Effects of altered hepatic lipid metabolism on regulation of hepatic iNOS

Stanimirović, Julijana; Obradović, Milan; Zafirović, Sonja; Resanović, Ivana; Bogdanovic, Nikola; Gluvić, Zoran; Mousa, Shaker A.; Isenović, Esma R.

doi:10.2217/clp.15.8

Cited by 10 publications

(10 citation statements)

References 93 publications

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“…This difference makes CAT ideal for consuming toxic levels of H 2 O 2 while allowing the GSH and SOD to manipulate the lower sub-toxic amounts of H 2 O 2 . Besides, the decrease occurred in the GSH would lower D r a f t -19-resulting in elevation of NO production (Stanimirovic et al 2015). Provoking inflammatory response upregulates inflammatory cytokines, and leads to release of NO from macrophages as a defense response (Reddy and Rao 2006).…”

Section: Febuxostat Anti-oxidant Effect Protects Against Hfd-inducedmentioning

confidence: 99%

Effect of febuxostat on biochemical parameters of hyperlipidemia induced by a high-fat diet in rabbits

Heikal

Shaaban

Elkashef

et al. 2019

Can. J. Physiol. Pharmacol.

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Objective-To test the potential anti-oxidant and anti-inflammatory effects of febuxostat and/or stopping high-fat diet on the biochemical parameters of high fat diet-induced hyperlipidemic rabbits.Background-Febuxostat, a highly potent xanthine oxidase inhibitor with antioxidant effect, inhibits elevated xanthine oxidase, leading to reduction of reactive oxygen species (ROS) and oxidative stress, the main causes of vascular inflammation in hyperlipidemia. Methods-Male NewZealand rabbits were distributed in three groups: normal control (NC) fed standard chow for 12 weeks; the other two groups fed high-fat diet (HFD) with 1% cholesterol for 8 weeks, and then shifted to standard chow for 4 weeks. During the last 4 weeks; the (HFD) group received vehicle 0.5% carboxymethyl cellulose (CMC), while the treated (FX) group received febuxostat in doses (2 mg/kg/day p.o.). Results-Febuxostatsignificantly lowered "bad" cholesterol. Febuxostat also displayed a potent anti-inflammatory and antioxidant activity by decreasing serum levels of lipid peroxidation index, pro-inflammatory cytokines and enhancing antioxidant-enzyme activity. Stopping hyperlipidemic diet in HFD group didn't show improvement. Conclusions-These findings indicate antioxidant and anti-inflammatory effects of febuxostat that may be common mechanisms of the anti-hyperlipidemic effect of this drug. Stopping hyperlipidemic diet without treatment is not sufficient once injury occurred.

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Section: Febuxostat Anti-oxidant Effect Protects Against Hfd-inducedmentioning

confidence: 99%

Effect of febuxostat on biochemical parameters of hyperlipidemia induced by a high-fat diet in rabbits

Heikal

Shaaban

Elkashef

et al. 2019

Can. J. Physiol. Pharmacol.

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“…However, overexpression of iNOS is hypothesized to be involved in the development of IR and CVD, and may be the key link between obesity related metabolic disorders and inflammation [17,18]. In dietary and genetic models of obesity, excessive accumulation of lipids can induce iNOS expression and nitric oxide (NO) production in metabolic tissues [17,19,20].…”

Section: Inducible Nitric Oxide Synthase (Inos) Is An Important Inflamentioning

confidence: 99%

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Jovanović

Sudar-Milovanović

Obradović

et al. 2017

CVP

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Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular (CV) disease. Several studies have reported that oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. In the present study, female Wistar rats were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. Gene and protein expression of iNOS were measured in heart tissue. HF diet-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p<0.05), iNOS protein level by 248% (p<0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p<0.01) in HF diet-fed rats. Expression of the p50 subunit of nuclear factor-κB (NFκB-p50) in heart lysate was increased by 77% (p<0.01) in HF diet-fed rats.Expression and phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2) in control and HF diet-fed rats were also examined. Expression of Akt and ERK1/2 were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2/ in HF-fed rats.Estrogen receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were examined and shown to be significantly reduced in HF diet-fed rats. Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NFκB-p50 proteins. Decreased levels of oestradiol and ERα protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.Key words: cardioprotection, cardiovascular disease, oestradiol, inducible nitric oxide synthase, obesity Abbreviations: Akt, protein kinase B; CD36, cluster of differentiation 36; CHD, coronary heart disease; CV, cardiovascular; CVD, cardiovascular disease; DMT2, diabetes mellitus type 2; ERα, oestrogen receptor-α; ERs, oestrogen receptors; ERK1/2, extracellular signalregulated kinases 1/2; FFA, free fatty acids; HF, high fat; HOMA-IR, HOMA-index of insulin resistance; HOMA-β, HOMA-index of β-cell function; IκB, inhibitor of NFκB; iNOS, inducible nitric oxide synthase; IR, insulin resistance; NFκB-p50, the p50 subunit of nuclear factor-κB; TES, N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid; TG, triglycerides VSMCs, vascular smooth muscle cells.

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“…Endogenously, NO is released as a product during conversion of the amino acid Larginine (L-arg) to L-citrulline in a reaction mediated by NOS (Stanimirovic et al 2015, SudarMilovanovic et al 2015. The primary source of NO generation in the vascular system is endothelial NOS (Rhodes et al 1995, Kypreos et al 2014).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

17β-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats

Zafirović

Obradović

Sudar-Milovanović

et al. 2017

Molecular and Cellular Endocrinology

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Please cite this article as: Zafirovic, S., Obradovic, M., Sudar-Milovanovic, E., Jovanovic, A., Stanimirovic, J., Stewart, A.J., Pitt, S.J., Isenovic, E.R., 17β-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats, Molecular and Cellular Endocrinology (2017), doi: 10.1016/j.mce.2017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe aim of this study was to investigate the in vivo effects of estradiol (E 2 ) on myocardial metabolism and inducible nitric oxide synthase (iNOS) expression/activity in obese rats. MaleWistar rats were fed with a normal or a high fat (HF) diet (42% fat) for 10 weeks. Half of the HF fed rats were treated with a single dose of E 2 while the other half were placebo-treated. 24h after treatment animals were sacrificed. E 2 reduced cardiac free fatty acid (FFA Akt, protein kinase B; AS160, Akt substrate of 160 kDa; CD36, fatty acid transporters; E 2 ,

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Effects of altered hepatic lipid metabolism on regulation of hepatic iNOS

Cited by 10 publications

References 93 publications

Effect of febuxostat on biochemical parameters of hyperlipidemia induced by a high-fat diet in rabbits

Effect of febuxostat on biochemical parameters of hyperlipidemia induced by a high-fat diet in rabbits

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

17β-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats

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