دورية أكاديمية
Nrf2 inhibition induces oxidative stress, renal inflammation and hypertension in mice.
| العنوان: | Nrf2 inhibition induces oxidative stress, renal inflammation and hypertension in mice. |
|---|---|
| المؤلفون: | Farooqui Z; Heart and Kidney Institute, College of Pharmacy, University of Houston , Houston, Texas, USA., Mohammad RS; Heart and Kidney Institute, College of Pharmacy, University of Houston , Houston, Texas, USA., Lokhandwala MF; Heart and Kidney Institute, College of Pharmacy, University of Houston , Houston, Texas, USA., Banday AA; Heart and Kidney Institute, College of Pharmacy, University of Houston , Houston, Texas, USA. |
| المصدر: | Clinical and experimental hypertension (New York, N.Y. : 1993) [Clin Exp Hypertens] 2021 Feb 17; Vol. 43 (2), pp. 175-180. Date of Electronic Publication: 2020 Oct 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 9305929 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-6006 (Electronic) Linking ISSN: 10641963 NLM ISO Abbreviation: Clin Exp Hypertens Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : Informa Healthcare Original Publication: New York, N.Y. : Marcel Dekker, Inc., c1993- |
| مواضيع طبية MeSH: | Hypertension*/etiology , Hypertension*/metabolism , Hypertension*/physiopathology , NF-E2-Related Factor 2*/antagonists & inhibitors , NF-E2-Related Factor 2*/genetics , NF-E2-Related Factor 2*/metabolism , NF-E2-Related Factor 2*/pharmacology , Reactive Oxygen Species*/metabolism , Reactive Oxygen Species*/pharmacology, Buthionine Sulfoximine/*pharmacology, Animals ; Antioxidants/pharmacology ; Blood Pressure/drug effects ; Enzyme Inhibitors/pharmacology ; Gene Expression Regulation ; Inflammation/etiology ; Inflammation/metabolism ; Kidney/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress/drug effects |
| مستخلص: | Oxidative stress and renal inflammation play a pivotal role in the pathogenesis of hypertension. The redox-sensitive transcription factor, nuclear factor E2-related factor 2 (Nrf2) is the master regulator of phase II antioxidant enzymes that protects against oxidative stress and inflammation. This study aimed to investigate the effect of Nrf2 inhibition on oxidative stress-associated hypertension and renal dopamine 1 receptor (D1R) dysfunction in mice. Male C57BL/6 J mice were treated with a pro-oxidant, L-buthionine sulfoximine (BSO) (10 mmol/L in drinking water), and ML385 (10 kg body weight/kg body weight/day, intraperitoneally), a novel Nrf2 inhibitor that blocks Nrf2 regulated downstream target genes expression. Mice treated with BSO exhibited oxidative stress, renal functional impairment, inflammation, and elevated blood pressure. Also, BSO treatment increased the activity of phase II antioxidant enzyme, NAD(P)H: quinone oxidoreductase-1 (NQO-1). BSO and ML385 co-treatment exhibited a robust increase in blood pressure, oxidative stress and intensified the renal function deterioration as indicated by a significant increase in serum creatinine, urinary albumin excretion rate, and albumin to creatinine ratio and decreased glomerular filtration rate (GFR). Also, BSO and ML385 co-treatment downregulated NQO-1 and significantly altered the inflammatory cytokines, IL-1β and IL-10 levels. A D1R agonist SKF38393 failed to promote urinary sodium excretion indicating functional impairment in renal D1R. ML385 per se did not affect mean arterial pressure, GFR, and renal D1R function. Taken together, we concluded that the Nrf2 inhibition aggravated oxidative stress and inflammation by diminishing phase II antioxidant defense that deteriorates renal function and contributes to the development of hypertension in mice. |
| References: | Hypertension. 2015 Apr;65(4):896-902. (PMID: 25691623) Toxicol Appl Pharmacol. 2014 Jan 15;274(2):293-301. (PMID: 24211276) Int Immunopharmacol. 2019 Jul;72:445-453. (PMID: 31035086) Hypertension. 2013 Sep;62(3):512-7. (PMID: 23876469) ACS Chem Biol. 2016 Nov 18;11(11):3214-3225. (PMID: 27552339) Kidney Int. 2007 Mar;71(5):397-406. (PMID: 17191082) Methods Mol Biol. 2018;1816:207-220. (PMID: 29987822) Cardiovasc Hematol Agents Med Chem. 2006 Oct;4(4):369-77. (PMID: 17073613) Diabetes. 2005 Jul;54(7):2219-26. (PMID: 15983225) Oxid Med Cell Longev. 2019 Sep 2;2019:9719618. (PMID: 31565157) Am J Physiol Renal Physiol. 2004 Mar;286(3):F451-7. (PMID: 14612382) Toxicol Appl Pharmacol. 2017 Oct 15;333:100-109. (PMID: 28842207) Aging Dis. 2019 Jun 01;10(3):637-651. (PMID: 31165007) Medicine (Baltimore). 2015 Nov;94(47):e2160. (PMID: 26632749) Hypertension. 2015 Dec;66(6):1240-50. (PMID: 26503970) JAMA. 2014 Feb 5;311(5):507-20. (PMID: 24352797) Oxid Med Cell Longev. 2018 Apr 26;2018:7161592. (PMID: 29854090) J Am Heart Assoc. 2020 Jan 7;9(1):e014977. (PMID: 31880979) Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F141-F144. (PMID: 28404590) Int J Mol Sci. 2019 Aug 14;20(16):. (PMID: 31416234) Int J Hypertens. 2019 May 2;2019:3159283. (PMID: 31186952) Oxid Med Cell Longev. 2019 Jun 23;2019:7092151. (PMID: 31341533) Am J Physiol Regul Integr Comp Physiol. 2015 May 15;308(10):R840-6. (PMID: 25761698) Hypertension. 2015 May;65(5):1064-72. (PMID: 25733244) Antioxid Redox Signal. 2014 Jan 1;20(1):102-20. (PMID: 23472597) Physiol Res. 2016 Sep 19;65 Suppl 1:S1-S10. (PMID: 27643930) Curr Hypertens Rep. 2010 Apr;12(2):135-42. (PMID: 20424957) Medicina (Kaunas). 2016;52(1):19-27. (PMID: 26987496) Food Chem Toxicol. 2014 Sep;71:264-71. (PMID: 24975872) Sci Rep. 2016 Oct 07;6:34246. (PMID: 27713551) Free Radic Biol Med. 2016 Aug;97:58-74. (PMID: 27223823) J Biochem Mol Biol. 2004 Mar 31;37(2):139-43. (PMID: 15469687) Hypertens Res. 2011 Apr;34(4):431-40. (PMID: 21228777) J Res Med Sci. 2014 Apr;19(4):358-67. (PMID: 25097610) Free Radic Biol Med. 2009 Nov 1;47(9):1304-9. (PMID: 19666107) Am J Hypertens. 2012 Feb;25(2):229-35. (PMID: 22052072) Int J Mol Sci. 2013 Aug 27;14(9):17553-72. (PMID: 23985827) Biomed Res Int. 2014;2014:406960. (PMID: 25136585) |
| معلومات مُعتمدة: | R01 HL139808 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: ML385; NRF2; Oxidative stress; hypertension; inflammation |
| المشرفين على المادة: | 0 (Antioxidants) 0 (Enzyme Inhibitors) 0 (NF-E2-Related Factor 2) 0 (Nfe2l2 protein, mouse) 0 (Reactive Oxygen Species) 5072-26-4 (Buthionine Sulfoximine) |
| تواريخ الأحداث: | Date Created: 20201019 Date Completed: 20210517 Latest Revision: 20220218 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7790982 |
| DOI: | 10.1080/10641963.2020.1836191 |
| PMID: | 33070655 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1525-6006 |
|---|---|
| DOI: | 10.1080/10641963.2020.1836191 |