Effect of L-arginine on the course of experimental colitis (original) (raw)
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Experimental and Toxicologic Pathology, 2003
Inflammatory bowel disease (IBD) has been associated with an increased generation of nitric oxide (NO). Different authors have shown that NO in IBD can be either harmful or protective. The aim of this study was to investigate the efficiency of intrarectal (IR) and intraperitoneal (IP) application of N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor, in experimental acute colitis in the rats. Acute colitis was induced in rats by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol. Twenty-eight rats were divided into four groups. L-NAME (50 mg/kg/day) was administered IP (Group 1) and IR (Group 2) for 7 days following the day when colitis was induced. Group 3 rats were not given any treatment after induction of colitis. Control group rats were given saline solution IR instead of TNBS. The presence of hyperemia, inflammation and ulcer was evaluated to score of macroscopic morphologic damage. The severity of colitis was assessed by microscopic criteria including ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal atrophy, edema, inflammatory cell infiltration, and vascular dilatation. Rectal tissue myeloperoxidase (MPO) activity and serum-rectal tissue nitrite levels were measured. Serum and rectal tissue nitrite levels increased in Group 3 rats. Both IP and IR L-NAME treatment significantly reduced serum and rectal tissue nitrite levels, but no effect on MPO activity and histologic damage score was observed. Under the present conditions we concluded IR and IP L-NAME treatment, applied at the dosage of 50 mg/kg/day, does not have any protective effect on the colonic injury.
Annals of Gastroenterology
The aminoacid L-Arginine being the sole donor of nitric oxide synthesis in cases of intestinal ischemia, seems to play a protective role during experimental acute colon ischemia and reperfusion. We studied the effect of pretreatment with the aminoacid L-arginine in 144 Wistar rats who were subjected to experimental acute ischemic colitis (A.I.C.) and reperfusion of varying time periods (30, 60, 90 minutes). L-arginine was studied in comparison with Molcydomine and Caseine, two substances used for intestinal protection. Serum malondialdehyde (MDA) levels, a reliable marker which indicate the degree of tissue damage after ischemia-reperfusion, were lower in the L-arginine group, while the same group presented the lower level of histopathological damages. We conclude that pretreatment with L-arginine in rats subjected to A.I.C. attenuates the histopathophysiological damages.
Journal of Functional Foods, 2019
This study evaluated the mechanisms action of arginine in experimental model of ulcerative colitis. C57BL/6 mice were randomized into 4 groups: Control group (C): standard diet; Colitis group (Col): standard diet and DSS solution; Pretreated group (PT): diet supplementation with arginine before and during colitis induction; Treated group (T): diet supplementation with arginine during colitis induction. Colitis was induced by administration of 1.5% DSS for 5 days. Parameters such as intestinal permeability (IP), bacterial translocation (BT), histological and morphometric analysis, cytokines, immunoglobulin A, inflammatory infiltrate, oxidative stress, tight junction, iNOS 1 were performed. The Col group showed increased IP, BT, oxidative stress and inflammatory infiltrate in the colon. Arginine decreased IP, BT, oxidative stress and inflammatory infiltrate in the colon. Only, the group T reduced iNOS, cytokine IL-17, 2 and increased collagen area and cytokine TGF-β. 3 These results suggest that arginine can constitute in potential therapy for colitis. Jaggi, 2014). Though the etiology of IBD is not fully understood, several factors, including failure of intestinal barrier function, immunologic abnormalities, loss of tolerance to commensal bacteria, increase in inflammatory mediators and oxidative stress, are involved to the pathogenesis of IBD (Goyal, Rana, Ahlawat, Bijjem, & Kumar, 2014; Liu et al., 2017). An important adjuvant treatment is supplementation with amino acids, such as arginine, glutamine, glycine and proline, which have been reported in the literature as beneficial effects of this
Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity
Gut, 1995
Enhanced nitric oxide (NO) generation by stimulated NO synthase (NOS) activity may, through its oxidative metabolism contribute to tissue injury in experimental colitis. In this study the possible amelioration of experimental colitis by NG-nitro-Larginine methyl ester (L-NAME), an inhibitor of NOS activity, was evaluated. Colitis was induced in rats by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB) dissolved in 0.25 ml 50%/o ethanol or by flushing the colon of capsaicin pretreated rats with 2 ml of 50/0 acetic acid. In several experiments, L-NAME 0-1 mg/ml was added to the drinking water at the time of colitis induction with TNB or seven days before acetic acid treatment. Rats were killed at various time intervals after induction of colitis. A 10 cm distal colonic segment was isolated, weighed, lesion area measured, and explants organ cultured for 24 hours for determination of NO generation by the Greiss reaction. The rest of the mucosa was scraped for determination of myeloperoxidase and NOS activities and leukotriene generation. In TNB treated rats mean arterial pressure was also determined up to 72 hours after damage induction, with or without cotreatment with nitroprusside. L-NAME significantly decreased the extent of tissue injury in TNB treated rats. Seven days after TNB treatment lesion area was reduced by 55°/0, colonic weight by 37%, and myeloperoxidase and NOS activity by 590/o and 42%, respectively. Acetic acid induced colitis in capsaicin pretreated rats was also significantly decreased by L-NAME. Twenty four hours after acetic acid treatment lesion area was reduced by 61%/ colonic weight by 21%, and NOS activity by 39%. Mean (SEM) arterial blood pressure in TNB+L-NAME treated rats was 37.6 (8.1) mm Hg higher than in TNB treated rats, an effect that was only partially abolished by nitroprusside. These results show that inhibition of NO synthesis by an L-arginine analogue significantly ameliorates the extent of tissue injury in two models of experimental colitis, an effect that is not due only to its vasoconstrictor properties. Modulation of NO generation may be a novel therapeutic approach in inflammatory bowel disease. (Gut 1995; 37: 247-255)
PloS one, 2012
Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis (UC), results in substantial morbidity and is difficult to treat. New strategies for adjunct therapies are needed. One candidate is the semi-essential amino acid, L-arginine (L-Arg), a complementary medicine purported to be an enhancer of immunity and vitality in the lay media. Using dextran sulfate sodium (DSS) as a murine colonic injury and repair model with similarities to human UC, we assessed the effect of L-Arg, as DSS induced increases in colonic expression of the y(+) cationic amino acid transporter 2 (CAT2) and L-Arg uptake. L-Arg supplementation improved the clinical parameters of survival, body weight loss, and colon weight, and reduced colonic permeability and the number of myeloperoxidase-positive neutrophils in DSS colitis. Luminex-based multi-analyte profiling demonstrated that there was a marked reduction in proinflammatory cytokine and chemokine expression with L-Arg treatmen...
Nutrition Research, 2018
Heat stress (HS) induced by exposure to high ambient temperatures or prolonged excessive physical activities is known to primarily induce deleterious effects on the intestinal integrity by disrupting junctional complexes. Considering the association of L-arginine (L-Arg) with the improvement of gut function, the hypothesis of this study was to assess whether L-Arg supplementation can prevent the intestinal barrier disruption under HS conditions and to understand whether the L-Arg-induced effects are associated with maintaining nitric oxide (NO) as the major product of L-Arg metabolism. For this study, human colorectal adenocarcinoma (Caco-2) cells grown on Transwell inserts were pretreated with different L-Arg concentrations (0.4, 1, and 4 mmol/L), and after exposure to HS, markers of intestinal barrier integrity, stress-related markers, and NO levels were determined. L-Arg deprivation markedly increased the mRNA expression of heat shock protein 70 and heme-oxygenase-1 under HS conditions. The HS-induced drop in transepithelial electrical resistance values and increase in Lucifer Yellow permeability could be prevented by 4 mmol/L L-Arg supplementation. In turn, L-Arg mitigated the downregulation and delocalization of adherens junction protein E-cadherin in HS-exposed cells. NO and inducible NO synthase levels were significantly decreased in HS-exposed cells, whereas pretreatment with 4 mmol/L L-Arg prevented this decrease. Inhibition of inducible NO synthase by the NO synthase inhibitor L-NG-nitroarginine methyl ester abrogated the effect of L-Arg on preserving intestinal integrity under HS conditions as measured by transepithelial electrical resistance, Lucifer Yellow flux, and E-cadherin expression. In summary, L-Arg supplementation protects the intestinal epithelial integrity, at least partly, by maintaining NO synthesis under HS conditions.
Journal of neurogastroenterology and motility, 2018
The aim of present study is to estimate the effects of L. (MO) on visceral hypersensitivity (VH), defecation pattern and biochemical factors in 2 experimental models of irritable bowel syndrome (IBS) and the possible role of nitric oxide. Two individual models of IBS were induced in male Wistar-albino rats. In the acetic acid model, the animals were exposed to rectal distension and abdominal withdrawal reflex, and the defecation patterns were determined. In the restraint stress model, the colons of rats were removed and the levels of TNF-α, myeloperoxidase, lipid peroxidation, and antioxidant powers were determined. Rats had been treated with MO, L-NG-nitroarginine methyl ester (L-NAME), aminoguanidine (AG), MO + AG, or MO + L-NAME in the mentioned experimental models. Hypersensitive response to rectal distension and more stool defecation in control rats have been observed in comparison to shams. MO-300 significantly reduced VH and defecation frequency in comparison to controls. VH ...
L-arginine as a novel target for clinical intervention in inflammatory bowel disease
Exploration of Immunology, 2021
Arginase-1 (Arg1) and the inducible nitric oxide synthase 2 (NOS2) compete for the common substrate L-arginine, semi-essential amino acid, and central intestinal metabolite. Both enzymes exhibit various, sometimes opposing effects on immune responses, tissue regeneration, or microbial growth and replication. In sub-mucosal tissues of patients suffering from inflammatory bowel disease (IBD), similar as in experimental colitis, the expression and activity of both enzymes, Arg1 and NOS2 are more prominent than in respective controls. Accordingly, the metabolism of L-arginine is altered in IBD patients. Thus, L-arginine represents a promising medical target for clinical intervention in these devastating diseases. Previous studies primarily focused on the host side of L-arginine metabolism. Initial reports using Arg1 inhibitors generated conflicting results in murine colitis models. Subsequently, only the generation of conditional Arg1 knockout mice allowed reliable functional analyses o...
Role ofl-arginine, a substrate for nitric oxide-synthase, in gastroprotection and ulcer healing
Journal of Gastroenterology, 1997
Nitric oxide (NO) synthesized from L-arginine interacts with prostaglandins (PG) and sensory neuropeptides in the regulation of mucosal integrity, but the role of L-arginine, a substrate for NO-synthase, in gastroprotection and healing of chronic gastric ulcers has been little studied. In this study we compared the effects of intragastric (i.g.) and systemic (i.v.) administration of L-arginine or D-arginine on gastric secretion and acute gastric lesions provoked in rats by i.g. application of 100% ethanol, acidified aspirin (ASA), or the exposure to 3.5 h of water immersion and restraint stress (WRS). In addition, the effects of L-arginine on ulcer healing and the formation of new vessels (angiogenesis) were determined, using monoclonal antibody (MAb E-9). L-arginine (10-200mg/kg i.g.) failed to significantly affect gastric secretion but dose-dependently reduced the gastric lesions induced by 100% ethanol, ASA, and WRS, the doses inhibiting 50% of these lesions being 65, 94, and 72mg/kg, respectively. This protection was accompanied by a significant rise in the gastric blood flow (GBF), whereas L-arginine given i.v. failed to affect the ethanol-lesions and the GBF. D-arginine or the NOrelated amino acids-L-glutamine, L-citrulline, or Lornithine-failed to significantly influence these lesions. Suppression of the generation of mucosal PG by indomethacin or capsaicin-denervation attenuated the protection and hyperemia induced by L-arginine. The inhibition of constitutive NO synthase by L-NNA had no significant effect on the protection afforded by Larginine, but reduced the gastric hyperemia accompanying this protection. L-arginine (150mg/kg per day, i.g.