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    Dietary Supplementation of L-Arginine and N-Carbamylglutamate Attenuated the Hepatic Inflammatory Response and Apoptosis in Suckling Lambs with Intrauterine Growth Retardation
    (Hindawi Ltd, 2020) Zhang, Hao; Fan, Yaotian; Elsabagh, Mabrouk; Guo, Shuang; Wang, Mengzhi; Jiang, Honghua
    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-alpha), nuclear factor kappa-B (NF-kappa B) p65, and NF-kappa B 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.
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    L-Arginine Inhibits Apoptosis of Ovine Intestinal Epithelial Cells through the L-Arginine-Nitric Oxide Pathway
    (Oxford Univ Press, 2020) Zhang, Hao; Zhao, Fangfang; Peng, Along; Guo, Shuang; Wang, Mengzhi; Elsabagh, Mabrouk; Loor, Juan J.
    Background: In nonruminants, many of the biological roles of L-arginine (Arg) at the intestinal level are mediated through the Arg-nitric oxide (Arg-NO) pathway. Whether the Arg-NO pathway is involved in controlling the immune response and viability in ovine intestinal epithelial cells (IOECs) is unclear. Objectives: The current study aimed to examine the role of the Arg-NO pathway in apoptosis, antioxidant capacity, and mitochondrial function of IOECs. Methods: The IOECs were incubated in Arg-free DMEM supplemented with 150 mu M Arg (CON) or 300 mu M Arg (ARG) alone or with 350 mu M Nw-nitro-L-arginine methyl ester hydrochloride (L-NAME) (CON + NAME, ARG + NAME) for 24 h. The reactive oxygen species (ROS) concentration, antioxidant capacity, and cell apoptotic percentage were determined. Results: Arg supplementation decreased (P < 0.05) the ROS concentration (38.9% and 22.7%) and apoptotic cell percentage (57.2% and 54.8%) relative to the CON and CON + NAME groups, respectively. Relative to the CON and ARG treatments, the L-NAME administration decreased (P < 0.05) the mRNA abundance of superoxide dismutase 2 (32% and 21.3%, respectively) and epithelial NO synthase (36% and 29.1%, respectively). Arg supplementation decreased (P < 0.05) the protein abundance of apoptosis antigen 1 (FAS) (52.0% and 43.9%) but increased (P < 0.05) those of nuclear respiratory factor 1 (31.3% and 22.9%) and inducible NO synthase (35.2% and 41.8%) relative to the CON and CON + NAME groups, respectively. Conclusions: The inhibition of apoptosis in IOECs due to the increased supply of Arg is associated with the mitochondria- and FAS-dependent pathways through the activity of the Arg-NO pathway. The findings help elucidate the role of the Arg-NO pathway in IOEC growth and apoptosis.