Telmisartan attenuates diabetic nephropathy by mitigating oxidative stress and inflammation, and upregulating Nrf2/HO-1 signaling in diabetic rats
| Autor: | Samar A. Antar, Walied Abdo, Reda S. Taha, Amira E. Farage, Laila E. El-Moselhy, Mohamed E. Amer, Ahmed S. Abdel Monsef, Amer M. Abdel Hamid, Emadeldin M. Kamel, Ahmad F. Ahmeda, Ayman M. Mahmoud |
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| Rok vydání: | 2021 |
| Předmět: |
Inflammation
Male NF-E2-Related Factor 2 General Medicine Kidney General Biochemistry Genetics and Molecular Biology Streptozocin Diabetes Mellitus Experimental Rats Molecular Docking Simulation Rats Sprague-Dawley Oxidative Stress Heme Oxygenase (Decyclizing) Animals Diabetic Nephropathies Telmisartan General Pharmacology Toxicology and Pharmaceutics Signal Transduction |
| Zdroj: | Life sciences. 291 |
| ISSN: | 1879-0631 |
| Popis: | Diabetic nephropathy (DN) is a serious complication of diabetes and can lead to renal failure. Telmisartan (TEL) is an approved angiotensin II type 1 receptor blocker for the treatment of hypertension and possesses nephroprotective efficacy. The study investigated the beneficial effect of TEL on renal oxidative stress, inflammatory response, and apoptosis in type 1 diabetic rats, pointing to the possible role of Nrf2/HO-1 signaling. Diabetes was induced by streptozotocin (STZ), and TEL (5 and 10 mg/kg) was supplement for 8 weeks. TEL ameliorated hyperglycemia, prevented body weight loss and kidney hypertrophy, decreased serum creatinine and urea, and prevented histopathological alterations in diabetic rats. Malondialdehyde (MDA), nitric oxide (NO), NF-κB p65 and TNF-α were increased, whereas GSH, SOD and Bcl-2 were decreased in the kidney of diabetic rats. Treatment with TEL ameliorated oxidative stress, suppressed NF-κB p65 and TNF-α, and boosted cellular antioxidant defenses and Bcl-2. TEL upregulated Nrf2 and HO-1 in the kidney of both normal and diabetic rats. In addition, TEL downregulated VEGF and MMP-9 in the kidney of diabetic rats. In silico molecular docking simulations revealed the potent binding affinity of TEL to NF-κB, MMP-9, Keap1 and HO-1. In conclusion, TEL attenuates DN by ameliorating hyperglycemia, oxidative stress, inflammation, apoptosis and angiogenesis and upregulation of Nrf2/HO-1 signaling. |
| Databáze: | OpenAIRE |
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