Simvastatin Ameliorates Diabetic Cardiomyopathy by Attenuating Oxidative Stress and Inflammation in Rats

被引：129

作者：

Al-Rasheed, Nawal M. ^{[1
,2
]}

Al-Rasheed, Nouf M. ^{[1
]}

Hasan, Iman H. ^{[1
]}

Al-Amin, Maha A. ^{[1
]}

Al-Ajmi, Hanaa N. ^{[1
]}

Mohamad, Raeesa A. ^{[3
]}

Mahmoud, Ayman M. ^{[4
,5
,6
]}

机构：

[1] King Saud Univ, Dept Pharmacol & Toxicol, Coll Pharm, Riyadh, Saudi Arabia

[2] Princess Nourah Bint Abdulrahman Univ, Dept Pharmaceut Sci, Coll Pharm, Riyadh, Saudi Arabia

[3] King Saud Univ, Dept Anat, Coll Med, Riyadh, Saudi Arabia

[4] Beni Suef Univ, Div Physiol, Dept Zool, Fac Sci, Bani Suwayf, Egypt

[5] Charite Univ Med Berlin, Dept Endocrinol Diabet & Nutr, Berlin, Germany

[6] Charite Univ Med Berlin, Dept Endocrinol Diabet & Nutr, CCR, Berlin, Germany

来源：

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY | 2017年 / 2017卷

关键词：

NITRIC-OXIDE SYNTHASE; CARDIAC-HYPERTROPHY; VENTRICULAR DYSFUNCTION; SUPEROXIDE-PRODUCTION; INSULIN-RESISTANCE; NAD(P)H OXIDASE; BLOOD-PRESSURE; NO-REFLOW; IN-VITRO; MECHANISMS;

D O I：

10.1155/2017/1092015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Simvastatin is a lipid-lowering agent used to treat hypercholesterolemia and to reduce the risk of heart disease. This study scrutinized the beneficial effects of simvastatin on experimental diabetic cardiomyopathy (DCM), pointing to the role of hyperglycemia-induced oxidative stress and inflammation. Diabetes was induced by intraperitoneal injection of streptozotocin and both control and diabetic rats received simvastatin for 90 days. Diabetic rats showed significant cardiac hypertrophy, body weight loss, hyperglycemia, and hyperlipidemia. Serum creatine kinase MB (CK-MB) and troponin I showed a significant increase in diabetic rats. Simvastatin significantly improved body weight, attenuated hyperglycemia and hyperlipidemia, and ameliorated CK-MB and troponin I. Simvastatin prevented histological alterations and deposition of collagen in the heart of diabetic animals. Lipid peroxidation and nitric oxide were increased in the heart of diabetic rats whereas antioxidant defenses were decreased. These alterations were significantly reversed by simvastatin. In addition, simvastatin decreased serum inflammatory mediators and expression of NF-kappa B in the diabetic heart. Cardiac caspase-3 was increased in the diabetic heart and decreased following treatment with simvastatin. In conclusion, our results suggest that simvastatin alleviates DCM by attenuating hyperglycemia/hyperlipidemia-induced oxidative stress, inflammation, and apoptosis.

引用

页数：13

共 73 条

[1] Sitagliptin attenuates cardiomyopathy by modulating the JAK/STAT signaling pathway in experimental diabetic rats [J].

Al-Rasheed, Nouf M. ;

Al-Rasheed, Nawal M. ;

Hasan, Iman H. ;

Al-Amin, Maha A. ;

Al-Ajmi, Hanaa N. ;

Mahmoud, Ayman M. .

DRUG DESIGN DEVELOPMENT AND THERAPY, 2016, 10 :2095-2107

[2] Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway [J].

Al-Rasheed, Nouf M. ;

Al-Oteibi, Maha M. ;

Al-Manee, Reem Z. ;

Al-Shareef, Sarah A. ;

Al-Rasheed, Nawal M. ;

Hasan, Iman H. ;

Mohamad, Raeesa A. ;

Mahmoud, Ayman M. .

DRUG DESIGN DEVELOPMENT AND THERAPY, 2015, 9 :3217-3229

[3]

ALLAIN CC, 1974, CLIN CHEM, V20, P470

[4] NF-κB, Inflammation, and Metabolic Disease [J].

Baker, Rebecca G. ;

Hayden, Matthew S. ;

Ghosh, Sankar .

CELL METABOLISM, 2011, 13 (01) :11-22

[5] Heart failure prevalence, incidence, and mortality in the elderly with diabetes [J].

Bertoni, AG ;

Hundley, WG ;

Massing, MW ;

Bonds, DE ;

Burke, GL ;

Goff, DC .

DIABETES CARE, 2004, 27 (03) :699-703

[6]

BEUTLER E, 1963, J LAB CLIN MED, V61, P882

[7] Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update [J].

Bhattacharjee, Niloy ;

Barma, Sujata ;

Konwar, Nandita ;

Dewanjee, Saikat ;

Manna, Prasenjit .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2016, 791 :8-24

[8] Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity [J].

Boudina, S ;

Sena, S ;

O'Neill, BT ;

Tathireddy, P ;

Young, ME ;

Abel, ED .

CIRCULATION, 2005, 112 (17) :2686-2695

[9] Diabetic cardiomyopathy revisited [J].

Boudina, Sihem ;

Abel, E. Dale .

CIRCULATION, 2007, 115 (25) :3213-3223

[10] Diabetic cardiomyopathy, causes and effects [J].

Boudina, Sihem ;

Abel, Evan Dale .

REVIEWS IN ENDOCRINE & METABOLIC DISORDERS, 2010, 11 (01) :31-39

← 1 2 3 4 5 6 7 8 →