Enalapril Attenuates Oxidative Stress in Diabetic Rats

Abstract

Abstract-Oxidative stress is involved in both the pathogenesis and complications of diabetes. ACE inhibitors can slow the progression of cardiac and renal impairments related to diabetes. The effect of enalapril treatment on oxidative stress and tissue injury was studied in hearts, kidneys, and livers from streptozotocin-induced diabetic rats. Twenty-four rats were divided into the following groups: streptozotocin (65 mg/kg, single intraperitoneal dose), streptozotocinϩenalapril (20 mg enalapril/L drinking water), and control (intraperitoneal saline). Seven months after streptozotocin injection, organs were studied by light microscopy and collagen III immunolabeling. Tissue lesions and collagen labeling were graded by a semiquantitative score (0 to 4). Total glutathione content, glutathione redox status (reduced/oxidized glutathione), antioxidant enzyme activities, protein-associated sulfhydryls, thiobarbituric acid-reactive substances, and fluorescent chromolipids were determined in tissue homogenates. Glycemia was higher in both the streptozotocin and streptozotocinϩenalapril groups relative to the control group. In the streptozotocin group, creatinine clearance and body weight were lower, and systolic blood pressure and urinary albumin excretion were higher than in the streptozotocinϩenalapril and control groups. Heart, kidney, and liver lesion/labeling scores were significantly higher in the streptozotocin group compared with the streptozotocinϩenalapril and control groups. Kidney and liver total glutathione was lower in the streptozotocin group relative to the control group (PϽ0.05). Enalapril treatment significantly attenuated the reduction of total glutathione. In the heart, kidney, and liver, both glutathione and proteins were relatively more oxidized in the streptozotocin group relative to the control group (PϽ0.05). Protein and glutathione oxidation were attenuated in the streptozotocinϩenalapril group in the 3 tissues studied (PϽ0.05). Enalapril treatment attenuated the oxidation of lipids in the heart and kidney (PϽ0.05). Tissue fibrosis scores were inversely correlated with (1) both total glutathione and reduced/oxidized glutathione in heart, kidney, and liver and (2) glutathione reductase activity in the kidney. These results suggest that in streptozotocin-induced diabetic rats, the protective action of enalapril might be mediated, at least in part, by its effect on tissue oxidant/antioxidant status.

ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats

“…Moreover, the ACEI-induced increase in GPx activity is significantly blunted by coadministration of the B2R antagonist. Such stimulation or protection of anti-oxidant systems by ACEI inhibitors has been previously documented in various tissues in aging mice and rats (9,11,13), in hemodialysis patients (10), and in diabetic rats (12).…”

Losartan improves impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type 1 diabetic rats

“…Mechanisms that account for the effects of ACE inhibitors and AT1R antagonists on vascular dysfunction are not clear but have been reported to be related to effects on insulin sensitivity (Torlone et al, 1993), potentiating the actions of bradykinin (Cachofeiro et al, 1992), an increase in NOS activity (Gonzalez Bosc et al, 2001;, and/ or by inhibiting the influence of angiotensin II on oxidative stress (de Cavanagh et al, 2001;Welch and Wilcox, 2001). Support for this latter concept can be found in studies that have shown that stimulation of vascular cells with angiotensin II increases the activity of NAD(P)H oxidase, increases the expression of p47phox and stimulates the production of superoxide anion (Fukui et al, 1997;Griendling et al, 1994;Griendling et al, 2000;Landmesser et al, 2002;.…”

Effect of levetiracetam on hepatic fibrosis in diabetic rats

“…[8] In another study by using angiotensin converting enzyme inhibitor to protect liver damage in STZ-induced diabetic rats, they had shown the negative correlation between liver tissue fibrosis and glutathione related antioxidant defenses. [9] As a result we showed that when compared with histological investigation, real-time elastography is a reliable imaging technique for detecting hepatic fibrosis. Taken together the mechanism of action of LEV and pathogenesis of diabetic liver injury, LEV has potential as a treatment for diabetic liver injury and hepatic fibrosis and can be a good candidate among new treatment options.…”

“…Our result was consistent with the other studies and showed that type 2 DM and hyperglycemia are major risk factors for diabetic hepatic injury. [9] Pathogenesis of diabetic liver injury comprises two steps. The first step is thought to be insulin resistance increasing the transport of fatty acids from adipose tissue to the liver and causes accumulation of fat in the hepatocytes.…”

“…In the previous studies they have shown that different types of antioxidants could attenuate the complications of diabetes including fatty liver diseases and fibrosis. [7][8][9] Levetiracetam (LEV) is a commonly used antiepileptic drug that acts as a histone deacetylase inhibitor and an inhibitor of highvoltage activated N-type calcium channels. The recent evidence shows that the drug has antiinflammatory and antioxidative effects.…”