دورية أكاديمية
Omeprazole induces profibrotic gene expression in rat kidney: implication of TGF-β/Smad signaling pathway.
| العنوان: | Omeprazole induces profibrotic gene expression in rat kidney: implication of TGF-β/Smad signaling pathway. |
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| المؤلفون: | Allam A; Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Ali AA; Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Abdel Baky NA; Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Balah A; Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt. |
| المصدر: | Drug and chemical toxicology [Drug Chem Toxicol] 2024 Sep; Vol. 47 (5), pp. 748-755. Date of Electronic Publication: 2023 Nov 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Group Country of Publication: United States NLM ID: 7801723 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-6014 (Electronic) Linking ISSN: 01480545 NLM ISO Abbreviation: Drug Chem Toxicol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: [Philadelphia, PA] : Taylor & Francis Group Original Publication: New York, Dekker. |
| مواضيع طبية MeSH: | Signal Transduction*/drug effects , Omeprazole*/pharmacology , Proton Pump Inhibitors*/pharmacology , Kidney*/drug effects , Kidney*/metabolism , Transforming Growth Factor beta*/metabolism , Transforming Growth Factor beta*/genetics , Connective Tissue Growth Factor*/genetics , Connective Tissue Growth Factor*/metabolism , Tissue Inhibitor of Metalloproteinase-1*/metabolism , Tissue Inhibitor of Metalloproteinase-1*/genetics, Animals ; Male ; Rats ; Fibrosis ; Reactive Oxygen Species/metabolism ; Smad Proteins/metabolism ; Smad Proteins/genetics ; Gene Expression Regulation/drug effects ; Rats, Wistar |
| مستخلص: | Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications. However, PPI usage is linked to a higher risk of both acute and chronic renal damage by mechanisms not entirely known. The present study demonstrates that omeprazole (10 mg/kg body weight, i.p.) causes TGF-β/Smad signaling activation and subsequent expression of the profibrotic genes CTGF and TIMP-1 in rat kidney. Increased production of CTGF and TIMP-1 accompany activation of the TGF-β/Smad signaling cascade. However, simultaneous treatment of omeprazole and the TGF-β inhibitor, disitertide (P144) (1 mg/kg body weight i.p.) suppresses the TGF-β/Smad signaling pathway and subsequent production of CTGF and TIMP-1. Additionally, TGF-β level in rat kidney was highly reduced in animals treated with the ROS (reactive oxygen species) scavenger, N-acetyl cysteine (NAC) (100 mg/kg body weight i.p.) before omeprazole administration. Furthermore, the reduction in SOD activity brought by omeprazole was returned to the normal level in those animals. However, MDA level increased by omeprazole was highly reduced in the presence of NAC. Collectively, the current findings demonstrate that omeprazole has the ability to promote the expression of the profibrotic genes CTGF and TIMP-1 in a ROS and TGF-β dependent manner. The present study suggests the co-use of ROS scavenger to improve the therapeutic use of the PPI omeprazole. |
| فهرسة مساهمة: | Keywords: Omeprazole; ROS; TGF-β/Smad signaling; fibrosis; kidney |
| المشرفين على المادة: | KG60484QX9 (Omeprazole) 0 (Proton Pump Inhibitors) 0 (CCN2 protein, rat) 0 (Transforming Growth Factor beta) 139568-91-5 (Connective Tissue Growth Factor) 0 (Tissue Inhibitor of Metalloproteinase-1) 0 (TIMP1 protein, rat) 0 (Reactive Oxygen Species) 0 (Smad Proteins) |
| تواريخ الأحداث: | Date Created: 20231120 Date Completed: 20240903 Latest Revision: 20240905 |
| رمز التحديث: | 20240906 |
| DOI: | 10.1080/01480545.2023.2282377 |
| PMID: | 37982208 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1525-6014 |
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| DOI: | 10.1080/01480545.2023.2282377 |