Comparative effects of Aliskiren and Telmisartan in high fructose diet-induced metabolic syndrome in rats

Oxidative stress is one of the mechanisms involved in the acute carbon tetrachloride (CCl4)-induced hepatotoxicity. Since 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, known as tempol, has powerful antioxidant properties, we investigated its potential hepatoprotective effects and the underlying mechanisms that may add further benefits for its clinical usefulness using an acute model of CCl4-induced hepatotoxicity. One hour after CCl4 induction of acute hepatotoxicity, mice were treated with a daily dose of 20 mg/kg/day tempol for 3 days. It was found that treatment of animals with tempol significantly negated the pathological changes in liver function parameters as well as histology induced by CCl4. In addition, tempol significantly ameliorated CCl4-induced lipid peroxidation and GSH depletion, and improved catalase activity. Furthermore, tempol alleviated the inflammation induced by CCl4 as indicated by reducing the liver expression level of nuclear factor-kappa B (NF-κB) and tumor necrosis factor-α (TNF-α). Finally, tempol significantly reduced expression level of the B-cell lymphoma-2 protein (Bcl-2) and active caspase-3 which are known markers of apoptosis. In conclusion, the present study provides important evidences for the promising hepatoprotective effects of tempol that can be explained by amelioration of oxidative stress mainly through replenishment of GSH, restoration of antioxidant enzyme activities, and reduction of lipid peroxides alongside its anti-inflammatory properties.

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“…Liver homogenate was prepared as previously described [31]. GSH content was determined using Ellman's reagent [32].…”

Section: Determination Of Hepatic Glutathione (Gsh) and Catalase (Catmentioning

confidence: 99%

Experimental evidence for the therapeutic potential of tempol in the treatment of acute liver injury

et al. 2015

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“…A direct renin inhibitor, aliskiren, has been extensively applied in rats with spontaneous hypertension [10] and can block Ang II production [16]. Recently reported, aliskiren have the beneficial effects on improving insulin sensitivity, hepatic steatosis, peripheral fat mass, and oxidative stress markers in rodents with metabolic syndrome [17, 18]. Further, the effects of renin inhibition on visceral adiposity in metabolic syndrome are currently under investigation.…”

Section: Introductionmentioning

confidence: 99%

Renin inhibition improves metabolic syndrome, and reduces angiotensin II levels and oxidative stress in visceral fat tissues in fructose-fed rats

et al. 2017

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Renin–angiotensin system in visceral fat plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats. However, the effects of renin inhibition on visceral adiposity in metabolic syndrome are not fully investigated. We investigated the effects of renin inhibition on visceral adiposity in fructose-fed rats. Male Wistar–Kyoto rats were divided into 4 groups for 8-week experiments: Group Con (standard chow diet), Group Fru (high-fructose diet; 60% fructose), Group FruA (high-fructose diet and concurrent aliskiren treatment; 100 mg/kg body weight [BW] per day), and Group FruB (high-fructose diet and subsequent, i.e. 4 weeks after initiating high-fructose feeding, aliskiren treatment; 100 mg/kg BW per day). The high-fructose diet induced metabolic syndrome, increased visceral fat weights and adipocyte sizes, and augmented angiotensin II (Ang II), NADPH oxidase (NOX) isoforms expressions, oxidative stress, and dysregulated production of adipocytokines from visceral adipose tissues. Concurrent and subsequent aliskiren administration ameliorated metabolic syndrome, dysregulated adipocytokines, and visceral adiposity in high fructose-fed hypertensive rats, and was associated with reducing Ang II levels, NOX isoforms expressions and oxidative stress in visceral fat tissues. Therefore, this study demonstrates renin inhibition could improve metabolic syndrome, and reduce Ang II levels and oxidative stress in visceral fat tissue in fructose-fed rats, and suggests that visceral adipose Ang II plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats.

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“…Metabolic syndrome (MS) is a worldwide problem that is currently receiving much exploration, both in experimental animals and in the clinic (Alam et al 2016;Liu et al 2016;Rabie et al 2015;Vu et al 2016). MS is a combination of medical disorders which increases the risk of cardiovascular disease and diabetes (Benson et al 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Either inhibition of RAS or Block of angiotensin receptors is thought to ameliorate MS criteria (Rabie et al 2015), may be through improvement of insulin sensitivity independent of changes in blood pressure (Mori et al 2007), prevention of weight gain in addition (de Kloet et al 2010), reduction in liver injury, attenuation of oxidative stress parameters and hepatic expressions of inflammatory and fibrotic markers (Rabie et al 2015) D r a f t 4 Telmisartan is an orally active antagonist of angiotensin II type I receptors (AT 1 ), it has the highest affinity for the AT 1 receptors among the available AT1 antagonists (Kakuta et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Effects of telmisartan and pioglitazone on high fructose induced metabolic syndrome in rats

Shahataa

Mostafa‐Hedeab

Ali

et al. 2016

Can. J. Physiol. Pharmacol.

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Comparative effects of Aliskiren and Telmisartan in high fructose diet-induced metabolic syndrome in rats

Cited by 32 publications

References 49 publications

Experimental evidence for the therapeutic potential of tempol in the treatment of acute liver injury

Experimental evidence for the therapeutic potential of tempol in the treatment of acute liver injury

Renin inhibition improves metabolic syndrome, and reduces angiotensin II levels and oxidative stress in visceral fat tissues in fructose-fed rats

Effects of telmisartan and pioglitazone on high fructose induced metabolic syndrome in rats

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