N-Acetyl-l-Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats

Villagarcía, Hernán Gonzalo; Castro, M.; Arbeláez, Luisa Fernanda González; Schinella, Guillermo Raúl; Massa, María Laura; Spinedi, Eduardo; Francini, Flavio

doi:10.1016/j.lfs.2018.03.008

Cited by 14 publications

(6 citation statements)

References 66 publications

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“…And ROS in turn promotes the activation of PKCδ, IKK-β, and c-Jun N-terminal kinase (JNK) to exacerbate oxidative stress. In line with previous researches, antioxidants like N-acetyl-l-cysteine and taurine can significantly prevent hepatic insulin resistance through suppression of excessive oxidative stress in rats (Guo-Guang et al, 2013; Pereira et al, 2014; Pereira et al, 2015; Cui et al, 2017; Villagarcía et al, 2018). Moreover, Pereira et al (2014) have reported that hepatic fatty acid accumulation may activate PKCδ to increase NADPH oxidase-dependent oxidative stress, which further promotes the expression of IKK-β/JNK to impair hepatic insulin signaling pathway and finally cause hepatic insulin resistance.…”

Section: The Role Of Hepatic Free Fatty Acid Accumulation On Hepatic supporting

confidence: 85%

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns

Nie

Huang

et al. 2019

Front. Pharmacol.

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Metabolic syndrome, characterized by central obesity, hypertension, and hyperlipidemia, increases the morbidity and mortality of cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and other metabolic diseases. It is well known that insulin resistance, especially hepatic insulin resistance, is a risk factor for metabolic syndrome. Current research has shown that hepatic fatty acid accumulation can cause hepatic insulin resistance through increased gluconeogenesis, lipogenesis, chronic inflammation, oxidative stress and endoplasmic reticulum stress, and impaired insulin signal pathway. Mitochondria are the major sites of fatty acid β-oxidation, which is the major degradation mechanism of fatty acids. Mitochondrial dysfunction has been shown to be involved in the development of hepatic fatty acid–induced hepatic insulin resistance. Mitochondrial autophagy (mitophagy), a catabolic process, selectively degrades damaged mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial dynamics and function. Therefore, mitophagy can promote mitochondrial fatty acid oxidation to inhibit hepatic fatty acid accumulation and improve hepatic insulin resistance. Here, we review advances in our understanding of the relationship between mitophagy and hepatic insulin resistance. Additionally, we also highlight the potential value of mitophagy in the treatment of hepatic insulin resistance and metabolic syndrome.

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Section: The Role Of Hepatic Free Fatty Acid Accumulation On Hepatic supporting

confidence: 85%

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns

Nie

Huang

et al. 2019

Front. Pharmacol.

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“…Journal of Endocrinology (Villagarcía et al 2018). Those findings, together with results from our study, indicated that NAC could improve dyslipidemia in obese and estrogen-deprived conditions.…”

Section: :2supporting

confidence: 78%

N-acetylcysteine with low-dose estrogen reduces cardiac ischemia-reperfusion injury

Sivasinprasasn

Palee

Chattipakorn

et al. 2019

Journal of Endocrinology

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Myocardial damage and mitochondrial dysfunction caused by cardiac ischemia-reperfusion (I/R) injury are intensified by endogenous estrogen deprivation. Although N-acetylcysteine (NAC) exerted cardioprotective effects, its benefits when used in combination with hormone therapy are unknown. We tested the hypothesis that a combination of NAC with low-dose estrogen improves cardiometabolic function and protects cardiac mitochondria against I/R injury, to a similar extent to regular-dose estrogen treatment, in estrogen-deprived rats. Female Wistar rats had a bilateral ovariectomy (OVX) or sham operation. Twelve weeks after the operation, OVX rats were treated with regular-dose estrogen (E; 50 µg/kg/day), low-dose estrogen (e; 25 µg/kg/day), NAC (N; 100 mg/kg/day) or combined low-dose estradiol with NAC (eN) for 4 weeks (n = 6/group). Metabolic parameters, echocardiography, heart rate variability and then cardiac I/R protocol involving 30-min coronary artery ligation, followed by 120-min reperfusion, were performed. OVX rats had increased body weight, visceral fat, fasting plasma glucose, HOMA-IR index, triglycerides, cholesterol and LDL levels (P < 0.05 vs sham). Only OVX-E and OVX-eN had a similarly improved HOMA-IR index. LVEF was increased in all treatment groups, but HRV was restored only by OVX-E and OVX-eN. After I/R, myocardial infarct size was decreased in both OVX-E and OVX-eN groups. OVX-E and OVX-eN rats similarly had a reduced mitochondrial ROS level and increased mitochondrial membrane potential in the ischemic myocardium. In conclusion, combined NAC with low-dose estrogen and regular-dose estrogen therapy similarly improve cardiometabolic function, prevent cardiac mitochondrial dysfunction and reduces the infarct size in estrogen-deprived rats with cardiac I/R injury.

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“…Villagarcía et al [75] evaluated the effect of long-term N-Acetyl-L-Cysteine (NAC) in hypothalamic obese rats. The rats are characterized by prediabetes, dyslipidemia, obesity, increased inflammatory state, and liver dysmetabolism accompanied by increased oxidative stress.…”

Section: Possible Therapeutic Effects Of Antioxidants: From Bench mentioning

confidence: 99%

Associations of Oxidative Stress and Postoperative Outcome in Liver Surgery with an Outlook to Future Potential Therapeutic Options

Senoner

Schindler

Stättner

et al. 2019

Oxidative Medicine and Cellular Longevity

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Several types of surgical procedures have shown to elicit an inflammatory stress response, leading to substantial cytokine production and formation of oxygen-based or nitrogen-based free radicals. Chronic liver diseases including cancers are almost always characterized by increased oxidative stress, in which hepatic surgery is likely to potentiate at least in the short term and hereby furthermore impair the hepatic redox state. During liver resection, intermittent inflow occlusion is commonly applied to prevent excessive blood loss but resulting ischemia and reperfusion of the liver have been linked to increased oxidative stress, leading to impairment of cell functions and subsequent cell death. In the field of liver transplantation, ischemia/reperfusion injury has extensively been investigated in the last decades and has recently been in the scientific focus again due to increased use of marginal donor organs and new machine perfusion concepts. Therefore, given the intriguing role of oxidative stress in the pathogenesis of numerous diseases and in the perioperative setting, the interest for a therapeutic antioxidative agent has been present for several years. This review is aimed at giving an introduction to oxidative stress in surgical procedures in general and then examines the role of oxidative stress in liver surgery in particular, discussing both transplantation and resection. Results from studies in the animal and human settings are included. Finally, potential therapeutic agents that might be beneficial in reducing the burden of oxidative stress in hepatic diseases and during surgery are presented. While there is compelling evidence from animal models and a limited number of clinical studies showing that oxidative stress plays a major role in both liver resection and transplantation and several recent studies have suggested a potential for antioxidative treatment in chronic liver disease (e.g., steatosis), the search for effective antioxidants in the field of liver surgery is still ongoing.

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N-Acetyl-l-Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats

Cited by 14 publications

References 66 publications

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns

N-acetylcysteine with low-dose estrogen reduces cardiac ischemia-reperfusion injury

Associations of Oxidative Stress and Postoperative Outcome in Liver Surgery with an Outlook to Future Potential Therapeutic Options

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