In vitro Anti-inflammatory Evaluation of 6-Thioguanine and  6-Hydroxy-2-Mercaptopurine as A Potential Treatment for Rheumatoid Arthritis

Nordin, N.; Yong, Yoke Keong; Tohid, Siti Farah Md; Zain, Zetty Nadia Md; Somchit, M. N.

doi:10.18585/inabj.v13i4.1650

Cited by 3 publications

(3 citation statements)

References 27 publications

(29 reference statements)

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“…This may be due to a more significant reduction of inflammatory cytokines with 6-TG and F-ara therapy compared to AZA. 6-TG and F-ara has also been shown to reduce circulating lymphocytes by 42% and 30% and WBC levels by 15%, 9,26,27 while AZA has been shown to reduce lymphocytes by 23% respectively. 28 Age stratification of the study population revealed that PJP cases were prominent in the pediatric population with approximately 2 times more risk than the adult population.…”

Section: Discussionmentioning

confidence: 98%

Purine antimetabolites associated Pneumocystis jirovecii pneumonia

Lukose,

Shantaram,

Raj

et al. 2023

Pharmacoepidemiology and Drug

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PurposeTo detect the possible safety signal of purine antimetabolites associated with Pneumocystis jirovecii pneumonia through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database.MethodsA case/non‐case retrospective disproportionality analysis was performed in the publicly available FAERS database using AERSmine (2004Q1–2021Q3). Four models were developed to explore the signal strength of PAs among different populations with possible confounding factors. Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) was used as the data mining algorithm for the analysis. A value of ROR‐1.96SE > 1 and PRR ≥ 2 with an associated X2 value of 4 or more was considered the threshold for a signal.ResultsA total of 7073 reports associated with Pneumocystis jirovecii pneumonia were present in the database, of which 899 reports were associated with purine antimetabolites. A crude signal strength of ROR 15.76(14.70–16.91) was obtained for purine antimetabolites associated PJP, with the highest signal strength reported with fludarabine and thioguanine [ROR 19.63(17.42–22.13); 19.45(13.21–28.63)]. Stratifying the cases based on autoimmune disorders and the cancer population revealed an ROR of 3.33(2.46–4.50) and 2.93(2.26–3.79) respectively. The highest risk of PJP with use of PAs was observed amongst children with a higher risk of nearly 2 times than the adult population [ROR 11.57(9.16–14.62)].ConclusionsOur study provided evidence on the occurrence of PJP with the use of purine antimetabolites among the autoimmune and cancer population. We identified signals for PJP with azathioprine, mercaptopurine, thioguanine, cladribine, fludarabine, and clofarabine. More research with a superior epidemiological study design of a defined population is required to validate these findings.

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Section: Discussionmentioning

confidence: 98%

Purine antimetabolites associated Pneumocystis jirovecii pneumonia

Lukose,

Shantaram,

Raj

et al. 2023

Pharmacoepidemiology and Drug

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“…7 The results of this study agree with several studies who reported that NO production in cell line was inhibited by showing anti-inflammatory activity. (30)(31)(32) In many mammalian cells and tissues, L-arginine produces NO and iNOS via constitutive. (6) The expression of neuronal NOS (nNOS) and endothelial NOS (eNOS) is an important factor that regulates homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Bifidobacterium lactis Inhibits iNOS Expression in LPS-stimulated RAW 264.7 Macrophages

Negara

Choi

2022

Indones Biomed J

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BACKGROUND: Bifidobacterium is a genus of lactic acid bacteria that lives in the large intestine of humans and animals. The health benefits of this genus are well established; however, the anti-inflammatory activity of this genus, specifically Bifidobacterium lactis, has not been well defined. Therefore, in this study, we evaluated anti-inflammatory activity of B. lactis hydrolysates using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.METHODS: RAW 264.7 cells were cultured using Dulbecco’s Modified Eagle’s Medium in 5 % CO2 incubator at 37 ℃. One µg/mL of LPS was used to stimulate RAW 264.7 cells. Nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were measured to evaluate anti-inflammatory activity of B. lactis hydrolysates. The cytotoxicity of the inhibitor was also measured in present study through 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay.RESULTS: The results showed that B. lactis hydrolysates at 25–200 μg/mL inhibited NO production. In concentration-dependent manner, B. lactis hydrolysate showed inhibition of iNOS expression. However, no inhibition on COX-2 expression was observed. The MTS assay of the B. lactis hydrolysates showed no side effects on the cell viability at all concentrations.CONCLUSION: The current study revealed that B. lactis hydrolysates possess specific anti-inflammatory effects by inhibiting iNOS expression without cytotoxicity and therefore could potentially be developed as a new iNOS inhibitor.KEYWORDS: Bifidobacterium lactis, macrophages, hydrolysates, iNOS, COX-2

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“…This layer triggers the production of cytokines. 22,[27][28][29][30] The Gram-positive component is recognized by TLR2 and TLR4 while the Gram-negative component is only recognized by TLR4. This causes a large influx of neutrophils and increases TNF-α levels higher in Gram-positive bacterial infections.…”

Section: Types Of Bacteriamentioning

confidence: 99%

High TNF-α Levels in Active Phase Chronic Suppurative Otitis Media Caused by Gram-positive Bacteria

Dewi¹,

Pratiwi²,

Kandhi³

2023

Mol Cell Biomed Sci

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Background: Chronic suppurative otitis media (CSOM) is a persistent inflammatory disease of the middle ear and mastoid cavity caused by pathogenic infection. CSOM has a fairly high incidence in developing countries and is the main cause of acquired hearing loss in children. Tumor necrosis factor alpha (TNF-α) is a significant inflammatory mediator in CSOM. This study aimed to analyze TNF-α levels in ear discharge and blood serum in active phase CSOM caused by Gram-positive and Gram-negative bacteria.Materials and Methods: This research was an analytical observational study with a cross sectional design. Blood serum and ear discharge from CSOM patients were used in this study. Blood serum and ear discharge TNF-α levels were measured using enzyme-linked immunosorbent assay.Results: From 26 CSOM subjects, 13 subjects were infected with Gram-positive bacteria and the 13 others were infected with Gram-negative bacteria. The majority of the subjects were male (53.8%) with an age range from 36-45 years (42.3%). The most common species of bacteria was Pseudomonas aeruginosa. Blood serum and ear discharge TNF-α levels were higher in samples that contained Gram-positive bacteria.Conclusion: TNF-α levels in active phase CSOM caused by Gram-positive bacteria are higher than those which are caused by Gram-negative bacteria.Keywords: chronic suppurative otitis media, TNF-α, gram-positive, gram-negative

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In vitro Anti-inflammatory Evaluation of 6-Thioguanine and 6-Hydroxy-2-Mercaptopurine as A Potential Treatment for Rheumatoid Arthritis

Cited by 3 publications

References 27 publications

Purine antimetabolites associated Pneumocystis jirovecii pneumonia

Purine antimetabolites associated Pneumocystis jirovecii pneumonia

Bifidobacterium lactis Inhibits iNOS Expression in LPS-stimulated RAW 264.7 Macrophages

High TNF-α Levels in Active Phase Chronic Suppurative Otitis Media Caused by Gram-positive Bacteria

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