氧化应激
糖尿病肾病
替米沙坦
医学
糖尿病
内分泌学
肾
内科学
丙二醛
链脲佐菌素
肾病
下调和上调
药理学
一氧化氮
化学
生物化学
血压
基因
作者
Samar A. Antar,Walied Abdo,Reda Taha,Amira El-Sayed farage,Laila E. El-Moselhy,Mohamed Amer,Ahmed S. Abdmonsef,Amer M. Abdel Hamid,Emadeldin M. Kamel,Ahmad Ahmeda,Ayman M. Mahmoud
出处
期刊:Life Sciences
[Elsevier]
日期:2021-12-01
卷期号:291: 120260-120260
被引量:17
标识
DOI:10.1016/j.lfs.2021.120260
摘要
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.
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