Nigeria., Basir R; Department of Human Anatomy, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia., Abdul Aziz NAL; Department of Human Anatomy, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia., Alarabei AA; Department of Human Anatomy, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia., Gambo ML; Department of Microbiology, Faculty of Science, Umaru Musa Yar'adua University, Katsina State, Nigeria., Abdullah MA; Department of Pathology, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia., Hussain MK; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia., Nordin N; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia., Majid RA; Department of Pre-Clinical, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia.
Jazyk:	angličtina
Zdroj:	Iranian journal of parasitology [Iran J Parasitol] 2024 Oct-Dec; Vol. 19 (4), pp. 428-439.
DOI:	10.18502/ijpa.v19i4.17163
Abstrakt:	Background: The interplay of OGG1, 8-Oxoguanine, and oxidative stress triggers the exaggerated release of cytokines during malaria, which worsens the outcome of the disease. We aimed to investigate the involvement of OGG1 in malaria and assess the effect of modulating its activity on the cytokine environment and anemia during P. berghei malaria in mice. Methods: Plasmodium berghei ANKA infection in ICR mice was used as a malaria model. OGG1 concentration and oxidative stress levels in P. berghei -infected mice and their control counterparts were assessed during malaria using enzyme-linked immunosorbent assay. OGG1 activity in malaria mice was modulated using treatment with TH5487 and O8-OGG1 inhibitors. The effects of modulating OGG1 activity using OGG1 inhibitors on cytokine release and anemia during P. berghei malaria infection were assessed by cytometric bead array and measurement of total normal red blood cell count respectively. Results: The plasma OGG1 level was significantly upregulated and positively correlated with parasitemia during P. berghei malaria in mice. Modulation of OGG1 ameliorated malaria severity by improving the total normal RBC count in TH5487 and O8-treated mice. Modulation of OGG1 with TH5487 caused significant reductions in serum levels of TNF-α, IFN-γ, IL-6, and IL-10. Similarly, OGG1 modulation activity using an O8-OGG1 inhibitor caused a significant reduction in serum levels of TNF-α, IL-2, IL-6, and IL-10. Conclusion: The findings indicate the involvement of OGG1 in the P. berghei malaria infection. OGG1 inhibition by TH5487 and O8-OGG1 inhibitors suppressed excessive cytokine release, and this may represent a novel therapeutic strategy for ameliorating the severity of malaria infection. Competing Interests: Conflict of interest Authors declare no conflicts of interest. (© 2024 Samaila et al. Published by Tehran University of Medical Sciences.)
Databáze:	MEDLINE
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