N-acetylcysteine attenuates intrauterine growth retardation-induced hepatic damage in suckling piglets by improving glutathione synthesis and cellular homeostasis.

Abstract

The objective of the present study was to test the hypothesis that N-acetylcysteine (NAC) may play beneficial roles against intrauterine growth retardation (IUGR)-induced hepatic damage in suckling piglets. Fourteen IUGR and seven normal birth weight (NBW) neonatal male piglets were selected. Piglets were weaned at 7days of postnatal age and fed the control formula milk (NBW-CON and IUGR-CON groups) or the control formula milk supplemented with 1.2g/kg NAC (IUGR-NAC group) for 14days (n=7). The plasma and liver samples were analyzed for the parameters related to hepatic damage, redox status, apoptosis, and autophagy. Compared with the NBW-CON group, IUGR-CON group exhibited increased activities of plasma aminotransferases, increased numbers of apoptotic hepatocytes, as well as higher concentrations of protein carbonyl, malondialdehyde (MDA), microtubule-associated protein 1 light chain 3 beta, and phospholipid-conjugated form (MAP1LC3B-II), along with a decrease in the content of reduced glutathione (GSH). NAC treatment increased GSH content and GSH-to-oxidized GSH ratio in the liver of IUGR-NAC group, most likely owing to the improved activities of γ-glutamine-cysteine ligase, γ-glutamine-cysteine synthetase, and glutathione reductase. The hepatic protein carbonyl and MDA contents were decreased in the IUGR-NAC group compared with the IUGR-CON group. In addition, NAC-treated piglets had an increased content of B cell lymphoma/leukemia 2 protein, whereas a decreased expression level of MAP1LC3B-II in the liver. NAC may have beneficial effects in improving GSH synthesis and cellular homeostasis in the liver of IUGR suckling piglets.