The role of oxidative stress-mediated apoptosis in the pathogenesis of uric acid nephropathy.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 8701128 Publication Model: Print Cited Medium: Internet ISSN: 1525-6049 (Electronic) Linking ISSN: 0886022X NLM ISO Abbreviation: Ren Fail Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: New York, N.Y. : M. Dekker, c1987-

Apoptosis* ; Oxidative Stress*; Glutathione/*pharmacology ; Kidney/*physiopathology ; Mitochondria/*pathology ; Uric Acid/*pharmacology; Animals ; Apoptosis Regulatory Proteins/metabolism ; Caspase 3/metabolism ; Caspase 9/metabolism ; Creatinine/blood ; Male ; Malondialdehyde/metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase/metabolism

Objective: By copying the uric acid nephropathy rat model, the oxidative stress injury of mitochondria was caused in renal tubular epithelial cells and the relationship between the injury and the induction of cell apoptosis was identified. Methods: All rats were randomly divided into NC (normal control, NC) group, HUA (high uric acid, HUA) group and GSH (reductive glutathione, GSH) group. The values were quantitatively tested in the kidney tissues, including 24-h urinary protein quantity, serum creatinine, blood uric acid, the MDA (malondialdehyde, MDA) and SOD (superoxide dismutase, SOD) oxidative stress indicators. The expression of p53, Bax and caspase-9/-3 were detected by immunoblotting. TUNEL assays were used to detect the apoptosis of renal tubular epithelial cells. Result: In HUA and GSH groups, the 24-h urinary protein(24UTP), serum creatinine, and blood uric acid increased gradually with the increase of the replication cycle and the increase was significant compared to the NC group ( p  < .05). Compared to the NC group, MDA increased whereas SOD decreased. The expression of apoptotic proteins, such as p53, Bax, and caspase-9/-3 in the mitochondria was significantly different ( p  < .05). TUNEL assay revealed that the renal tubular epithelial cells in HUA group were largely apoptotic, whereas the GSH group improved significantly. Conclusion: Mitochondria incurred the substantial damage due to being in a state of oxidative stress, which was the primary cause of apoptosis in the renal tubule epithelial cells. GSH exhibited the effective resistance to the influence of oxidative stress and can restore the damage in the renal tubular epithelial cells.

Eur Heart J. 2011 Mar;32(6):712-20. (PMID: 21199831)
Anticancer Drugs. 2013 Mar;24(3):260-9. (PMID: 23187459)
Am J Physiol Renal Physiol. 2013 Mar 1;304(5):F471-80. (PMID: 23283992)
Antioxid Redox Signal. 2014 Apr 1;20(10):1646-54. (PMID: 23886445)
Evid Based Complement Alternat Med. 2014;2014:834815. (PMID: 24991228)
Oncotarget. 2014 Sep 30;5(18):8452-65. (PMID: 25115399)
PLoS One. 2014 Sep 03;9(9):e105577. (PMID: 25184445)
Oxid Med Cell Longev. 2015;2015:535686. (PMID: 25918583)
J Psychiatr Res. 2016 Jan;72:43-50. (PMID: 26540403)
BMC Genomics. 2016 Jan 16;17:62. (PMID: 26772977)
Genes Dev. 2016 Apr 15;30(8):973-88. (PMID: 27056669)
J Atheroscler Thromb. 2017 Jun 1;24(6):630-642. (PMID: 27784849)
Oncotarget. 2016 Dec 27;7(52):86211-86224. (PMID: 27863415)
Oxid Med Cell Longev. 2016;2016:9707292. (PMID: 27872680)
Oncotarget. 2017 Jun 20;8(25):40305-40317. (PMID: 28445133)
Front Plant Sci. 2017 Jun 13;8:1010. (PMID: 28659953)
Med Oral Patol Oral Cir Bucal. 2018 Mar 1;23(2):e120-e125. (PMID: 29476674)

Keywords: Uric acid nephropathy; apoptosis; mitochondria; oxidative stress; reduced glutathione

0 (Apoptosis Regulatory Proteins)
268B43MJ25 (Uric Acid)
4Y8F71G49Q (Malondialdehyde)
AYI8EX34EU (Creatinine)
EC 1.15.1.1 (Superoxide Dismutase)
EC 3.4.22.- (Caspase 3)
EC 3.4.22.- (Caspase 9)
GAN16C9B8O (Glutathione)

Date Created: 20190705 Date Completed: 20200115 Latest Revision: 20200225

20231215

PMC6610514

10.1080/0886022X.2019.1633350

31269852