Modulation of hepatic microsomal triglyceride transfer protein (MTP) induced by S-nitroso-N-acetylcysteine in ob/ob mice

Oliveira, Cláudia Pinto Marques Souza de; Alves, Venâncio Avancini Ferreira; Lima, Verônica Castro; Stefano, José Tadeu; Debbas, Victor; Sá, Sandra Valéria; Wakamatsu, Alda; Corrêa-Giannella, Maria Lúcia; Mello, Evandro Sobroza de; Havaki, Sofia; Tiniakos, Dina; Marinos, Evangelos; Oliveira, Marcelo Ganzarolli de; Giannella-Neto, Daniel; Laurindo, Francisco Rafael Martins; Caldwell, Stephen H.; Carrilho, Flair José

doi:10.1016/j.bcp.2007.04.013

Cited by 14 publications

(7 citation statements)

References 31 publications

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“…Using the same ob/ob mouse model of NAFLD, others showed that, NAC at 7.5 mM or SNAC at 1.4 µmol/kg for 4 weeks could reduce liver steatosis. This was shown to occur in part by lowering the markers of inflammation and lipid oxidation, which led to improved mitochondrial function, oxidative phosphorylation and intracellular antioxidant responses [9,[66][67][68][69].…”

Section: Impact Of Nac On Lipid Accumulation Oxidative Stress and Inmentioning

confidence: 99%

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

et al. 2020

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Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential.

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Section: Impact Of Nac On Lipid Accumulation Oxidative Stress and Inmentioning

confidence: 99%

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

et al. 2020

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“…The administration of SNAC was associated with a reduction in the histological criteria of experimental NASH, concomitant with a reduction in MTP protein expression measured by both Western blot and immunohistochemistry, an increase of MTP mRNA content and an altered intracellular distribution of MTP. The decrease of MTP expression by SNAC seems to occur secondary to other beneficial effects associated with SNAC, since it has been previously demonstrated that this nitric oxide donor elicits downregulation of genes belonging to FA biosynthesis pathways, possibly resulting in the prevention of FA accumulation [39]. The finding that this compound modulates MTP expression opens new perspectives in the study of the effects of SNAC not only in the liver, but also in the small intestine, where MTP plays a pivotal role in lipid absorption.…”

Section: Mtp As a Therapeutic Targetmentioning

confidence: 99%

Microsomal triglyceride transfer protein and nonalcoholic fatty liver disease

Pereira

Stefano

Oliveira

2011

Expert Review of Gastroenterology & Hepatology

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Nonalcoholic fatty liver disease is currently one of the most common forms of liver disease, covering cases from simple steatosis without inflammation, to cases of steatohepatitis and fibrosis, and may lead to liver cirrhosis and hepatocellular carcinoma. The pathophysiology of nonalcoholic fatty liver disease is based on multiple events; changes in the secretion of lipoproteins can lead to steatosis. Liver lipid secretion is mediated by apoB100 and microsomal triglyceride transfer protein (MTP). The pharmacological suppression of MTP is suggested as a possible treatment for hyperlipidemia, although the upregulation of this protein can be a treatment for nonalcoholic steatohepatitis.

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“…[1][2][3][4][5][6] In these cases, it is assumed that free radicals which normally play an essential role in metabolic processes, are released from the active site of enzymes, triggering a cascade of deleterious effects on cells. 7 These effects involve the interaction of free radicals with metal or organic redox centers and the promotion of irreversible oxidation reactions beyond the normal catalytic cycles.…”

Section: Introductionmentioning

confidence: 99%

“…This protective effect has already been observed in model lipid systems, 14,15 low-density lipoproteins (LDL) [16][17][18] and cells 19,20 29 As an alternative strategy, compounds that act as NO donors could be administrated as exogenous NO sources, as already demonstrated for the treatment of hepatic steatosis via oral administration of the S-nitrosothiol (RSNO) S-nitroso-Nacetylcysteine (SNAC). [3][4][5][6] RSNOs are peptides or proteins carrying the S-NO moiety and were shown to occur in the plasma and cells of mammals where they have the same physiological functions of free • NO like vasodilation, 30,31 inhibition of platelet activation and aggregation 32,33 and post-translational modification of protein function. 34,35 S-nitrosoglutathione (GSNO), S-nitrosoalbumin and S-nitrosohemoglobin, for example, have been considered to be • NO carriers and donors in humans and are the focus of several studies both in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 99%

In vitro inhibition of linoleic acid peroxidation by primary S-nitrosothiols

Simplicio¹,

Seabra²,

Souza³

et al. 2010

J. Braz. Chem. Soc.

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Nitric oxide ( • NO) is an effective chain-breaking antioxidant in the inhibition of lipid peroxidation and circulates in vivo mainly as primary S-nitrosothiols (RSNOs). In this work, the in vitro peroxidation of linoleic acid-SDS comicelles (LA-SDS) catalyzed by soybean lipoxygenase (SLO) and FeII ions was monitored in the presence and absence of three primary RSNOs: S-nitrosocysteine, S-nitroso-N-acetylcysteyne and S-nitrosoglutathione. Kinetic measurements based on the formation of conjugated double bonds and fluorescent oxidized LA-lysine adducts, showed that RSNOs are more potent antioxidants than their corresponding free thiols (RSHs) in equimolar conditions. These results are consistent with the blocking of LA-SDS peroxidation by RSNOs through the inactivation of peroxyl/alkoxyl (LOO • /LO • ) radicals, leading to nitrogencontaining products of oxidized LA, which release free • NO. These results indicate that endogenous RSNOs may play a major role in the blocking of lipid peroxidation in vivo, through the primary inactivation of alkoxyl/peroxyl radicals and also of preformed lipid hydroperoxides.

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Modulation of hepatic microsomal triglyceride transfer protein (MTP) induced by S-nitroso-N-acetylcysteine in ob/ob mice

Cited by 14 publications

References 31 publications

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

Microsomal triglyceride transfer protein and nonalcoholic fatty liver disease

In vitro inhibition of linoleic acid peroxidation by primary S-nitrosothiols

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