Telmisartan attenuates diabetic nephropathy by mitigating oxidative stress and inflammation, and upregulating Nrf2/HO-1 signaling in diabetic rats

被引：53

作者：

Antar, Samar A. ^{[1
]}

Abdo, Walied ^{[2
]}

Taha, Reda S. ^{[3
]}

Farage, Amira E. ^{[4
]}

El-Moselhy, Laila E. ^{[5
]}

Amer, Mohamed E. ^{[5
]}

Monsef, Ahmed S. Abdel ^{[6
]}

Hamid, Amer M. Abdel ^{[7
]}

Kamel, Emadeldin M. ^{[8
]}

Ahmeda, Ahmad F. ^{[9
,10
]}

Mahmoud, Ayman M. ^{[11
]}

机构：

[1] Horus Univ, Fac Pharm, Dept Pharmacol & Biochem, Dumyat Al Jadidah, Egypt

[2] Kafrelsheikh Univ, Fac Vet Med, Dept Pathol, Kafrelsheikh, Egypt

[3] Al Azhar Univ, Fac Med, Dept Anat, Dumyat, Egypt

[4] Kafrelsheikh Univ, Fac Med, Dept Anat & Embryol, Kafrelsheikh, Egypt

[5] Al Azhar Univ, Fac Med, Dept Histol, Dumyat, Egypt

[6] Al Azhar Univ, Fac Med, Dept Physiol, Dumyat, Egypt

[7] Al Azhar Univ, Fac Med, Dept Med Biochem, Dumyat, Egypt

[8] Beni Suef Univ, Fac Sci, Chem Dept, Bani Suwayf, Egypt

[9] Ajman Univ, Coll Med, Dept Basic Med Sci, Ajman, U Arab Emirates

[10] Ajman Univ, Ctr Med & Bioallied Hlth Sci Res, Ajman, U Arab Emirates

[11] Beni Suef Univ, Fac Sci, Zool Dept, Physiol Div, Salah Salim St, Bani Suwayf 62514, Egypt

来源：

LIFE SCIENCES | 2022年 / 291卷

关键词：

Hyperglycemia; Oxidative stress; Angiotensin II receptor blockers; Inflammation; Nrf2; Telmisartan; ACTIVATED RECEPTOR-GAMMA; STREPTOZOTOCIN; COMPLICATIONS; APOPTOSIS; CARDIOMYOPATHY; MODULATION; PREVENTION; EXPRESSION; DISEASE; CELLS;

D O I：

10.1016/j.lfs.2021.120260

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

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-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.

引用

页数：13

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