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Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide

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Abstract

The neonatal small intestine is susceptible to damage by endotoxin, but effective methods for prevention and treatment are lacking. N-acetylcysteine (NAC) is a widely used precursor of l-cysteine for animal cells and plays an important role in protecting cells against oxidative stress. This study was conducted with the lipopolysaccharide (LPS)-challenged piglet model to determine the effects of NAC on intestinal function. Eighteen piglets were randomly allocated into control, LPS and LPS + NAC groups. The control and LPS groups were fed a corn- and soybean meal-based diet, and the LPS + NAC group was fed the basal diet +500 mg/kg NAC. On days 10, 13 and 20 of the trial, the LPS and LPS + NAC groups received intraperitoneal administration of LPS (100 μg/kg BW), whereas the control piglets received saline. On day 20 of the trial, d-xylose (0.1 g/kg BW) was orally administrated to all piglets 2 h after LPS or saline injection, and blood samples were collected 1 h thereafter. One hour blood xylose test was used to measure intestinal absorption capacity and mucosal integrity, and diamine oxidase (DAO) was used as a marker of intestinal injury. On day 21 of the trial, pigs were killed to obtain the intestinal mucosa. Compared to the control, LPS challenge reduced (P < 0.05) the concentrations of d-xylose (a marker of intestinal absorption) in plasma, activities of DAO in the jejunal mucosa, the ratio of villus height to crypt depth in the jejunal mucosa, RNA/DNA and protein/DNA in the jejunal and ileal mucosae, while increasing (P < 0.05) DAO activity in plasma and caspase-3 expression in the intestinal mucosa. The adverse effects of LPS were partially ameliorated (P < 0.05) by NAC supplementation. Moreover, NAC prevented the LPS-induced decrease in claudin-1 and occludin expression in the jejunal and ileal mucosae. Collectively, these results indicate that dietary NAC supplementation alleviates the mucosal damage and improves the absorptive function of the small intestine in LPS-challenged piglets.

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Abbreviations

BSA:

Bovine serum albumin

BW:

Body weight

DAO:

Diamine oxidase

HSP 70:

Heat shock protein 70

LPS:

Lipopolysaccharide

NAC:

N-acetylcysteine

PBS:

Phosphate-buffered saline

SD:

Standard deviation of the mean

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Acknowledgments

This research was jointly supported by the 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) 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).

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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, Wuhan, 430023, China

    Yongqing Hou, Lei Wang, Wei Zhang, Zhenguo Yang, Binying Ding, Huiling Zhu, Yulan Liu & Yinsheng Qiu

  2. Research Center for Healthy Breeding of Livestock and Poultry, Hunan Engineering and Research Center of Animal and Poultry Science and Key Laboratory for Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Hunan, 410125, China

    Yulong Yin

  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. Wei Zhang
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  4. Zhenguo Yang
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Correspondence to Yongqing Hou or Guoyao Wu.

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Hou, Y., Wang, L., Zhang, W. et al. Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids 43, 1233–1242 (2012). https://doi.org/10.1007/s00726-011-1191-9

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