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N-acetylcysteine reduces inflammation in the small intestine by regulating redox, EGF and TLR4 signaling

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Abstract

This study determined whether N-acetylcysteine (NAC) could affect intestinal redox status, proinflammatory cytokines, epidermal growth factor (EGF), EGF receptor (EGFR), Toll-like receptor-4 (TLR4), and aquaporin-8 in a lipopolysaccharide (LPS)-challenged piglet model. Eighteen piglets (35-day-old) were randomly allocated into one of the three treatments (control, LPS and NAC). The control and LPS groups were fed a basal diet, and the NAC group received the basal diet +500 mg/kg NAC. On days 10, 13, and 20 of the trial, the LPS- and NAC-treated piglets received intraperitoneal administration of LPS (100 μg/kg BW), whereas the control group received the same volume of saline. On days 10 and 20, venous blood samples were obtained at 3 h post LPS or saline injection. On day 21 of the trial, piglets were killed to obtain the intestinal mucosa for analysis. Compared with the control group, LPS challenge reduced (P < 0.05) the activities of superoxide dismutase, catalase, and glutathione peroxidase in jejunal mucosae, while increasing (P < 0.05) the concentrations of malondialdehyde, H2O2, O2 ·− and the ratio of oxidized to reduced glutathione in jejunal mucosae, and concentrations of TNF-α, cortisol, interleukin-6, and prostaglandin E2 in both plasma and intestinal mucosae. These adverse effects of LPS were attenuated (P < 0.05) by NAC supplementation. Moreover, NAC prevented LPS-induced increases in abundances of intestinal HSP70 and NF-κB p65 proteins and TLR4 mRNA. NAC supplementation enhanced plasma EGF concentration and intestinal EGFR mRNA levels. Collectively, these results indicate that dietary NAC supplementation alleviates LPS-induced intestinal inflammation via regulating redox, EGF, and TLR4 signaling.

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Abbreviations

AQP:

Aquaporin

EGF:

Epidermal growth factor

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

HSP70:

Heat shock protein 70

LPS:

Lipopolysaccharide

NF-κB:

Nuclear factor κB

RT-PCR:

Real-time polymerase-chain reaction

TLR4:

Toll-like receptor 4

TNF-α:

Tumor necrosis factor-alpha

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Acknowledgments

This research was jointly supported by National Natural Science Foundation of China (Grant No. 30871801), National Natural Science Foundation of China (No. 30972213), Wuhan Disciplines Leaders Project (Grant No. 200951830554), the Program for Innovative Research Groups of Hubei Provincial Natural Science Foundation (Grant No. 2007ABC009), the Thousand-People Talent program at China Agricultural University, Chinese Universities Scientific Fund (2012RC024), and National Research Initiative Competitive Grants from the Animal Growth and Nutrient Utilization Program (2008-35206-18764) of the USDA National Institute of Food and Agriculture, and Texas AgriLife Research (H-82000).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023, Wuhan, China

    Yongqing Hou, Lei Wang, Dan Yi, Binying Ding, Zhenguo Yang, Jiao Li, Xing Chen & Yinsheng Qiu

  2. State Key Laboratory of Animal Nutrition, China Agricultural University, 100193, Beijing, China

    Guoyao Wu

  3. Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA

    Guoyao Wu

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  1. Yongqing Hou
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  2. Lei Wang
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  3. Dan Yi
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  4. Binying Ding
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  5. Zhenguo Yang
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  6. Jiao Li
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  7. Xing Chen
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  8. Yinsheng Qiu
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  9. Guoyao Wu
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Correspondence to Yongqing Hou or Guoyao Wu.

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Hou, Y., Wang, L., Yi, D. et al. N-acetylcysteine reduces inflammation in the small intestine by regulating redox, EGF and TLR4 signaling. Amino Acids 45, 513–522 (2013). https://doi.org/10.1007/s00726-012-1295-x

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  • DOI: https://doi.org/10.1007/s00726-012-1295-x

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