N-Acetylcysteine protects against intrauterine growth retardation-induced intestinal injury via restoring redox status and mitochondrial function in neonatal piglets.

Abstract

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 1.2g NAC per kg of diet (IUGR-NAC group) from 7 to 21days 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.