Hao Zhang;Yi Zheng;Xia Zha;Xiaoyun Liu;Yuxiang Ma;Juan J. Loor;Mabrouk Elsabagh;Mengzhi Wang;Hao Zhang;Honghua Jian

Department of Pediatrics, Northern Jiangsu People’s Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, Chin;Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China;Department of Animal Production and Technology, Faculty of Agricultural Sciences and Technologies, Niğde Ömer Halisdemir University, Nigde 51240, Turkey;Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL, 61801, USA; Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt

Colon;Endoplasmic reticulum stress;IUGR lambs;L-arginine;N-carbamylglutamate;Redox statu

Previous studies have revealed that dietary N-carbamylglutamate (NCG) or L-arginine (Arg) improves small intestinal integrity and immune function in suckling Hu lambs that have experienced intrauterine growth retardation (IUGR). Whether these nutrients alter redox status and apoptosis in the colon of IUGR lambs is still unknown. This study, therefore, aimed at investigating whether dietary supplementation of Arg or NCG alters colonic redox status, apoptosis and endoplasmic reticulum (ER) stress and the underlying mechanism of these alterations in IUGR suckling Hu lambs. Forty-eight 7-d old Hu lambs, including 12 with normal birth weight (4.25 ± 0.14 kg) and 36 with IUGR (3.01 ± 0.12 kg), were assigned to 4 treatment groups (n = 12 each; 6 males and 6 females) for 3 weeks. The treatment groups were control (CON), IUGR, IUGR + Arg and IUGR + NCG. Relative to IUGR lambs, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content, as well as proliferation index, were higher (P < 0.05) whereas reactive oxygen species (ROS), malondialdehyde (MDA) levels and apoptotic cell numbers were lower (P < 0.05) in colonic tissue for both IUGR + Arg and NCG lambs. Both mRNA and protein levels of C/EBP homologous protein 10 (CHOP10), B-cell lymphoma/leukaemia 2 (Bcl-2) -associated X protein (Bax), apoptosis antigen 1 (Fas), activating transcription factor 6 (ATF6), caspase 3, and glucose-regulated protein 78 (GRP78) were lower (P < 0.05) while glutathione peroxidase 1 (GPx1), Bcl-2 and catalase (CAT) levels were higher (P < 0.05) in colonic tissue for IUGR + Arg and IUGR + NCG lambs compared with IUGR lambs. Based on our results, dietary NCG or Arg supplementation can improve colonic redox status and suppress apoptosis via death receptor-dependent, mitochondrial and ER stress pathways in IUGR suckling lambs.