The prophylactic effect of L-Arginine in an experimental model of acute ischemic colitis. A histopathological and biochemical (malondialdehyde levels) evaluation (original) (raw)
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Protective Effects of L-Arginine on Rat Terminal Ileum Subjected to Ischemia/Reperfusion
Journal of Pediatric Gastroenterology and Nutrition, 2008
Objectives: Studies have shown that nitric oxide (NO) may play a major role in sustaining mucosal integrity; however, NO has been also implicated in the pathogenesis of ischemia/ reperfusion (I/R)-related tissue injury. We investigated the effects of L-arginine and N G-nitro L-arginine methyl ester (L-NAME) on the acetylcholine-induced contractile response of ileum and the levels of malondialdehyde (MDA) and reduced glutathione (GSH). Histopathological changes were also evaluated in ileal preparations. Materials and Methods: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (3 hours). Four groups were designed: shamoperated control; I/R; I/R and L-arginine pretreatment; and I/ R and L-NAME pretreatment. After reperfusion, ileum specimens were collected to determine the parameters mentioned above. Results: Following reperfusion, a significant decrease in acetylcholine-induced contractile response, an increase in lipid peroxidation, a decrease in GSH content, and mucosal damage of the ileal preparations were observed. We showed that decreased contractility, increased lipid peroxidation, and reduced GSH content have been reversed by L-arginine but not by L-NAME. Mucosal injury was significantly lowered in the L-arginine group. Conclusions: Treatment with L-arginine exerted a protective effect in intestinal I/R injury, which was mediated in part by regulating MDA and GSH levels, consequently ameliorating impaired contractile response and mucosal injury. JPGN 46:29-35, 2008.
Transplantation Proceedings, 2008
Objective. Usualy an experimental necrotizing enterocolitis experimental model, we Investigated nitric oxide levels in intestinal tissues of newborn mice with or without L-arginine therapy during sessions of ischemia and reoxygenation. Methods. Twenty-six newborn mice from the Wistar EPM-1 lineage, weighing from 4.5 to 6.2 g, were randomly assigned to three groups: G-I/R, hypoxia and reoxygenation; G-Arg, L-arginine treatment I/R; and G-CTL, controls. G-I/R and G-Arg mice underwent twice a day during their first 3 days of life exposure to gas chambers with 100% CO 2 for 5 minutes at 22°C before reoxygenation with 100% O 2 for another 5 minutes. After 12 hours, all animals were sedated, laparotomized, and had samples of ileum and colon taken and-either formalin fixed histopathologic examations or frozen to Ϫ80°C for estimation of tissue nitric oxide levels. Intestinal injuries were classified according to the criteria of Chiu et al. Results. The G-I/R and G-Arg groups showed injuries characteristic of necrotizing enterocolitis (NEC) with an improved structural preservation rate in G-Arg. The concentration of nitric oxide in the Ileum was much higher with G-Arg (16.5 Ϯ 4.9; P ϭ 0.0019) G-I/R (7.3 Ϯ 2.0). This effect was not observed in the colon: G-I/R ϭ 10.7 Ϯ 4.6 versus G-Arg ϭ 15.5 Ϯ 8.7 (P ϭ .2480). Conclusion. Supply of L-arginine increased tissue levels of nitricoxide and reduced morphologic intestinal injury among mice undergoing I/R.
Study of L-arginine in intestinal lesions caused by ischemia-reperfusion in rats
Transplant Proc, 2012
To examine whether treatment with L-arginine (ARG), a substrate of nitric oxide biosynthesis, attenuated intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rats with ARG (100 mg/kg intravenously) or saline solution (SS) before 60 minutes of I produced by occlusion of the superior mesenteric artery and/or during 120 minutes of R. After I or I/R, we isolated 2-cm jejunal segments for mounting in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl with the use of a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Jejunal contractions were similar in the sham and IϩARG, but reduced in IϩSS, I/RϩSS, and I/RϩARG groups. Jejunal enteric nerves were damaged in IϩSS, IRϩSS, and IRϩARG, but not in the IϩARG group, suggesting that ARG attenuate intestinal dysfunctions due to I but not to R.
Oral arginine improves intestinal recovery following ischemia-reperfusion injury in rat
Pediatric Surgery International, 2005
Arginine and nitric oxide are critical to the normal physiology of the gastrointestinal tract and maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluate the effects of oral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis following intestinal ischemia–reperfusion (IR) in the rat. Male Sprague–Dawley rats were divided into three experimental groups: sham rats underwent laparotomy and superior mesenteric artery mobilization, IR rats underwent superior mesenteric artery occlusion for 30 min following by 24 h of reperfusion, and IR-ARG rats were treated with enteral arginine given in drinking water (2%) 48 h before and following IR. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. A nonparametric Kruskal–Wallis ANOVA test was used for statistical analysis with p
Long-Term Enteral Arginine Supplementation in Rats with Intestinal Ischemia and Reperfusion
Journal of Surgical Research, 2012
Background. The effects of short-term enteral arginine supplementation on intestinal ischemiareperfusion (IR) injury have been widely studied, especially the ischemic preconditioning supplementation. The aim of this study was to investigate the effects of long-term intra-duodenal supplementation of arginine on intestinal morphology, arginine-associated amino acid metabolism, and inflammatory responses in rats with intestinal IR. Materials and Methods. Male Wistar rats with or without three hours of ileal ischemia underwent duodenal cannulation for continuous infusion of formula with 2% arginine or commercial protein powder for 7 d. The serological examinations, plasma amino acid and cytokine profiles, and intestinal morphology were assessed. Results. Intestinal IR injury had significant impacts on the decreases in circulating red blood cells, hemoglobin, ileum mass, and villus height and crypt depth of the distal jejunum. In addition, arginine supplementation decreased serum cholesterol and increased plasma arginine concentrations. In rats with intestinal IR injury, arginine supplementation significantly decreased serum nitric oxide, plasma citrulline and ornithine, and the mucosal protein content of the ileum. Conclusions. These results suggest that long-term intra-duodenal arginine administration may not have observable benefits on intestinal morphology or inflammatory response in rats with intestinal ischemia and reperfusion injury. Therefore, the necessity of long-term arginine supplementation for patients with intestinal ischemia and reperfusion injury remains questionable and requires further investigation.
Effect of L-arginine on the course of experimental colitis
Clinical Nutrition, 2001
L-Arg is the substrate for nitric oxide, and also for L-ornithine which, in turn, is the precursor for the synthesis of collagen and polyamines. By these di¡erent metabolic pathways, L-Arg is involved in the mechanisms of in£ammation, tissue repair and ¢brosis. Thus, the aim of this study was to assess the e¡ect of both di¡erent amounts of L-Arg supplementation and L-Arg-free diets upon colonic in£ammatory damage and ¢brosis in experimental colitis. Methods: Sprague^Dawley rats with trinitrobenzene sulphonic acid (TNBS)-induced colitis received increasing doses of L-Arg (30, 100, 500 mg/day), or D-Arg (500 mg/day). In a second experiment, two L-Arg-free diets (one supplemented with L-Gly) were compared to a L-Arg diet. Nitrite/nitrate release in the lumen of the colon and colonic damage were evaluated. In the ¢rst experiment, tissue collagen levels and colonic mucosal proliferation were also assessed. Results: In the acute phase of colitis, intracolonic nitrite/nitrate levels were signi¢cantly higher in the 100 and 500 mg supplemented L-Arg groups than in D-Arg group. However, only rats treated with 500 mg of L-Arg showed moderately higher in£ammatory and ¢brosis colonic scores than the D-Arg treated rats.There was no signi¢cant in£uence of L-Argfree diets on the course ofTNBS-induced colitis. However, L-Arg diet accelerated weight gain both pre-and post-TNBS. Conclusions:These results suggest that normal amounts of L-Arg in the diet are not harmful, whereas both absence of L-Arg or supplementation with high doses of this amino acid may be deleterious. In the former this might be due to a decrease of nitrogen retention in injured rats, whereas in the latter it may result from both nitric oxide-mediated tissue damage and collagen deposition.
l-Arginine Supplementation Protects Against Hepatic Ischemia–Reperfusion Lesions in Rabbits
Transplantation Proceedings, 2009
We evaluated the effects of a substrate in the biosynthesis of nitric oxide (NO)-L-arginine (LARG)-on hepatic lesions caused by ischemia/reperfusion (I/R) injury in rabbit livers. Rabbits were pretreated with LARG (150 mg/kg IV) or saline solution 0.9% (SS) before the hepatic I/R procedure. The effects of LARG on hepatic injury were evaluated before and after I/R. The warm hepatic I/R procedure produced profound acute liver injury, as indicated by elevated values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH), as well as a high apoptotic cell count. All changes were attenuated by treatment with LARG before the hepatic I/R procedure. These results suggested that LARG produced protective effects on hepatic I/R lesions. This protective effect of LARG was probably associated with blocking generation of superoxide anions during the hepatic I/R procedure.
International Journal of Medicine and Medical Research, 2014
Background. Hepatic ischemia-reperfusion (I/R) injury occurs upon restoration of hepatic blood flow after a period of ischemia. Objective. The study establishes that stimulation or blockade of nitric oxide synthesis has a protective effect during ischemia-reperfusion. Methods. Male albino rats which were divided into four equal groups: sham-operated control, ischemia and reperfusion group (0.9 % saline i.p.) for 3 days, group pre-treated with L-arginine (25 mg/kg i.p.), group pre-treated with L-NAME (10 mg/kg i.p.) for 3 days before ischemia-reperfusion maneuver. Complete ischemia of the median and left hepatic lobes was induced by clamping the left branches of the portal vein and the hepatic artery for 45 min. Rats were sacrificed after 3-h reperfusion. Nitric oxide synthase 3 (endothelial) and nitric oxide synthase 2 (inducible) expression, nitric oxide stabile metabolites (NO 2 , NO 3) content, AST and ALT activities were determined. Histological examination of liver tissue was performed. Conclusions. Relative NO deficiency, due to eNOS inhibition, is central in the pathogenesis of hepatic ischemia reperfusion injury. Replacing NO content with either precursors or via donor drugs represents novel methods in ameliorating ischemia-reperfusion injury.
L-arginine in the ischemic phase protects against liver ischemia-reperfusion injury
Acta Cirurgica Brasileira, 2012
PURPOSE: To investigate the effects of intravenous L-arginine (LG) infusion on liver morphology, function and proinflammatory response of cytokines during the early phase of ischemia-reperfusion injury (IRI). METHODS: Thirty rabbits were subjected to 60 minutes of hepatic ischemia and 120 minutes of reperfusion. An intravenous injection of saline or L-arginine was administered five minutes before the ischemia and five minutes before initiating the reperfusion and at the 55 th and 115 th minutes after the ischemia. Samples were collected for histological analysis of the liver and measurements of the serum AST, ALT and LDH and the cytokines IL-6 and TNF-alpha. RESULTS: It was observed a significant reduction of sinusoidal congestion, cytoplasmic vacuolization, infiltration of polymorphonuclear leukocyte, nuclear pyknosis, necrosis and steatosis in liver tissue, as well as AST, ALT and LDH after injection of LG in the ischemia (p <0.001). Lower levels of IL-6 and TNF-alpha were associated with LG infusion during ischemia. Higher levels these proteins were observed in animals receiving LG during reperfusion. CONCLUSION: L-arginine protects the liver against ischemia/reperfusion injury, mainly when is administered during the ischemic phase.