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Fulltext Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum

Ibraheem ZO, Abd Majid R, Noor SM, Sedik HM, Basir R

Malar Res Treat, 2014;2014:950424.
PMID: 25506039 DOI: 10.1155/2014/950424

Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs.
Evaluation of Bactimos wettable powder, granules and briquets against mosquito larvae in Malaysia

Sulaiman S, Jeffery J, Sohadi AR, Yunus H, Busparani V, Majid R

Acta Trop, 1990 May;47(4):189-95.
PMID: 1973019

There was high mortality in late larval instars of Aedes albopictus (Skuse) from laboratory and field populations in the 24 h after application of three Bactimos formulations of Bacillus thuringiensis H-14. Mortalities were higher and residual effects longer in field populations than in laboratory ones. Briquets were the most effective formulation (mortality 96-100% after five weeks; 76-92% after eight weeks). Culex quinquefasciatus Say larvae were tested only against the briquet formulation. In the laboratory, 100% mortality of late instars persisted for six weeks and dropped to 48-88% after eight weeks. In the field, late instars were reduced by 62-87% after 24 h and 69-72% after one week compared to increases in an untreated population of 160% and 176% respectively.
The Potential of β Carbolin Alkaloids to Hinder Growth and Reverse Chloroquine Resistance in Plasmodium falciparum

Ibraheem ZO, Abdul Majid R, Mohd Noor S, Mohd Sidek H, Basir R

Iran J Parasitol, 2015 Oct-Dec;10(4):577-83.
PMID: 26811724

Nowadays, scourge of malaria as a fatalistic disease has increased due to emergence of drug resistance and tolerance among different strains of Plasmodium falciparum. Emergence of chloroquine (CQ) resistance has worsened the calamity as CQ is still considered the most efficient, safe and cost effective drug among other antimalarials. This urged the scientists to search for other alternatives or sensitizers that may be able to augment CQ action and reverse its resistance.
Fulltext Andrographolide effect on both Plasmodium falciparum infected and non infected RBCs membranes

Zaid OI, Abd Majid R, Sabariah MN, Hasidah MS, Al-Zihiry K, Yam MF, et al.

Asian Pac J Trop Med, 2015 Jul;8(7):507-12.
PMID: 26276279 DOI: 10.1016/j.apjtm.2015.06.007

OBJECTIVE: To explore whether its antiplasmodium effect of andrographolide is attributed to its plausible effect on the plasma membrane of both Plasmodium falciparum infected and non-infected RBCs.
METHODS: Anti-plasmodium effect of andrographolide against Plasmodium falciparum strains was screened using the conventional malaria drug sensitivity assay. The drug was incubated with uninfected RBCs to monitor its effect on their morphology, integrity and osmotic fragility. It was incubated with the plasmodium infected RBCs to monitor its effect on the parasite induced permeation pathways. Its effect on the potential of merozoites to invade new RBCs was tested using merozoite invasion assay.
RESULTS: It showed that at andrographolide was innocuous to RBCs at concentrations approach its therapeutic level against plasmodia. Nevertheless, this inertness was dwindled at higher concentrations.
CONCLUSIONS: In spite of its success to inhibit plasmodium induced permeation pathway and the potential of merozoites to invade new RBCs, its anti-plasmodium effect can't be attributed to these functions as they were attained at concentrations higher than what is required to eradicate the parasite. Consequently, other mechanisms may be associated with its claimed actions.
Fulltext The prevalence of Enterobius vermicularis amongst primary school children in Pulau Ketam, Selangor--1988

Oothuman P, Rampal L, Omar B, Marwsi MA, Mohammod CG, Jeffery J, et al.

Med J Malaysia, 1989 Dec;44(4):312-6.
PMID: 2520040

A survey was conducted to investigate the prevalence of Enterobius vermicularis in 1352 Chinese children between the ages of 6-12 years from the three National Type Chinese Primary Schools in Pulau Ketam in 1988, using the scotch-tape technique on three successive days. The overall prevalence was high (56.88%). The prevalence in Sin Bin School was significantly lower (50.86%) compared to the other two schools (56.60% and 61.04%). Prevalence was significantly higher amongst the 6-7 years age group (61.61%-70.18%) compared to other age groups (47.9%-59.29%). There was no difference in the prevalence between the boys and girls being 56.15% and 57.55% respectively.
Fulltext Anti-plasmodial and Chloroquine Resistance Suppressive Effects of Embelin

Zaid OI, Majid RA, Hasidah MS, Sabariah MN, Al-Zihiry K, Rahi S, et al.

Pharmacogn Mag, 2017 Jan;13(Suppl 1):S48-S55.
PMID: 28479726 DOI: 10.4103/0973-1296.203982

BACKGROUND: Emergence of chloroquine (CQ) resistance among different strains of Plasmodium falciparum is the worst catastrophe that has ever perplexed the dedicated efforts to eradicate malaria. This urged the scientists to search for new alternatives or sensitizers to augment its antiplasmodium effect.
MATERIALS AND METHOD: In this experiment, the potential of embelin, isolated from Embelia ribes, to inhibit the growth and sensitize CQ action was screened using SYBRE-green-I based drug sensitivity and isobologram assays, respectively. Its effect on red blood cells stability was screened to assess its safety. To explore its molecular mechanism, its effect on plasmodial Hemozoin and the in vitro β-hematin formation was screened as well. Furthermore, its anti-oxidant activity was measured using the conventional in vitro tests and its molecular characters were obtained using Molispiration program.
RESULTS: The results showed that its anti-plasmodial effect was weaker than CQ but synergism was obtained when they were combined at ratios lower than 5:5 CQ/embelin. Furthermore, β-hematin formation was inhibited by embelin without showing any synergism after mixing with CQ.
CONCLUSION: Overall, embelin is not ideal to be suggested as a conventional antiplasmodium but it has a potential to ameliorate CQ resistance. Furthermore, its action is not related to its impact on hemozoin formation. Further, investigations are recommended to illustrate its detailed mechanism of action. Abbreviation used: CQ-DV-PBS-HEPES: Chloroquine-Digestive vacuole-Phosphate-buffer-saline-4-(2-hydroxyethyl-1-piperazin-ethan-sulphoni-acid), EDTA: Ethylen-diamin-tetra-acetic-acid, g.m.wt: Gram molecular weight, cMCM: Complete-malaria-culture-medium, Hct: Hematocrite, PRBCs: Parasitized-redblood-cells, nRBCs: Normal-red-blood-cells, RT: Room temperature, IC: Inhibitory concentration, FIC: Fractional inhibitory concentration, iCM: Incomplete-culturemedium, BSA: Bovin serum albumin, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DPPH: 2,2-diphenyl-1- picrylhydrazy, BHT: Butylatedhydroxyl-toleuen, PSA: Polar surface area, ClogP: Log partition coefficient (octanol/water), GPCR: G-protein-coupled-receptors, DMSO: Dimethylsulphoxide, NaOH: Sodium hydroxide.
Investigations for the Possible Use of a Monoclonal Antibody Produced against Strongyloides ratti Antigen as an Immunodiagnostic Reagent for Active Strongyloidiasis

Mahmuda A, Bande F, Abdulhaleem N, Abd Majid R, Awang Hamat R, Omar Abdullah W, et al.

Iran J Parasitol, 2018 8 3;13(2):204-214.
PMID: 30069204

Background: Currently, most of the available serological diagnostic kits for strongyloidiasis are based on the use of the crude antigens of Strongyloides ratti, which are good, but with less sensitivity towards the infection. Hence, this study aimed to produce and evaluate monoclonal antibody for detecting soluble parasite antigen in animal sera.
Methods: The study was conducted in the Department of Medical Microbiology and Parasitology, University Putra Malaysia in 2014-2017. Saline extract protein from the infective larvae of S. ratti was used to immunize BALB/c mice and subsequent fusion of the B-cells with myeloma cells (SP2/0) using 50% PEG. The hybridomas were cultured in HAT medium and cloned by limiting dilutions. Positive hybrids were screened by indirect ELISA. The ascites fluid from the antibody-secreting hybridoma was purified and the MAb was characterized by western-blots and evaluated in sandwich ELISA for reactivity against the homologous and heterologous antigens.
Results: An IgG1 that recognizes a 30 and 34 kDa protein bands was obtained. The MAb was recognized by all S. ratti-related antigens and cross-reacted with only Toxocara canis antigens in both assays. The minimum antigen detection limit was found to be 5 ng/ml. All antibody-positive rat and dog sera evaluated have shown antigen-positive reactions in Sandwich-ELISA.
Conclusion: The MAb produced, was able to detect antigens in strongyloidiasis and toxocariasis in animal models and may also be useful for the serological detection of active strongyloidiasis and visceral toxocariasis in human sera.
Fulltext Critical Roles of IL-33/ST2 Pathway in Neurological Disorders

Abd Rachman Isnadi MF, Chin VK, Abd Majid R, Lee TY, Atmadini Abdullah M, Bello Omenesa R, et al.

Mediators Inflamm, 2018;2018:5346413.
PMID: 29507527 DOI: 10.1155/2018/5346413

Interleukin-33 (IL-33) is an IL-1 family member, which exhibits both pro- and anti-inflammatory properties solely based on the type of the disease itself. Generally, IL-33 is expressed by both endothelial and epithelial cells and mediates its function based on the interaction with various receptors, mainly with ST2 variants. IL-33 is a potent inducer for the Th2 immune response which includes defence mechanism in brain diseases. Thus, in this paper, we review the biological features of IL-33 and the critical roles of IL-33/ST2 pathway in selected neurological disorders including Alzheimer's disease, multiple sclerosis, and malaria infection to discuss the involvement of IL-33/ST2 pathway during these brain diseases and its potential as future immunotherapeutic agents or for intervention purposes.
Progression of malaria induced pathogenicity during chloroquine therapy

Zaid OI, Abd Majid R, Sidek HM, Noor SM, Abd Rachman-Isnadi MF, Bello RO, et al.

Trop Biomed, 2020 Mar 01;37(1):29-49.
PMID: 33612716

Treatment Failure with chloroquine is one of the challenges that faced the dedicated efforts to eradicate malaria This study aims at investigating the impact of treatment failure with chloroquine on the progression of the disease-induced histo-pathogenic and immunogenic outcomes. To achieve this, Rane's protocol with modifications was applied on a model of Plasmodium berghei ANKA infected ICR mice to determine the dose response curve of chloroquine and to screen the treatment impact on the disease progression. Chloroquine was given at 1, 5, 10, 15 and 20 mg/kg once the parasitemia reached to 20-30% (the experimental initiation point). During the subsequent days, the mice were monitored for changes in the clinical signs, hematology parameters and the progress of the parasitemia until the parasitemia reached to 60-70% (the experimental termination point) or up to 10 days after chloroquine administration in case of achieving a complete eradication of the parasite. At the end, the mice were exsanguinated and their blood and organs were collected for the biochemistry and the histology study. A complete eradication of the parasite was achieved at 20 mg/kg while recrudescence was observed at the lower doses. At 1 mg/kg, the parasite growth was comparable to that of the positive control. The histo-pathogenic and immunogenic changes were stronger in the groups that experienced recrudescence (at 5 and 10 mg/kg). All in all, the study highlights the possibility of having a worsened clinical condition when chloroquine is given at its sub-therapeutic doses during malaria treatment.
Fulltext Molecular Detection and Genetic Diversity of Toxoplasma gondii Oocysts in Cat Faeces from Klang Valley, Malaysia, Using B1 and REP Genes in 2018

Nasiru Wana M, Mohd Moklas MA, Watanabe M, Zasmy Unyah N, Alhassan Abdullahi S, Ahmad Issa Alapid A, et al.

Pathogens, 2020 Jul 16;9(7).
PMID: 32708648 DOI: 10.3390/pathogens9070576

The major route for Toxoplasma gondii (T. gondii) infection is through the ingestion of foods contaminated with oocyst from cat faeces. The microscopic detection of T. gondii oocysts in cat faeces is challenging, which contributes to the failure of detecting or differentiating it from other related coccidian parasites. This study aims to detect T. gondii oocysts in cat faeces using two multicopy-target PCR assays and to evaluate their genetic diversity. Cat faecal (200) samples were collected from pet cats (PCs; 100) and free-roaming cats (FRCs; 100) within Klang Valley, Malaysia, and screened for coccidian oocysts by microscopy using Sheather's sucrose floatation. PCR assays were performed on each faecal sample, targeting a B1 gene and a repetitive element (REP) gene to confirm T. gondii oocysts. Additionally, the PCR amplicons from the REP gene were sequenced to further confirm T. gondii-positive samples for phylogenetic analysis. Microscopy detected 7/200 (3.5%) T. gondii-like oocysts, while both the B1 gene and the REP gene detected 17/200 (8.5%) samples positive for T. gondii. All samples that were microscopically positive for T. gondii-like oocysts were also shown to be positive by both B1 and REP genes. The BLAST results sequenced for 16/200 (8.0%) PCR-positive T. gondii samples revealed homology and genetic heterogeneity with T. gondii strains in the GenBank, except for only one positive sample that did not show a result. There was almost perfect agreement (k = 0.145) between the two PCR assays targeting the B1 gene and the REP gene. This is the first report on microscopic, molecular detection and genetic diversity of T. gondii from cat faecal samples in Malaysia. In addition, the sensitivities of either the B1 gene or REP gene multicopy-target PCR assays are suitable for the accurate detection of T. gondii from cat faeces.
Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice

Jabbarzare M, Chin VK, Talib H, Yam MF, Adam SK, Hassan H, et al.

Iran J Parasitol, 2015 Jul-Sep;10(3):389-401.
PMID: 26622294

Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice.
Fulltext Interleukin-27 exhibited anti-inflammatory activity during Plasmodium berghei infection in mice

Fazalul Rahiman SS, Basir R, Talib H, Tie TH, Chuah YK, Jabbarzare M, et al.

Trop Biomed, 2013 Dec;30(4):663-80.
PMID: 24522137 MyJurnal

Interleukin-27 (IL-27) has a pleiotropic role either as a pro-inflammatory or anti-inflammatory cytokine in inflammatory related diseases. The role and involvement of IL-27 during malaria was investigated and the effects of modulating its release on the production of major inflammatory cytokines and the histopathological consequences in major affected organs during the infection were evaluated. Results showed that IL-27 concentration was significantly elevated throughout the infection but no positive correlation with the parasitaemia development observed. Augmentation of IL-27 significantly elevated the release of anti-inflammatory cytokine, IL-10 whereas antagonising and neutralising IL-27 produced the opposite. A significant elevation of pro-inflammatory cytokines (IFN-γ and IL-6) was also observed, both during augmentation and inhibition of IL-27. Thus, it is suggested that IL-27 exerts an anti-inflammatory activity in the Th1 type response by signalling the production of IL-10 during malaria. Histopathological examination showed sequestration of PRBC in the microvasculature of major organs in malarial mice. Other significant histopathological changes include hyperplasia and hypertrophy of the Kupffer cells in the liver, hyaline membrane formation in lung tissue, enlargement of the white and red pulp followed by the disappearance of germinal centre of the spleen, and tubular vacuolation of the kidney tissues. In conclusion, it is suggested that IL-27 may possibly acts as an anti-inflammatory cytokine during the infection. Modulation of its release produced a positive impact on inflammatory cytokine production during the infection, suggesting its potential in malaria immunotherapy, in which the host may benefit from its inhibition.
Fulltext Investigation of Andrographolide Effect on Non-Infected Red Blood Cells Using the 1H-NMR-Based Metabolomics Approach

Alapid AAI, Abd Majid R, Ibraheem ZO, Mediani A, Ismail IS, Unyah NZ, et al.

Metabolites, 2021 Jul 28;11(8).
PMID: 34436427 DOI: 10.3390/metabo11080486

Andrographolide (AG) has been shown to have several medicinal and pharmaceutical effects, such as antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, and anti-malarial activities. Moreover, studies to assess the pharmacological effect of AG on the metabolic changes of uninfected red blood cells (uRBCs) have not yet been investigated. This study aims to evaluate the pharmacological effects of AG compared to chloroquine (CQ) on the metabolic variations of uRBCs in vitro using a proton nuclear magnetic resonance (1H-NMR)-based metabolomics approach coupled with multivariate data analysis (MVDA). Forty-one metabolites were successfully identified by 1H-NMR. The results of the unsupervised data analysis principal component analysis (PCA) showed ideal differentiation between AG and CQ. PC1 and PC2 accounted for 71.4% and 17.7% of the explained variation, respectively, with a total variance of 89.10%. Based on S-plot and VIP values, a total of 28 and 32 metabolites were identified as biomarkers in uRBCs-AG and uRBCs-CQ, respectively. In uRBCs treated with AG, ten metabolic pathways were determined to be disturbed, including riboflavin metabolism, d-glutamate and d-glutamine metabolism, phenylalanine metabolism, glutathione metabolism, proline and arginine metabolism, arginine biosynthesis, citrate cycle, glycolysis/gluconeogenesis, and pyruvate metabolism as well as alanine, aspartate, and glutamate metabolism. In contrast, in CQ-treated uRBCs, nine affected metabolic pathways were determined, which involved the same metabolic pathways for uRBCs-AG, except for glutathione metabolism. These findings suggest an evident relationship between AG and CQ associated with metabolic changes in intact RBCs after being exposed to the treatment. The metabolomics results could allow useful comprehensive insights into the underlying mechanism of the action of AG and CQ on red blood cells. Consequently, the 1H-NMR-based metabolomics approach was successfully utilized to identify the pharmacological effects of AG and CQ on the metabolic variations of uRBCs.
Fulltext The Role, Involvement and Function(s) of Interleukin-35 and Interleukin-37 in Disease Pathogenesis

Bello RO, Chin VK, Abd Rachman Isnadi MF, Abd Majid R, Atmadini Abdullah M, Lee TY, et al.

Int J Mol Sci, 2018 Apr 11;19(4).
PMID: 29641433 DOI: 10.3390/ijms19041149

The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis. Either cytokine has been reported to be reduced and in some cases elevated and consequently contributed towards disease pathogenesis. In view of the recent advances in utilizing cytokine profiles for the development of biological macromolecules, beneficial in the management of certain intractable immune-mediated disorders, these recently characterized cytokines (IL-35 and IL-37) offer potential as reasonable targets for the discovery of novel immune-modulating anti-inflammatory therapies. A detailed comprehension of their sophisticated regulatory mechanisms and patterns of expression may provide unique opportunities for clinical application as highly selective and target specific therapeutic agents. This review seeks to summarize the recent advancements in discerning the dynamics, mechanisms, immunoregulatory and anti-inflammatory actions of IL-35 and IL-37 as they relate to disease pathogenesis.
Fulltext IL35 modulation altered survival, cytokine environment and histopathological consequences during malaria infection in mice

Bello RO, Abdullah MA, Abd Majid R, Chin VK, Abd Rachman Isnadi MF, Ibraheem ZO, et al.

Malar J, 2019 Dec 19;18(1):434.
PMID: 31856836 DOI: 10.1186/s12936-019-3070-x

BACKGROUND: The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequent upon the recognition of inflammatory cytokine activation and its preponderance for mediating pathology during malaria infection, the study aimed to characterize the expression and functional contribution(s) of IL-35 in Plasmodium berghei (strain ANKA) infected mice.
METHODS: Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and disease progression was evaluated.
RESULTS: Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice.
CONCLUSION: These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection.
Fulltext A Review on the Prevalence of Toxoplasma gondii in Humans and Animals Reported in Malaysia from 2008-2018

Nasiru Wana M, Mohd Moklas MA, Watanabe M, Nordin N, Zasmy Unyah N, Alhassan Abdullahi S, et al.

Int J Environ Res Public Health, 2020 07 03;17(13).
PMID: 32635389 DOI: 10.3390/ijerph17134809

Toxoplasmosis is a disease caused by the protozoan parasite Toxoplasma gondii (T. gondii). Human toxoplasmosis seroprevalence in Malaysia has increased since it was first reported in 1973 as shown in previous reviews of 1991 and 2007. However, over a decade since the last review, comprehensive data on toxoplasmosis in Malaysia is lacking. This work aimed at reviewing articles on toxoplasmosis research in Malaysia in order to identify the research gaps, create public awareness, and efforts made so far and proffer management options on the disease. The present review examines the available published research articles from 2008 to 2018 related to toxoplasmosis research conducted in Malaysia. The articles reviewed were retrieved from nine credible databases such as Web of Science, Google Scholar, ScienceDirect, PubMed, Scopus, Springer, Wiley online library, Ovid, and Cochrane using the keywords; Malaysia, toxoplasmosis, Toxoplasma gondii, toxoplasma encephalitis, seroprevalence, human immunodeficiency virus (HIV) patients, pregnant women, genotype strain, anti-toxoplasma antibodies, felines, and vaccine. The data highlighted seropositive cases from healthy community members in Pangkor Island (59.7%) and among migrant workers (57.4%) at alarming rates, as well as 42.5% in pregnant women. Data on animal seroprevalence were limited and there was no information on cats as the definitive host. Genetic characterization of Toxoplasma gondii from HIV patients; pregnant women, and domestic cats is lacking. This present review on toxoplasmosis is beneficial to researchers, health workers, animal health professionals, and policymakers. Therefore, attention is required to educate and enlighten health workers and the general public about the risk factors associated with T. gondii infection in Malaysia.
Targeting 8-oxoguanine DNA glycosylase-1 (OGG1) as a therapeutic strategy in inflammatory-related diseases

Samaila A, Basir R, Gambo Lawal M, Abas R, Abdullah MA, Abd Majid R, et al.

Immunopharmacol Immunotoxicol, 2024 Aug 20.
PMID: 39164801 DOI: 10.1080/08923973.2024.2391471

OBJECTIVE: Inflammatory diseases are influenced by oxidative stress. Oxidatively damaged 8-oxoG in DNA is linked to inflammation. The enzyme OGG1 is responsible for repairing the damaged base in the DNA which is linked to pro-inflammatory signaling and severe inflammation. This study aims to explore the potential of targeting OGG1 as a therapeutic strategy in inflammatory disease conditions.
METHODS: A comprehensive search and review of literature were conducted using appropriate scientific databases such as Google Scholar, Scopus, PubMed, Web of Science, and other references to obtain relevant information that suited the title and content of this article.
RESULTS: Compelling pieces of evidence from many previous studies have shown the crucial role of the OGG1/8oxoG pathway in inflammatory disease conditions, leading to severe inflammatory response and death. Therefore, based on these pieces of evidence, targeting this enzyme (OGG1) using specific pharmacological inhibitors or interventions might lead to downregulation and amelioration of severe inflammation to reduce the morbimortality related to several disease conditions.
CONCLUSION: This review highlighted the molecular mechanism of OGG1 activity via the 8-oxo/OGG1 pathway and its role in inflammation and inflammatory disease conditions. Due to the paucity of studies involving OGG1in inflammatory infectious diseases, further research projects are needed to explore the therapeutic potential of various OGG1 inhibitors to serve as novel therapeutic strategies in infectious inflammatory diseases of medical importance in developing countries such as malaria, meningitis, tuberculosis among others.

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