N-Acetyl-L-cysteine Protects the Enterocyte against Oxidative Damage by Modulation of Mitochondrial Function

Xiao, Hao; Wu, Miaomiao; Shao, Fangyuan; Guan, Guijian; Huang, Bo; Tan, Bie; Yin, Yulong

doi:10.1155/2016/8364279

Cited by 31 publications

(20 citation statements)

References 42 publications

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“…Contrary to the result of LPS challenge, NAC had no effect on intestinal function including cytokine expression, intestinal barrier function, and intestinal wound healing in NAC treatment without LPS challenge in IPEC-J2 cells. In agreement with the present study, it has been reported that only cell proliferation, mitochondrial respiration, lactate dehydrogenase concentration, and apoptosis were not affected by NAC in small intestinal epithelial cells 34 . The function of NAC might be inadequate, but it can be effective in special condition such as inflammation.…”

Section: Discussionsupporting

confidence: 94%

N-acetylcysteine modulates lipopolysaccharide-induced intestinal dysfunction

Lee

Kang²

2019

Sci Rep

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The gastrointestinal epithelium functions in nutrient absorption and pathogens barrier and its dysfunction directly affects livestock performance. N-Acetylcysteine (NAC) improves mucosal function, but its effects on intestinal functions at the molecular level remain unclear. Here, we performed gene expression profiling of the pig small intestine after dietary NAC treatment under LPS challenge and investigated the effects of NAC on intestinal epithelial cells in vitro. Dietary NAC supplementation under LPS challenge altered the small intestine expression of 959 genes related to immune response, inflammatory response, oxidation-reduction process, cytokine-cytokine receptor interaction, and the cytokine-mediated signalling, Toll-like receptor signalling pathway, Jak-STAT signalling pathway, and TNF signalling pathway. We then analysed the expression patterns of the top 10 altered genes, and found that NAC markedly stimulated HMGCS3 and LDHC expression in IPEC-J2 cells. In vitro, NAC pre-treatment significantly reduced TNF-α and NF-κB, TNF-α, IFN-γ, and IL-6 expression in LPS-induced IPEC-J2 cells. NAC treatment also significantly reduced oxidative stress in LPS-induced IPEC-J2 cells and alleviated intestinal barrier function and wound healing. Thus, NAC as a feed additive can enhance livestock intestinal health by modulating intestinal inflammation, permeability, and wound healing under LPS-induced dysfunction, improving our molecular understanding of the effects of NAC on the intestine.

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Section: Discussionsupporting

confidence: 94%

N-acetylcysteine modulates lipopolysaccharide-induced intestinal dysfunction

Lee

Kang²

2019

Sci Rep

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“…Previous work has also shown that NAC has beneficial effects on mitochondrial function through increased synthesis of pyruvate dehydrogenase, a key enzyme for mitochondrial energy metabolism, in the mouse liver in vivo (Zwingmann & Bilodeau, ) and elevated rates of mitochondrial respiration in porcine intestinal epithelial cells in vitro (Xiao et al . ). In this study, we demonstrate that acute treatment with NAC effectively increased the litter size and viable fetal number in DHT+insulin‐treated pregnant rats, thus supporting its therapeutic potential for reducing ROS‐mediated fetal loss under PCOS conditions.…”

Section: Discussionmentioning

confidence: 97%

Hyperandrogenism and insulin resistance‐induced fetal loss: evidence for placental mitochondrial abnormalities and elevated reactive oxygen species production in pregnant rats that mimic the clinical features of polycystic ovary syndrome

Zhang

Zhao

et al. 2019

The Journal of Physiology

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Key pointsr Women with polycystic ovary syndrome (PCOS) commonly suffer from miscarriage, but the underlying mechanisms remain unknown.r Herein, pregnant rats chronically treated with 5α-dihydrotestosterone (DHT) and insulin exhibited hyperandrogenism and insulin resistance, as well as increased fetal loss, and these features are strikingly similar to those observed in pregnant PCOS patients.r Fetal loss in our DHT+insulin-treated pregnant rats was associated with mitochondrial dysfunction, disturbed superoxide dismutase 1 and Keap1/Nrf2 antioxidant responses, over-production of reactive oxygen species (ROS) and impaired formation of the placenta.r Chronic treatment of pregnant rats with DHT or insulin alone indicated that DHT triggered many of the molecular pathways leading to placental abnormalities and fetal loss, whereas insulin often exerted distinct effects on placental gene expression compared to co-treatment with DHT and insulin.r Treatment of DHT+insulin-treated pregnant rats with the antioxidant N-acetylcysteine improved fetal survival but was deleterious in normal pregnant rats.r Our results provide insight into the fetal loss associated with hyperandrogenism and insulin resistance in women and suggest that physiological levels of ROS are required for normal placental formation and fetal survival during pregnancy.Yuehui Zhang is a professor and chief physician in the . She carried out postdoctoral research training in reproductive endocrinology at the University of Gothenburg, Sweden and obstetrics and gynaecology at the University of Pennsylvania, USA. Her research aims are to uncover the cellular and molecular mechanisms in aetiologies of polycystic ovary syndrome (PCOS) and other gynaecological diseases, as well as to develop an effective treatment for PCOS patients.Abstract Women with polycystic ovary syndrome (PCOS) commonly suffer from miscarriage, but the underlying mechanism of PCOS-induced fetal loss during pregnancy remains obscure and specific therapies are lacking. We used pregnant rats treated with 5α-dihydrotestosterone (DHT) and insulin to investigate the impact of hyperandrogenism and insulin resistance on fetal survival and to determine the molecular link between PCOS conditions and placental dysfunction during pregnancy. Our study shows that pregnant rats chronically treated with a combination of DHT and insulin exhibited endocrine aberrations such as hyperandrogenism and insulin resistance that are strikingly similar to those in pregnant PCOS patients. Of pathophysiological significance, DHT+insulin-treated pregnant rats had greater fetal loss and subsequently decreased litter sizes compared to normal pregnant rats. This negative effect was accompanied by impaired trophoblast differentiation, increased glycogen accumulation, and decreased angiogenesis in the placenta. Mechanistically, we report that over-production of reactive oxygen species (ROS) in the placenta, mitochondrial dysfunction, and disturbed superoxide dismutase 1 (SOD1) and Keap1/Nrf2 antioxidant responses constitute im...

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“…Although it is beyond the scope of functional amino acids, several indispensable amino acids, such as tryptophan and sulfur amino acids, have also attracted large attention recently (108–110). A growing evidence has revealed that supplementation of these amino acids beyond the current NRC requirement brought positive effects on intestinal health of weaned pigs by regulating host physiology, metabolism, oxidative status, and immunity (108–110). The modification of gut microbiota and their metabolites by these amino acids was also highly correlated to the enhanced gut barrier functions of weaned pigs (109).…”

Section: Nutritional Intervention On Intestinal Development and Healtmentioning

confidence: 99%

Nutritional Intervention for the Intestinal Development and Health of Weaned Pigs

et al. 2019

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Weaning imposes simultaneous stress, resulting in reduced feed intake, and growth rate, and increased morbidity and mortality of weaned pigs. Weaning impairs the intestinal integrity, disturbs digestive and absorptive capacity, and increases the intestinal oxidative stress, and susceptibility of diseases in piglets. The improvement of intestinal development and health is critically important for enhancing nutrient digestibility capacity and disease resistance of weaned pigs, therefore, increasing their survival rate at this most vulnerable stage, and overall productive performance during later stages. A healthy gut may include but not limited several important features: a healthy proliferation of intestinal epithelial cells, an integrated gut barrier function, a preferable or balanced gut microbiota, and a well-developed intestinal mucosa immunity. Burgeoning evidence suggested nutritional intervention are one of promising measures to enhance intestinal health of weaned pigs, although the exact protective mechanisms may vary and are still not completely understood. Previous research indicated that functional amino acids, such as arginine, cysteine, glutamine, or glutamate, may enhance intestinal mucosa immunity (i.e., increased sIgA secretion), reduce oxidative damage, stimulate proliferation of enterocytes, and enhance gut barrier function (i.e., enhanced expression of tight junction protein) of weaned pigs. A number of feed additives are marketed to assist in boosting intestinal immunity and regulating gut microbiota, therefore, reducing the negative impacts of weaning, and other environmental challenges on piglets. The promising results have been demonstrated in antimicrobial peptides, clays, direct-fed microbials, micro-minerals, milk components, oligosaccharides, organic acids, phytochemicals, and many other feed additives. This review summarizes our current understanding of nutritional intervention on intestinal health and development of weaned pigs and the importance of mechanistic studies focusing on this research area.

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N-Acetyl-L-cysteine Protects the Enterocyte against Oxidative Damage by Modulation of Mitochondrial Function

Cited by 31 publications

References 42 publications

N-acetylcysteine modulates lipopolysaccharide-induced intestinal dysfunction

N-acetylcysteine modulates lipopolysaccharide-induced intestinal dysfunction

Hyperandrogenism and insulin resistance‐induced fetal loss: evidence for placental mitochondrial abnormalities and elevated reactive oxygen species production in pregnant rats that mimic the clinical features of polycystic ovary syndrome

Nutritional Intervention for the Intestinal Development and Health of Weaned Pigs

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