The nitric oxide synthase 2 pathway is targeted by both pro- and anti-inflammatory treatments in the immature human intestine

Nitric Oxide - Biology and Chemistry

Volumn 66, Issue , 2017, Pages 53-61

  Ferretti, Emanuela ^a   Tremblay, Eric ^b   Thibault, Marie Pier ^b   Grynspan, David ^a   Burghardt, Karolina M ^c   Bettolli, Marcos ^a   Babakissa, Corentin ^b   Levy, Emile ^d   Beaulieu, Jean François ^b  

^a UNIVERSITY OF OTTAWA   (Canada)

^b UNIVERSITY OF SHERBROOKE   (Canada)

^c HOSPITAL FOR SICK CHILDREN   (Canada)

^d UNIVERSITY OF MONTREAL   (Canada)

Author keywords

Anti oxidant; Epithelial barrier; Epithelial cells; Inflammation; Intestinal mucosa; NO synthase 2

Indexed keywords

ARGINASE 1; ARGINASE 2; ARGININE; CITRULLINE; CLAUDIN 1; CLAUDIN 2; CLAUDIN 7; DUAL OXIDASE 2; EPIDERMAL GROWTH FACTOR; GLUTAMINASE; GLUTATHIONE PEROXIDASE 2; INDOMETACIN; INDUCIBLE NITRIC OXIDE SYNTHASE; MANGANESE SUPEROXIDE DISMUTASE; OCCLUDIN; ORNITHINE CARBAMOYLTRANSFERASE; ORNITHINE OXOACID AMINOTRANSFERASE; OXIDOREDUCTASE; UNCLASSIFIED DRUG; ANTIINFLAMMATORY AGENT; GASTROINTESTINAL AGENT;

AMINO ACID METABOLISM; ARTICLE; BIOINFORMATICS; CELL JUNCTION; CONTROLLED STUDY; EPITHELIUM CELL; EXPLANT; GENE EXPRESSION PROFILING; HUMAN; HUMAN TISSUE; ILEUM; INFANT; INFLAMMATION; MICROARRAY ANALYSIS; NECROTIZING ENTEROCOLITIS; OXIDATIVE STRESS; POLYMERASE CHAIN REACTION; PREGNANCY; PREMATURITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; SMALL INTESTINE; DRUG EFFECTS; ENZYMOLOGY; FETAL RESEARCH; METABOLISM; ORGAN CULTURE TECHNIQUE; SIGNAL TRANSDUCTION;

ANTI-INFLAMMATORY AGENTS; ARGININE; CITRULLINE; EPIDERMAL GROWTH FACTOR; FETAL RESEARCH; GASTROINTESTINAL AGENTS; HUMANS; ILEUM; INDOMETHACIN; NITRIC OXIDE SYNTHASE TYPE II; ORGAN CULTURE TECHNIQUES; SIGNAL TRANSDUCTION;

EID: 85015417905     PISSN: 10898603     EISSN: 10898611     Source Type: Journal    
DOI: 10.1016/j.niox.2017.03.003     Document Type: Article

References (82)

1. [1] Henry, M.C., Moss, R.L., Necrotizing enterocolitis. Annu. Rev. Med. 60 (2009), 111–124.
2. [2] Neu, J., Walker, W.A., Necrotizing enterocolitis. N. Engl. J. Med. 364 (2011), 255–264.
3. [3] Yee, W.H., Soraisham, A.S., Shah, V.S., Aziz, K., Yoon, W., Lee, S.K., Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics 129 (2012), e298–304.
4. [4] Nanthakumar, N., Meng, D., Goldstein, A.M., Zhu, W., Lu, L., Uauy, R., Llanos, A., Claud, E.C., Walker, W.A., The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. PLoS One, 6, 2011, e17776.
5. [5] Neu, J., Chen, M., Beierle, E., Intestinal innate immunity: how does it relate to the pathogenesis of necrotizing enterocolitis. Semin. Pediatr. Surg. 14 (2005), 137–144.
6. [6] Berseth, C.L., Gut motility and the pathogenesis of necrotizing enterocolitis. Clin. Perinatol. 21 (1994), 263–270.
7. [7] Dicken, B.J., Sergi, C., Rescorla, F.J., Breckler, F., Sigalet, D., Medical management of motility disorders in patients with intestinal failure: a focus on necrotizing enterocolitis, gastroschisis, and intestinal atresia. J. Pediatr. Surg. 46 (2011), 1618–1630.
8. [8] Crissinger, K.D., Regulation of hemodynamics and oxygenation in developing intestine: insight into the pathogenesis of necrotizing enterocolitis. Acta Paediatr. Suppl. 396 (1994), 8–10.
9. [9] Young, C.M., Kingma, S.D., Neu, J., Ischemia-reperfusion and neonatal intestinal injury. J. Pediatr., 158, 2011, e25 8.
10. [10] Claud, E.C., Walker, W.A., Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. Faseb J. 15 (2001), 1398–1403.
11. [11] Claud, E.C., Walker, W.A., Bacterial colonization, probiotics, and necrotizing enterocolitis. J. Clin. Gastroenterol. 42:Suppl 2 (2008), S46–S52.
12. [12] Clark, J.A., Doelle, S.M., Halpern, M.D., Saunders, T.A., Holubec, H., Dvorak, K., Boitano, S.A., Dvorak, B., Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment. Am. J. Physiol. Gastrointest. Liver Physiol. 291 (2006), G938–G949.
13. [13] Tremblay, E., Thibault, M.P., Ferretti, E., Babakissa, C., Bertelle, V., Bettolli, M., Burghardt, K.M., Colombani, J.F., Grynspan, D., Levy, E., Lu, P., Mayer, S., Menard, D., Mouterde, O., Renes, I.B., Seidman, E.G., Beaulieu, J.F., Gene expression profiling in necrotizing enterocolitis reveals pathways common to those reported in Crohn's disease. BMC Med. Genomics, 9, 2016, 6.
14. [14] Cekmez, F., Purtuloglu, T., Aydemir, G., Aydinoz, S., Fidanci, K., Karaoglu, A., Babacan, O., Canpolat, F.E., Cetinkaya, M., Tunc, T., Suleymanoglu, S., Comparing beneficial effects of inhaled nitric oxide to L-arginine in necrotizing enterocolitis model in neonatal rats. Pediatr. Surg. Int. 28 (2012), 1219–1224.
15. [15] Chokshi, N.K., Guner, Y.S., Hunter, C.J., Upperman, J.S., Grishin, A., Ford, H.R., The role of nitric oxide in intestinal epithelial injury and restitution in neonatal necrotizing enterocolitis. Semin. Perinatol. 32 (2008), 92–99.
16. [16] Tripp, M.A., Tepperman, B.L., Effect of nitric oxide on integrity, blood flow and cyclic GMP levels in the rat gastric mucosa: modulation by sialoadenectomy. Br. J. Pharmacol. 115 (1995), 344–348.
17. [17] Corsetti, M., Vos, R., Gevers, A., Demedts, I., Janssens, J., Tack, J., Influence of nitric oxide synthase inhibition on the motility and sensitivity of distal colon in man. Neurogastroenterol. Motil., 25, 2013, e256 62.
18. [18] Groneberg, D., Konig, P., Koesling, D., Friebe, A., Nitric oxide-sensitive guanylyl cyclase is dispensable for nitrergic signaling and gut motility in mouse intestinal smooth muscle. Gastroenterology 140 (2011), 1608–1617.
19. [19] Katsube, T., Tsuji, H., Onoda, M., Nitric oxide attenuates hydrogen peroxide-induced barrier disruption and protein tyrosine phosphorylation in monolayers of intestinal epithelial cell. Biochim. Biophys. Acta 1773 (2007), 794–803.
20. [20] Oliveira-Lima, O.C., Bernardes, D., Xavier Pinto, M.C., Esteves Arantes, R.M., Carvalho-Tavares, J., Mice lacking inducible nitric oxide synthase develop exacerbated hepatic inflammatory responses induced by Plasmodium berghei NK65 infection. Microbes Infect. 15 (2013), 903–910.
21. [21] Mattila, J.T., Thomas, A.C., Nitric oxide synthase: non-canonical expression patterns. Front. Immunol., 5, 2014, 478.
22. [22] Alican, I., Kubes, P., A critical role for nitric oxide in intestinal barrier function and dysfunction. Am. J. Physiol. 270 (1996), G225–G237.
23. [23] Blikslager, A.T., Roberts, M.C., Nitric oxide and the intestinal epithelial barrier: does it protect or damage the gut?. J. Pediatr. Gastroenterol. Nutr. 25 (1997), 439–440.
24. [24] Everts, B., Stotzer, P., Olsson, M., Kilander, A., Pettersson, A., Increased luminal nitric oxide concentrations in the small intestine of patients with coeliac disease. Eur. J. Clin. Invest 29 (1999), 692–696.
25. [25] Katada, K., Bihari, A., Badhwar, A., Yoshida, N., Yoshikawa, T., Potter, R.F., Cepinskas, G., Hindlimb ischemia/reperfusion-induced remote injury to the small intestine: role of inducible nitric-oxide synthase-derived nitric oxide. J. Pharmacol. Exp. Ther. 329 (2009), 919–927.
26. [26] Morin, M.J., Unno, N., Hodin, R.A., Fink, M.P., Differential expression of inducible nitric oxide synthase messenger RNA along the longitudinal and crypt-villus axes of the intestine in endotoxemic rats. Crit. Care Med. 26 (1998), 1258–1264.
27. [27] Grishin, A., Bowling, J., Bell, B., Wang, J., Ford, H.R., Roles of nitric oxide and intestinal microbiota in the pathogenesis of necrotizing enterocolitis. J. Pediatr. Surg. 51 (2016), 13–17.
28. [28] Nair, R.R., Warner, B.B., Warner, B.W., Role of epidermal growth factor and other growth factors in the prevention of necrotizing enterocolitis. Semin. Perinatol. 32 (2008), 107–113.
29. [29] Sullivan, P.B., Lewindon, P.J., Cheng, C., Lenehan, P.F., Kuo, B.S., Haskins, J.R., Goodlad, R.A., Wright, N.A., de la Iglesia, F.A., Intestinal mucosa remodeling by recombinant human epidermal growth factor(1-48) in neonates with severe necrotizing enterocolitis. J. Pediatr. Surg. 42 (2007), 462–469.
30. [30] Halpern, M.D., Dominguez, J.A., Dvorakova, K., Holubec, H., Williams, C.S., Meza, Y.G., Ruth, M.C., Dvorak, B., Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced by epidermal growth factor. J. Pediatr. Gastroenterol. Nutr. 36 (2003), 126–133.
31. [31] Menard, D., Arsenault, P., Pothier, P., Biologic effects of epidermal growth factor in human fetal jejunum. Gastroenterology 94 (1988), 656–663.
32. [32] Menard, D., Corriveau, L., Arsenault, P., Differential effects of epidermal growth factor and hydrocortisone in human fetal colon. J. Pediatr. Gastroenterol. Nutr. 10 (1990), 13–20.
33. [33] Menard, D., Tremblay, E., Ferretti, E., Babakissa, C., Perron, N., Seidman, E.G., Levy, E., Beaulieu, J.F., Anti-inflammatory effects of epidermal growth factor on the immature human intestine. Physiol. Genomics 44 (2012), 268–280.
34. [34] Knight, D.B., The treatment of patent ductus arteriosus in preterm infants. A review and overview of randomized trials. Semin. Neonatol. 6 (2001), 63–73.
35. [35] Rajadurai, V.S., Yu, V.Y., Intravenous indomethacin therapy in preterm neonates with patent ductus arteriosus. J. Paediatr. Child. Health 27 (1991), 370–375.
36. [36] Dollberg, S., Lusky, A., Reichman, B., Patent ductus arteriosus, indomethacin and necrotizing enterocolitis in very low birth weight infants: a population-based study. J. Pediatr. Gastroenterol. Nutr. 40 (2005), 184–188.
37. [37] O'Donovan, D.J., Baetiong, A., Adams, K., Chen, A., Smith, E.O., Adams, J.M., Weisman, L.E., Necrotizing enterocolitis and gastrointestinal complications after indomethacin therapy and surgical ligation in premature infants with patent ductus arteriosus. J. Perinatol. 23 (2003), 286–290.
38. [38] Perron, N., Tremblay, E., Ferretti, E., Babakissa, C., Seidman, E.G., Levy, E., Ménard, D., Beaulieu, J.-F., Deleterious effects of indomethacin in the mid-gestation human intestine. Genomics 101 (2013), 171–177.
39. [39] Tremblay, E., Ferretti, E., Babakissa, C., Seidman, E.G., Levy, E., Menard, D., Beaulieu, J.F., Gene-expression profile analysis in the mid-gestation human intestine discloses greater functional immaturity of the colon as compared with the ileum. J. Pediatr. Gastroenterol. Nutr. 52 (2011), 670–678.
40. [40] Badurdeen, S., Mulongo, M., Berkley, J.A., Arginine depletion increases susceptibility to serious infections in preterm newborns. Pediatr. Res. 77 (2015), 290–297.
41. [41] Amin, H.J., Zamora, S.A., McMillan, D.D., Fick, G.H., Butzner, J.D., Parsons, H.G., Scott, R.B., Arginine supplementation prevents necrotizing enterocolitis in the premature infant. J. Pediatr. 140 (2002), 425–431.
42. [42] Di Lorenzo, M., Bass, J., Krantis, A., Use of L-arginine in the treatment of experimental necrotizing enterocolitis. J. Pediatr. Surg. 30 (1995), 240–241 235-40; discussion.
43. [43] Richir, M.C., Siroen, M.P., van Elburg, R.M., Fetter, W.P., Quik, F., Nijveldt, R.J., Heij, H.A., Smit, B.J., Teerlink, T., van Leeuwen, P.A., Low plasma concentrations of arginine and asymmetric dimethylarginine in premature infants with necrotizing enterocolitis. Br. J. Nutr. 97 (2007), 906–911.
44. [44] Ioannou, H.P., Diamanti, E., Piretzi, K., Drossou-Agakidou, V., Augoustides-Savvopoulou, P., Plasma citrulline levels in preterm neonates with necrotizing enterocolitis. Early Hum. Dev. 88 (2012), 563–566.
45. [45] Wu, G., Morris, S.M. Jr., Arginine metabolism: nitric oxide and beyond. Biochem J 336:Pt 1 (1998), 1–17.
46. [46] Ligthart-Melis, G.C., van de Poll, M.C., Boelens, P.G., Dejong, C.H., Deutz, N.E., van Leeuwen, P.A., Glutamine is an important precursor for de novo synthesis of arginine in humans. Am. J. Clin. Nutr. 87 (2008), 1282–1289.
47. [47] van de Poll, M.C., Siroen, M.P., van Leeuwen, P.A., Soeters, P.B., Melis, G.C., Boelens, P.G., Deutz, N.E., Dejong, C.H., Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism. Am. J. Clin. Nutr. 85 (2007), 167–172.
48. [48] Wu, G., Synthesis of citrulline and arginine from proline in enterocytes of postnatal pigs. Am. J. Physiol. 272 (1997), G1382–G1390.
49. [49] Wu, G., Knabe, D.A., Arginine synthesis in enterocytes of neonatal pigs. Am. J. Physiol. 269 (1995), R621–R629.
50. [50] Morris, S.M. Jr., Regulation of enzymes of the urea cycle and arginine metabolism. Annu. Rev. Nutr. 22 (2002), 87–105.
51. [51] Nussler, A.K., Billiar, T.R., Liu, Z.Z., Morris, S.M. Jr., Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine macrophage cell line. Implications for regulation of nitric oxide production. J. Biol. Chem. 269 (1994), 1257–1261.
52. [52] Tan, C., Mui, A., Dedhar, S., Integrin-linked kinase regulates inducible nitric oxide synthase and cyclooxygenase-2 expression in an NF-kappa B-dependent manner. J. Biol. Chem. 277 (2002), 3109–3116.
53. [53] Driver, G.A., Veale, R.B., Modulation of integrin-linked kinase (ILK) expression in human oesophageal squamous cell carcinoma cell lines by the EGF and TGFbeta1 growth factors. Cancer Cell Int., 6, 2006, 12.
54. [54] Gunzel, D., Yu, A.S., Claudins and the modulation of tight junction permeability. Physiol. Rev. 93 (2013), 525–569.
55. [55] Liu, X., Yang, G., Geng, X.R., Cao, Y., Li, N., Ma, L., Chen, S., Yang, P.C., Liu, Z., Microbial products induce claudin-2 to compromise gut epithelial barrier function. PLoS One, 8, 2013, e68547.
56. [56] Suzuki, T., Regulation of intestinal epithelial permeability by tight junctions. Cell Mol. Life Sci. 70 (2013), 631–659.
57. [57] Schoultz, I., McKay, C.M., Graepel, R., Phan, V.C., Wang, A., Soderholm, J., McKay, D.M., Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C. Am. J. Physiol. Gastrointest. Liver Physiol. 303 (2012), G536–G545.
58. [58] Somasundaram, S., Sigthorsson, G., Simpson, R.J., Watts, J., Jacob, M., Tavares, I.A., Rafi, S., Roseth, A., Foster, R., Price, A.B., Wrigglesworth, J.M., Bjarnason, I., Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat. Aliment. Pharmacol. Ther. 14 (2000), 639–650.
59. [59] Clark, J.A., Gan, H., Samocha, A.J., Fox, A.C., Buchman, T.G., Coopersmith, C.M., Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis. Am. J. Physiol. Gastrointest. Liver Physiol. 297 (2009), G471–G479.
60. [60] Quirino, I.E., Cardoso, V.N., Santos, R., Evangelista, W.P., Arantes, R.M., Fiuza, J.A., Gloria, M.B., Alvarez-Leite, J.I., Batista, M.A., Correia, M.I., The role of L-arginine and inducible nitric oxide synthase in intestinal permeability and bacterial translocation. JPEN J. Parenter. Enter. Nutr. 37 (2013), 392–400.
61. [61] Chapman, J.C., Liu, Y., Zhu, L., Rhoads, J.M., Arginine and citrulline protect intestinal cell monolayer tight junctions from hypoxia-induced injury in piglets. Pediatr. Res. 72 (2012), 576–582.
62. [62] Karp, S.M., Koch, T.R., Oxidative stress and antioxidants in inflammatory bowel disease. Dis. Mon. 52 (2006), 199–207.
63. [63] Pavlick, K.P., Laroux, F.S., Fuseler, J., Wolf, R.E., Gray, L., Hoffman, J., Grisham, M.B., Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. Free Radic. Biol. Med. 33 (2002), 311–322.
64. [64] El Hassani, R.A., Benfares, N., Caillou, B., Talbot, M., Sabourin, J.C., Belotte, V., Morand, S., Gnidehou, S., Agnandji, D., Ohayon, R., Kaniewski, J., Noel-Hudson, M.S., Bidart, J.M., Schlumberger, M., Virion, A., Dupuy, C., Dual oxidase2 is expressed all along the digestive tract. Am. J. Physiol. Gastrointest. Liver Physiol. 288 (2005), G933–G942.
65. [65] Bae, Y.S., Choi, M.K., Lee, W.J., Dual oxidase in mucosal immunity and host-microbe homeostasis. Trends Immunol. 31 (2010), 278–287.
66. [66] Esworthy, R.S., Aranda, R., Martin, M.G., Doroshow, J.H., Binder, S.W., Chu, F.F., Mice with combined disruption of Gpx1 and Gpx2 genes have colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 281 (2001), G848–G855.
67. [67] Fukai, T., Ushio-Fukai, M., Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid. Redox Signal 15 (2011), 1583–1606.
68. [68] Segui, J., Gironella, M., Sans, M., Granell, S., Gil, F., Gimeno, M., Coronel, P., Pique, J.M., Panes, J., Superoxide dismutase ameliorates TNBS-induced colitis by reducing oxidative stress, adhesion molecule expression, and leukocyte recruitment into the inflamed intestine. J. Leukoc. Biol. 76 (2004), 537–544.
69. [69] Omatsu, T., Naito, Y., Handa, O., Hayashi, N., Mizushima, K., Qin, Y., Hirata, I., Adachi, S., Okayama, T., Kishimoto, E., Takagi, T., Kokura, S., Ichikawa, H., Yoshikawa, T., Involvement of reactive oxygen species in indomethacin-induced apoptosis of small intestinal epithelial cells. J. Gastroenterol. 44:Suppl 19 (2009), 30–34.
70. [70] Ford, H., Watkins, S., Reblock, K., Rowe, M., The role of inflammatory cytokines and nitric oxide in the pathogenesis of necrotizing enterocolitis. J. Pediatr. Surg. 32 (1997), 275–282.
71. [71] Nadler, E.P., Dickinson, E., Knisely, A., Zhang, X.R., Boyle, P., Beer-Stolz, D., Watkins, S.C., Ford, H.R., Expression of inducible nitric oxide synthase and interleukin-12 in experimental necrotizing enterocolitis. J. Surg. Res. 92 (2000), 71–77.
72. [72] Cetin, S., Leaphart, C.L., Li, J., Ischenko, I., Hayman, M., Upperman, J., Zamora, R., Watkins, S., Ford, H.R., Wang, J., Hackam, D.J., Nitric oxide inhibits enterocyte migration through activation of RhoA-GTPase in a SHP-2-dependent manner. Am. J. Physiol. Gastrointest. Liver Physiol. 292 (2007), G1347–G1358.
73. [73] Schwentker, A., Billiar, T.R., Nitric oxide and wound repair. Surg. Clin. North Am. 83 (2003), 521–530.
74. [74] Thomas, D.D., Heinecke, J.L., Ridnour, L.A., Cheng, R.Y., Kesarwala, A.H., Switzer, C.H., McVicar, D.W., Roberts, D.D., Glynn, S., Fukuto, J.M., Wink, D.A., Miranda, K.M., Signaling and stress: the redox landscape in NOS2 biology. Free Radic. Biol. Med. 87 (2015), 204–225.
75. [75] Shin, C.E., Falcone, R.A. Jr., Stuart, L., Erwin, C.R., Warner, B.W., Diminished epidermal growth factor levels in infants with necrotizing enterocolitis. J. Pediatr. Surg. 35 (2000), 173–176 discussion 177.
76. [76] Warner, B.B., Ryan, A.L., Seeger, K., Leonard, A.C., Erwin, C.R., Warner, B.W., Ontogeny of salivary epidermal growth factor and necrotizing enterocolitis. J. Pediatr. 150 (2007), 358–363.
77. [77] Sullivan, P.B., Brueton, M.J., Tabara, Z.B., Goodlad, R.A., Lee, C.Y., Wright, N.A., Epidermal growth factor in necrotising enteritis. Lancet 338 (1991), 53–54.
78. [78] Fiorucci, S., Santucci, L., Gresele, P., Faccino, R.M., Del Soldato, P., Morelli, A., Gastrointestinal safety of NO-aspirin (NCX-4016) in healthy human volunteers: a proof of concept endoscopic study. Gastroenterology 124 (2003), 600–607.
79. [79] Carlstrom, M., Persson, A.E., Larsson, E., Hezel, M., Scheffer, P.G., Teerlink, T., Weitzberg, E., Lundberg, J.O., Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension. Cardiovasc Res. 89 (2011), 574–585.
80. [80] Bjorne, H.H., Petersson, J., Phillipson, M., Weitzberg, E., Holm, L., Lundberg, J.O., Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. J. Clin. Invest 113 (2004), 106–114.
81. [81] Zwolinska-Wcislo, M., Brzozowski, T., Ptak-Belowska, A., Targosz, A., Urbanczyk, K., Kwiecien, S., Sliwowski, Z., Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis. World J. Gastroenterol. 17 (2011), 4076–4089.
82. [82] Wu, G., Jaeger, L.A., Bazer, F.W., Rhoads, J.M., Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications. J. Nutr. Biochem. 15 (2004), 442–451.