N-Acetylcysteine protects against intrauterine growth retardation-induced intestinal injury via restoring redox status and mitochondrial function in neonatal piglets
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Intrauterine growth retardation (IUGR) is detrimental to the intestinal development of neonates, yet satisfactory treatment strategies remain limited. This study was, therefore, conducted using neonatal piglets as a model to investigate the potential of N-acetylcysteine (NAC) to alleviate intestinal damage caused by IUGR.
Seven normal birth weight (NBW) and fourteen IUGR neonatal male piglets were selected and then fed a basal milk diet (NBW-CON and IUGR-CON groups) or a basal milk diet supplemented with 1.2 g NAC per kg of diet (IUGR-NAC group) from 7 to 21 days of age (n = 7). Parameters associated with the severity of intestinal injury, villus morphology and ultrastructural structure, redox status, and mitochondrial function were analyzed.
Compared with the NBW-CON piglets, the IUGR-CON piglets exhibited decreased villus height and greater numbers of apoptotic cells in jejunum, along with the increases in malondialdehyde and protein carbonyl concentrations and a decreased adenosine triphosphate (ATP) content. Treatment with NAC significantly increased jejunal superoxide dismutase activity, reduced glutathione: oxidized glutathione ratio, and the mRNA abundance of nuclear respiratory factor 2, heme oxygenase 1, and superoxide dismutase 2 in the IUGR-NAC piglets compared with the IUGR-CON piglets. In addition, NAC improved the efficiency of mitochondrial oxidative metabolism and ATP generation, ameliorated mitochondrial swelling, and inhibited the overproduction of mitochondrial superoxide anion in the jejunal mucosa.
Dietary supplementation of NAC shows promise for attenuating the early intestinal injury of young piglets with IUGR, probably through its antioxidant action to restore redox status and mitochondrial function.
KeywordsIntrauterine growth retardation N-Acetylcysteine Intestinal damage Mitochondrial function Redox status Piglet
This research was funded by the National Natural Science Foundation of China (Grant numbers 31772634 and 31802094), the Natural Science Foundation of Jiangsu Province (Grant number BK20180531), the Postdoctoral Research Foundation of China (Grant number 2018M632320), the Open Project of Shanghai Key Laboratory of Veterinary Biotechnology (Grant number klab201710), and the Phase II Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. The authors would like to thank all co-workers for their help and cooperation in this trial.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
The use of animals for this research was approved by the Institutional Animal Care and Use Committee of Nanjing Agricultural University.
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