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Diabetes aggravates renal ischemia and reperfusion injury in rats by exacerbating oxidative stress, inflammation, and apoptosis
| Content Provider | Scilit |
|---|---|
| Author | Gong, Dao-Jing Wang, Lei Yang, Yuan-Yuan Zhang, Jian-Jian Liu, Xiu-Heng |
| Copyright Year | 2019 |
| Description | Diabetic patients are more susceptible to renal ischemia/reperfusion (I/R) injury (RI/RI) and have a poor prognosis, but the underlying mechanism remains unclear. The present study aimed to examine whether diabetes could worsen acute kidney injury induced by I/R in rats and clarify its mechanism. Control and streptozotocin-induced diabetic rats were subjected to 45 min renal pedicle occlusion followed by 24 h reperfusion. Tert-butylhydroquinone (TBHQ, 16.7 mg/kg) was administrated intraperitoneally 3 times at intervals of 8 h before ischemia. Serum and kidneys were harvested after reperfusion to evaluate renal function and histological injury. Enzyme-linked immunosorbent assays were used to test pro-inflammatory cytokines. Terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling assays were used to detect apoptotic cells, and western blotting was performed to determine the expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3, as well as oxidative stress and inflammation-related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB). Compared with control animals, diabetic rats undergoing I/R exhibited more severe tubular damage and renal dysfunction. Diabetes exacerbated oxidative stress, the inflammatory response, and apoptosis after renal I/R by enhancing TLR4/NF-κB signaling and blocking the Nrf2/HO-1 pathway. RI/RI in diabetic rats was attenuated by pretreatment with TBHQ (a Nrf2 agonist), which exerted anti-inflammatory and anti-apoptotic properties by inhibiting NF-κB signaling. These findings indicate that hyperglycemia exacerbates RI/RI by intensifying oxidative stress, inflammation, and apoptosis. Antioxidant pretreatment may alleviate RI/RI in diabetic patients. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.1080/0886022X.2019.1643737?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720228/pdf |
| Ending Page | 761 |
| Page Count | 12 |
| Starting Page | 750 |
| ISSN | 0886022X |
| e-ISSN | 15256049 |
| DOI | 10.1080/0886022x.2019.1643737 |
| Journal | Renal Failure |
| Issue Number | 1 |
| Volume Number | 41 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2019-01-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Renal Failure Biochemistry and Molecular Biology Diabetes Mellitus Ischemia-reperfusion Oxidative Stress Inflammation Acute Kidney Injury Apoptosis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Critical Care and Intensive Care Medicine Nephrology |