期刊
LIFE SCIENCES
卷 291, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.120260
关键词
Hyperglycemia; Oxidative stress; Angiotensin II receptor blockers; Inflammation; Nrf2; Telmisartan
This study found that telmisartan has a protective effect on renal damage in diabetic rats, reducing hyperglycemia, oxidative stress, inflammation, apoptosis, and angiogenesis. It achieves this protective effect by upregulating the Nrf2/HO-1 signaling pathway.
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-kappa B p65 and TNF-alpha were increased, whereas GSH, SOD and Bcl-2 were decreased in the kidney of diabetic rats. Treatment with TEL ameliorated oxidative stress, suppressed NF-kappa B p65 and TNF-alpha, 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-kappa B, 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.
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