Modulation of 8-Oxoguanine DNA glycosylase 1 (OGG1) alleviated anaemia severity and excessive cytokines release during Plasmodium berghei malaria in mice

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 en...

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Main Authors: Basir, Rusliza, Abas @ Buang, Razif, Hussain, Mohd Khairi, Nordin, Norshariza, Abdullah, Maizaton Atmadini, Abd Aziz, Nur Aimi Liyana, Abdullahi, Samaila, Gambo, Mukhtar Lawal, Abd Majid, Roslaini
Format: Article
Language:English
Published: Tehran University of Medical Sciences,Danishgah-i Ulum-i Pizishki-i Tihran 2024
Online Access:http://psasir.upm.edu.my/id/eprint/118693/
http://psasir.upm.edu.my/id/eprint/118693/1/118693.pdf
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author Basir, Rusliza
Abas @ Buang, Razif
Hussain, Mohd Khairi
Nordin, Norshariza
Abdullah, Maizaton Atmadini
Abd Aziz, Nur Aimi Liyana
Abdullahi, Samaila
Gambo, Mukhtar Lawal
Abd Majid, Roslaini
author_facet Basir, Rusliza
Abas @ Buang, Razif
Hussain, Mohd Khairi
Nordin, Norshariza
Abdullah, Maizaton Atmadini
Abd Aziz, Nur Aimi Liyana
Abdullahi, Samaila
Gambo, Mukhtar Lawal
Abd Majid, Roslaini
author_sort Basir, Rusliza
building UPM Institutional Repository
collection Online Access
description 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.
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spelling upm-1186932025-07-22T03:43:17Z http://psasir.upm.edu.my/id/eprint/118693/ Modulation of 8-Oxoguanine DNA glycosylase 1 (OGG1) alleviated anaemia severity and excessive cytokines release during Plasmodium berghei malaria in mice Basir, Rusliza Abas @ Buang, Razif Hussain, Mohd Khairi Nordin, Norshariza Abdullah, Maizaton Atmadini Abd Aziz, Nur Aimi Liyana Abdullahi, Samaila Gambo, Mukhtar Lawal Abd Majid, Roslaini 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. Tehran University of Medical Sciences,Danishgah-i Ulum-i Pizishki-i Tihran 2024 Article PeerReviewed text en cc_by_nc_4 http://psasir.upm.edu.my/id/eprint/118693/1/118693.pdf Basir, Rusliza and Abas @ Buang, Razif and Hussain, Mohd Khairi and Nordin, Norshariza and Abdullah, Maizaton Atmadini and Abd Aziz, Nur Aimi Liyana and Abdullahi, Samaila and Gambo, Mukhtar Lawal and Abd Majid, Roslaini (2024) Modulation of 8-Oxoguanine DNA glycosylase 1 (OGG1) alleviated anaemia severity and excessive cytokines release during Plasmodium berghei malaria in mice. Iranian Journal of Parasitology, 19 (4). pp. 428-439. ISSN 1735-7020; eISSN: 2008-238X https://ijpa.tums.ac.ir/index.php/ijpa/article/view/4240 10.18502/ijpa.v19i4.17163
spellingShingle Basir, Rusliza
Abas @ Buang, Razif
Hussain, Mohd Khairi
Nordin, Norshariza
Abdullah, Maizaton Atmadini
Abd Aziz, Nur Aimi Liyana
Abdullahi, Samaila
Gambo, Mukhtar Lawal
Abd Majid, Roslaini
Modulation of 8-Oxoguanine DNA glycosylase 1 (OGG1) alleviated anaemia severity and excessive cytokines release during Plasmodium berghei malaria in mice
title Modulation of 8-Oxoguanine DNA glycosylase 1 (OGG1) alleviated anaemia severity and excessive cytokines release during Plasmodium berghei malaria in mice
title_full Modulation of 8-Oxoguanine DNA glycosylase 1 (OGG1) alleviated anaemia severity and excessive cytokines release during Plasmodium berghei malaria in mice
title_fullStr Modulation of 8-Oxoguanine DNA glycosylase 1 (OGG1) alleviated anaemia severity and excessive cytokines release during Plasmodium berghei malaria in mice
title_full_unstemmed Modulation of 8-Oxoguanine DNA glycosylase 1 (OGG1) alleviated anaemia severity and excessive cytokines release during Plasmodium berghei malaria in mice
title_short Modulation of 8-Oxoguanine DNA glycosylase 1 (OGG1) alleviated anaemia severity and excessive cytokines release during Plasmodium berghei malaria in mice
title_sort modulation of 8-oxoguanine dna glycosylase 1 (ogg1) alleviated anaemia severity and excessive cytokines release during plasmodium berghei malaria in mice
url http://psasir.upm.edu.my/id/eprint/118693/
http://psasir.upm.edu.my/id/eprint/118693/
http://psasir.upm.edu.my/id/eprint/118693/
http://psasir.upm.edu.my/id/eprint/118693/1/118693.pdf