Modulation of cardiac and aortic peroxisome proliferator-activated receptor-gamma expression by oxidative stress in chronically glucose-fed rats.
ABSTRACT The aim of the present study was to examine the chronic effects of alpha-lipoic acid on proliferator peroxisome activated receptors-gamma (PPAR-gamma) and PPAR-alpha expressions in cardiovascular tissues of chronically hypertensive insulinoresistant rats. We have also evaluated the chronic effects of high levels of insulin, glucose, or both on superoxide anion (O(2)(-)) production in aortic smooth muscle cells (SMCs) in the presence or in absence of pioglitazone, a PPAR-gamma agonist.
The PPAR-gamma and PPAR-alpha expressions were measured by Western blot. The oxidative stress was evaluated by measuring the O(2)(-) production using the lucigenin method.
Increases in blood pressure, in aortic O(2)(-) production, in glucose or insulin levels, and in insulin resistance, as well as the decrease in PPAR-gamma protein levels in aorta and heart tissues were prevented or attenuated in glucose-treated rats fed with lipoic acid. Chronic treatment with pioglitazone prevented the marked increase in O(2)(-) production in cultured SMCs chronically treated with high insulin combined or not with high glucose levels.
The combined therapy with the antioxidant alpha-lipoic acid restored PPAR-gamma levels in cardiovascular tissues and attenuated or prevented the development of insulin resistance and hypertension in chronically glucose-fed rats. Moreover, the finding that pioglitazone was also efficient in preventing the increase in oxidative stress in SMCs treated with high insulin combined with high glucose concentrations supports the hypothesis that the activation of PPAR-gamma activity can counteract the oxidative stress that seems to be implicated in the development of hypertension and insulin resistance.
- SourceAvailable from: Zhaohui Pei[Show abstract] [Hide abstract]
ABSTRACT: The aim of the present study was to examine the effects of acute infrasound exposure on oxidative damage and investigate the underlying mechanisms in rat cardiomyocytes. Neonatal rat cardiomyocytes were cultured and exposed to infrasound for several days. In the study, the expression of CAT, GPx, SOD1, and SOD2 and their activities in rat cardiomyocytes in infrasound exposure groups were significantly decreased compared to those in the various time controls, along with significantly higher levels of O2 (-) and H2O2. Decreased cardiac cell viability was not observed in various time controls. A significant reduction in cardiac cell viability was observed in the infrasound group compared to the control, while significantly increased cardiac cell viability was observed in the infrasound exposure and rosiglitazone pretreatment group. Compared to the control, rosiglitazone significantly upregulated CAT, GPx, SOD1, and SOD2 expression and their activities in rat cardiomyocytes exposed to infrasound, while the levels of O2 (-) or H2O2 were significantly decreased. A potential link between a significant downregulation of PPAR-γ expression in rat cardiomyocytes in the infrasound group was compared to the control and infrasound-induced oxidative stress. These findings indicate that infrasound can induce oxidative damage in rat cardiomyocytes by inactivating PPAR-γ.Cardiovascular toxicology 05/2013; 13(4). DOI:10.1007/s12012-013-9211-5 · 2.06 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: ABSTRACT In the present study, the antioxidant activities of Hibiscus rosa-sinensis Linn. flower petals treatment for 4 weeks were screened in 10% D-glucose feeding in rats. Experimental rats were treated with 10% D-glucose solution to drink orally. H. rosa-sinensis flower petals (1,000 mg/kg of body weight) were mixed with normal chow diet and administrated for 4 weeks as preventive and curative effects. An appreciable decrease in peroxidation product viz. malondialdehyde is observed in heart tissues of H. rosa-sinensis treated in 10% D-glucose-fed rats. The decreased activities of key antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and nonenzymatic antioxidants such as glutathione, vitamin E and vitamin C in 10% D-glucose-fed rats were brought back to near-normal range upon H. rosa-sinensis flower petals treatment. In conclusion, H. rosa-sinensis exhibited preventive and curative effects in 10% D-glucose-induced oxidative stress in rat heart tissues. PRACTICAL APPLICATIONS Acute oral glucose feeding causes oxidative stress and functional decline in heart of healthy subjects. Hibiscus rosa-sinensis is one of the medicinal plants that have attracted particular attention in folk medicine because of its widespread health use around the world. This study aims to enlighten the beneficial effects of H. rosa-sinensis in 10% glucose feeding-induced heart damage. These results led to development of a new phytomedicinal product with antioxidant activity to reduce heart diseases.Journal of Food Biochemistry 06/2011; 35(3). DOI:10.1111/j.1745-4514.2010.00417.x · 0.85 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non-diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR-γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg(-1) ). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg(-1) day(-1) , per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non-enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S-transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR-γ agonists in human application for protecting against drugs-induced nephrotoxicity. Copyright © 2012 John Wiley & Sons, Ltd.Journal of Applied Toxicology 01/2014; 34(1). DOI:10.1002/jat.2818 · 3.17 Impact Factor