Abstract

L-arginine (Arg) is a semiessential amino acid with several physiological functions. N-Carbamylglutamate (NCG) can promote the synthesis of endogenous Arg in mammals. However, the roles of Arg or NCG on hepatic inflammation and apoptosis in suckling lambs suffering from intrauterine growth restriction (IUGR) are still unclear. The current work is aimed at examining the effects of dietary Arg and NCG on inflammatory and hepatocyte apoptosis in IUGR suckling lambs. On day 7 after birth, 48 newborn Hu lambs were selected from a cohort of 432 twin lambs. Normal-birthweight and IUGR Hu lambs were allocated randomly (n = 12/group) to control (CON), IUGR, IUGR+1% Arg, or IUGR+0.1% NCG groups. Lambs were fed for 21 days from 7 to 28 days old. Compared with CON lambs, relative protein 53 (P53), apoptosis antigen 1 (Fas), Bcl-2-associated X protein (Bax), caspase-3, cytochrome C, tumor necrosis factor alpha (TNF-α), nuclear factor kappa-B (NF-κB) p65, and NF-κB pp65 protein levels were higher (P < 0.05) in liver from IUGR lambs, whereas those in liver from IUGR lambs under Arg or NCG treatment were lower than those in IUGR lambs. These findings indicated that supplementing Arg or NCG reduced the contents of proinflammatory cytokines at the same time when the apoptosis-related pathway was being suppressed, thus suppressing the IUGR-induced apoptosis of hepatic cells.

Highlights

  • Maternal undernutrition is associated with intrauterine growth retardation (IUGR) which is detrimental to survival, growth, and metabolism and the long-term performance of the offspring in various animals [1,2,3]

  • This study was conducted to address the changes in the growth, proinflammatory cytokines, hepatic inflammatory response, and apoptosis in IUGR suckling lambs supplemented with L-Arg or NCG

  • The findings of this study revealed a decrease in the final BW, liver weight, hepatic DNA concentration, protein-toDNA ratio, and proliferation index with a decrease in the hepatic apoptotic cell number in IUGR suckling lambs compared to the normal body weight (NBW) lambs and IUGR lambs supplemented with either L-Arg or NCG

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Summary

Introduction

Maternal undernutrition is associated with intrauterine growth retardation (IUGR) which is detrimental to survival, growth, and metabolism and the long-term performance of the offspring in various animals [1,2,3]. IUGR alters the development of fetal organs and tissues and may negatively affect their functions in adult life with a predisposition to developing metabolic disorders [4,5,6,7,8,9,10]. IUGR has been reported to reduce fetal liver growth and disrupt the metabolic, endocrine, and antioxidant defense functions of the liver in fetal, neonatal, postnatal, and adult life stages [11,12,13,14]. There is a potential to ameliorate the adverse effects of IUGR on postnatal health and performance through early life nutrition interventions with key functional nutrients [15,16,17]

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