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.
- 6.Burton GJ, Yung HW, Cindrova-Davies T et al (2009) Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia. Placenta 30:43–48. https://doi.org/10.1016/j.placenta.2008.11.003 CrossRefPubMedCentralGoogle Scholar
- 15.Perrone S, Tataranno ML, Negro S et al (2012) May oxidative stress biomarkers in cord blood predict the occurrence of necrotizing enterocolitis in preterm infants? J Matern Fetal Neonatal Med 25 Suppl 1:128–131. https://doi.org/10.3109/14767058.2012.663197
- 18.Friel JK, Friesen RW, Harding SV et al (2004) Evidence of oxidative stress in full-term healthy infants. Pediatr Res 56:878–882. https://doi.org/10.1203/01.PDR.0000146032.98120.43 CrossRefPubMedGoogle Scholar
- 24.Amrouche-Mekkioui I, Djerdjouri B (2012) N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice. Eur J Pharmacol 691:209–217. https://doi.org/10.1016/j.ejphar.2012.06.014 CrossRefPubMedGoogle Scholar
- 36.Ong MM, Wang AS, Leow KY et al (2006) Nimesulide-induced hepatic mitochondrial injury in heterozygous Sod2(+/-) mice. Free Radic Biol Med 40:420–429. https://doi.org/10.1016/j.freeradbiomed.2005.08.038 CrossRefPubMedGoogle Scholar
- 48.Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 48:749–762. https://doi.org/10.1016/j.freeradbiomed.2009.12.022 CrossRefPubMedPubMedCentralGoogle Scholar
- 56.Stepkowski TM, Kruszewski MK (2011) Molecular cross-talk between the NRF2/KEAP1 signaling pathway, autophagy, and apoptosis. Free Radic Biol Med 50:1186–1195. https://doi.org/10.1016/j.freeradbiomed.2011.01.033 CrossRefPubMedGoogle Scholar
- 64.Xiao H, Wu M, Shao F et al (2016) N-acetyl-l-cysteine protects the enterocyte against oxidative damage by modulation of mitochondrial function. Mediators Inflamm 2016:8364279. https://doi.org/10.1155/2016/8364279