Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia 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 e...
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| Language: | English |
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Tehran University of Medical Sciences
2024-11-01
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| Series: | Iranian Journal of Parasitology |
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| Online Access: | https://ijpa.tums.ac.ir/index.php/ijpa/article/view/4240 |
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| author | Abdullahi Samaila Rusliza Basir Nur Aimi Liyana Abdul Aziz Abdusalam Abdullah Alarabei Mukhtar Lawal Gambo Maizaton Atmadini Abdullah Mohd Khairi Hussain Norshariza Nordin Roslaini Abd Majid |
| author_facet | Abdullahi Samaila Rusliza Basir Nur Aimi Liyana Abdul Aziz Abdusalam Abdullah Alarabei Mukhtar Lawal Gambo Maizaton Atmadini Abdullah Mohd Khairi Hussain Norshariza Nordin Roslaini Abd Majid |
| author_sort | Abdullahi Samaila |
| collection | DOAJ |
| 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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| format | Article |
| id | doaj-art-9b3e6a7daf4d43e0b7fb7002be3b4dde |
| institution | Kabale University |
| issn | 1735-7020 2008-238X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Tehran University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Parasitology |
| spelling | doaj-art-9b3e6a7daf4d43e0b7fb7002be3b4dde2024-12-08T04:38:34ZengTehran University of Medical SciencesIranian Journal of Parasitology1735-70202008-238X2024-11-01194Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Plasmodium berghei Malaria in MiceAbdullahi Samaila0Rusliza Basir1Nur Aimi Liyana Abdul Aziz2Abdusalam Abdullah Alarabei3Mukhtar Lawal Gambo4Maizaton Atmadini Abdullah5Mohd Khairi Hussain6Norshariza Nordin7Roslaini Abd Majid81. Department of Human Anatomy, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, Ma-laysia 2. Department of Pharmacology, College of Health Sciences, Umaru Musa Yar’adua University, Katsina State, NigeriaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, MalaysiaDepartment of Microbiology, Faculty of Science, Umaru Musa Yar’adua University, Katsina State, NigeriaDepartment of Pathology, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, MalaysiaDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, MalaysiaDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, MalaysiaDepartment of Pre-Clinical, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia 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. https://ijpa.tums.ac.ir/index.php/ijpa/article/view/4240MalariaPlasmodium bergheiAnaemiaCytokines |
| spellingShingle | Abdullahi Samaila Rusliza Basir Nur Aimi Liyana Abdul Aziz Abdusalam Abdullah Alarabei Mukhtar Lawal Gambo Maizaton Atmadini Abdullah Mohd Khairi Hussain Norshariza Nordin Roslaini Abd Majid Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Plasmodium berghei Malaria in Mice Iranian Journal of Parasitology Malaria Plasmodium berghei Anaemia Cytokines |
| title | Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Plasmodium berghei Malaria in Mice |
| title_full | Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Plasmodium berghei Malaria in Mice |
| title_fullStr | Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Plasmodium berghei Malaria in Mice |
| title_full_unstemmed | Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Plasmodium berghei Malaria in Mice |
| title_short | Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Plasmodium berghei Malaria in Mice |
| title_sort | modulation of 8 oxoguanine dna glycosylase 1 ogg1 alleviated anemia severity and excessive cytokines release during plasmodium berghei malaria in mice |
| topic | Malaria Plasmodium berghei Anaemia Cytokines |
| url | https://ijpa.tums.ac.ir/index.php/ijpa/article/view/4240 |
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