Nitric Oxide Interferes With Hypoxia Signaling During Colonic Inflammation

Caria, Cíntia Rabelo e Paiva; Moscato, Camila Henrique; Tomé, Renata Bortolin Guerra; Pedrazzoli, José; Ribeiro, Marcelo Lima; Gambero, Alessandra

doi:10.1590/s0004-28032014000400007

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…The latter is related to pro-inflammatory cytokines such as tumor necrosis factor α [TNF α], interleukin 1 (IL-1), and interferon γ (IFN-γ), so its overexpression must be regulated [94]. Increased NO synthesis by iNOS is a process that occurs during intestinal inflammation [95], which occurred in the experimental animals due to the presence of DSS.…”

Section: Discussionmentioning

confidence: 99%

Modification of In Vitro and In Vivo Antioxidant Activity by Consumption of Cooked Chickpea in a Colon Cancer Model

et al. 2020

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Chickpea has been classified as a nutraceutical food due to its phytochemical compounds, showing antioxidant, anti-inflammatory, and anticancer activity. To investigate this, we evaluated the effect of cooking on the nutritional and non-nutritional composition and the in vitro and in vivo antioxidant activity of chickpea seed. The latter was determined by the variation in the concentration of nitric oxide (NO), oxidized carbonyl groups (CO), malondialdehyde (MDA), and the expression of 4-hydroxy-2-nonenal (4-HNE) in the colon of male BALB/c mice fed with a standard diet with 10 and 20% cooked chickpea (CC). We induced colon cancer in mice by administering azoxymethane/dextran sulfate sodium (AOM/DSS); for the evaluation, these were sacrificed 1, 7, and 14 weeks after the induction. Results show that cooking does not significantly modify (p < 0.05) nutritional compounds; however, it decreases the concentration of non-nutritional ones and, consequently, in vitro antioxidant activity. The in vivo evaluation showed that animals administered with AOM/DSS presented higher concentrations of NO, CO, MDA, and 4-HNE than those in animals without AOM/DSS administration. However, in the three evaluated times, these markers were significantly reduced (p < 0.05) with CC consumption. The best effect on the oxidation markers was with the 20% CC diet, demonstrating the antioxidant potential of CC.

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Section: Discussionmentioning

confidence: 99%

Modification of In Vitro and In Vivo Antioxidant Activity by Consumption of Cooked Chickpea in a Colon Cancer Model

et al. 2020

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“…Positive areas in five randomly selected microscopic fields (x40 magnification) per section were measured using analysis software (BZ-X analyzer, Keyence, Osaka, Japan). For pimonidazole staining, Hypoxyprobe Omni kit (Abcam) was used according to the manufacturer's protocol (21). Positive areas in five randomly selected microscopic fields (magnification, x40) per section were measured using analysis software (BZ-X analyzer; Keyence) and the mean percentage of positive area was calculated.…”

Section: Histological Examinations (Mice)mentioning

confidence: 99%

Microcirculatory disturbance in acute liver injury

et al. 2021

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Microcirculatory disturbance is thought to be involved in the pathogenesis of acute liver injury (ALI). The current study examined the pathophysiologic role of hepatic microcirculatory disturbance in patients with ALI and in mouse models of ALI. Using serum aminotransferase (ALT)/lactate dehydrogenase (LDH) ratio as a hypoxic marker, 279 patients with ALI were classified into the low ALT/LDH ratio (ALT/LDH ≤1.5) and high ALT/LDH ratio group (ALT/LDH >1.5). In the low ALT/LDH ratio group, serum ALT, LDH, fibrinogen degradation products and prothrombin time-international normalized ratio were increased relative to the high ALT/LDH ratio group. Histologically, hepatic expression of tissue factor (TF) and hypoxia-related proteins was enhanced in the low ALT/LDH ratio group, and this was accompanied by sinusoidal fibrin deposition. Sinusoidal hypercoagulation and intrahepatic hypoxia was also analyzed in two different mouse models of ALI; Concanavalin A (ConA) mice and Galactosamine/tumor necrosis factor (TNF)-α (G/T) mice. Serum ALT/LDH ratio in ConA mice was significantly lower compared with G/T mice. Pimonidazole staining revealed the upregulation of hypoxia-related proteins in ConA mice. Recombinant human soluble thrombomodulin improved liver damage in ConA mice in association with reduced sinusoidal hypercoagulation and intrahepatic hypoxia. The present study provides evidence that serum ALT/LDH ratio aids in the identification of patients with ALI and intrahepatic hypoxia as a result of microcirculatory disturbance. The results facilitate the improved understanding of the pathogenesis of ALI, thereby offering a novel therapeutic strategy against ALI, which arises from sinusoidal hypercoagulation.

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“…Administration of a nitric oxide synthase inhibitor lowers oxidative injury, 29 and the effect is relevant to the interference of HIF-1α–mediated hypoxia signaling. 30 Paradoxically, NO can also enhance the expression of peroxisome proliferator-activated receptor γ, which, in turn, alleviates the inflammatory response and oxidative stress. 31 Thus, the effector function of NO in IBD is more complex than previously thought.…”

Section: Methodsmentioning

confidence: 99%

Arginine metabolism regulates the pathogenesis of inflammatory bowel disease

Guo

Zhou

et al. 2022

Nutrition Reviews

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The pathogenesis of inflammatory bowel disease (IBD) is related to genetic susceptibility, enteric dysbiosis, and uncontrolled, chronic inflammatory responses that lead to colonic tissue damage and impaired intestinal absorption. As a consequence, patients with IBD are prone to nutrition deficits after each episode of disease resurgence. Nutritional supplementation, especially for protein components, is often implemented during the remission phase of IBD. Notably, ingested nutrients could affect the progression of IBD and the prognostic outcome of patients; therefore, they should be cautiously evaluated prior to being used for IBD intervention. Arginine (Arg) is a semi-essential amino acid required for protein synthesis and intimately associated with gut pathophysiology. To help optimize arginine-based nutritional intervention strategies, the present work summarizes that during the process of IBD, patients manifest colonic Arg deficiency and the turbulence of Arg metabolic pathways. The roles of Arg–nitric oxide (catalyzed by inducible nitric oxide synthase) and Arg–urea (catalyzed by arginases) pathways in IBD are debatable; the Arg–polyamine and Arg–creatine pathways are mainly protective. Overall, supplementation with Arg is a promising therapeutic strategy for IBD; however, the dosage of Arg may need to be carefully tailored for different individuals at different disease stages. Additionally, the combination of Arg supplementation with inhibitors of Arg metabolic pathways as well as other treatment options is worthy of further exploration.

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Nitric Oxide Interferes With Hypoxia Signaling During Colonic Inflammation

Cited by 4 publications

References 25 publications

Modification of In Vitro and In Vivo Antioxidant Activity by Consumption of Cooked Chickpea in a Colon Cancer Model

Modification of In Vitro and In Vivo Antioxidant Activity by Consumption of Cooked Chickpea in a Colon Cancer Model

Microcirculatory disturbance in acute liver injury

Arginine metabolism regulates the pathogenesis of inflammatory bowel disease

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