Objectives: The purpose of this study was to determine whether the 347 C/G polymorphism in the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) gene predicts the responsiveness to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA).
Method: To identify relevant publications, we searched the Medline, Embase, Cochrane, and Web of Science databases. We performed a meta-analysis of studies on the relationship between the ATIC 347 C/G polymorphism and MTX toxicity or non-responsiveness in patients with RA.
Results: Thirteen studies consisting of 3,185 patients with RA satisfied our inclusion criteria. The analysis included 10 studies on MTX responsiveness and seven studies on MTX toxicity in patients with RA in connection with ATIC 347C/G polymorphism. According to our meta-analysis, the ATIC 347 GG genotype and failure to respond to MTX treatment were significantly associated (OR = 0.741, 95% CI = 0.591-0.929, p=0.009). According to stratification by ethnicity, this genotype was significantly associated with non-responsiveness to MTX in Europeans (OR=0.548, 95% CI=0.377-0.796, p=0.002) but not in Asian populations (OR=0.882, 95% CI=0.665-1.1172, p=0.388). However, analyses employing allelic, dominant, and homozygous contrast models failed to detect any relationship between the polymorphism and the failure to respond to MXT. However, the ATIC 347GG genotype and MTX toxicity were not associated (OR=1.278, 95% CI=0.937-1.745, p=0.121). Asian and European populations showed no evidence of a relationship between the ATIC 347GG genotype and MTX toxicity (OR=1.252, 95% CI=0.905-1.732, p=0.175 and OR =1.617, 95% CI=0.549-4.765, p=0.383, respectively).
Conclusions: This meta-analysis revealed that ATIC 347 C/G polymorphism was related to non-responsiveness to MTX in European populations with RA. However, no significant correlation was found with MTX toxicity.
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http://dx.doi.org/10.1016/j.semarthrit.2023.152337 | DOI Listing |
Nanotoxicology
January 2025
Department of Pharmaceutical Sciences & Administration, School of Pharmacy, Westbrook College of Health Professions, University of New England, Portland, Maine, USA.
Important cell-based models of intestinal inflammation have been advanced in hopes of predicting the impact of nanoparticles on disease. We sought to determine whether a high level and extended exposure of nanoplastic might result in the added intestinal inflammation caused by nanoplastic reported in a mouse model of irritable bowel disease. The cell models consist of a Transwell©-type insert with a filter membrane upon which lies a biculture monolayer of Caco-2 and HT29-MTX-E12 made up the barrier cells (apical compartment).
View Article and Find Full Text PDFToxicol Res (Camb)
February 2025
College of Pharmacy, Al-Mustaqbal University, Babylon Province, Najaf Road, Hillah 51001, +964, Iraq.
Methotrexate (MTX) is an antimetabolite drug utilized for managing a variety of cancers and autoinflammatory conditions. MTX may trigger detrimental effects in mout, h tissues, including salivary gland impairment. Bosentan (BOS), a drug that blocks endothelin receptors, has strengthened antioxidant, anti-inflammatory, and anti-apoptotic properties.
View Article and Find Full Text PDFCancer Med
January 2025
Clinical Research Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Background: 7-Hydroxymethotrexate (7-OHMTX) is the main metabolite in plasma following high-dose MTX (HD-MTX), which may result in activity and toxicity of the MTX. Moreover, 7-OHMTX could produce crystalline-like deposits within the renal tubules under acidic conditions or induce renal inflammation, oxidative stress, and cell apoptosis through various signaling pathways, ultimately leading to kidney damage. The objectives of this study were thus to explore the exposure-safety relationship of two compounds and search the most reliable marker for predicting HDMTX nephrotoxicity.
View Article and Find Full Text PDF<b>Background and Objective:</b> Methotrexate is an anti-metabolic medication used to treat cancer. It causes oxidative stress in nerve tissue and has neurotoxic effects. A strong antioxidant and effective free radical scavenger is vitamin C.
View Article and Find Full Text PDFInt J Pharm X
June 2025
State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China.
Systemic administration of methotrexate (MTX), widely regarded as one of the most effective treatments for psoriasis, poses significant challenges due to its high toxicity, limited solubility, and potential for adverse effects. Consequently, developing a topical form of MTX may offer a safer and more effective strategy for psoriasis management. Silk fibroin (SF), a protein-based biomacromolecule, has shown considerable promise as a nanocarrier for sustained and targeted drug delivery, owing to its exceptional physicochemical and biological properties.
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