Nitric oxide in liver injury

Clemens, Mark G.

doi:10.1002/hep.510300148

Cited by 179 publications

(140 citation statements)

References 81 publications

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“…17 However, an endothelial dysfunction associated with decreased production of NO in the intrahepatic microcirculation has been extensively documented in the cirrhotic liver, 18,19 and these defects could directly contribute to the increased intrahepatic resistance typical of portal hypertension. 20 These observations provide per se a sound rationale for the use of nitrovasodilators in the treatment of portal hypertension.…”

Section: E Xperimental and Clinical Studies Have Indicated Thatmentioning

confidence: 95%

Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells

Failli¹,

et al. 2000

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Background & Aims:Nitrovasodilators have been proposed for the treatment of portal hypertension alone or in combination with ␤-blockers. In addition to their vasodilatory properties, nitric oxide (NO) donors may exert direct antifibrogenic properties. We evaluated the effect of nitroglycerin (NTG) and S-nitroso-N-acetyl penicillamine (SNAP) on the mitogenic and chemotactic properties of platelet-derived growth factor (PDGF)-BB and the modulation of the relative intracellular signaling pathways in fully activated human hepatic stellate cells (HSCs), a cell type that plays an active role in liver fibrogenesis and portal hypertension. Methods & Results: Both NTG and SNAP induced a dosedependent decrease in PDGF-induced DNA synthesis and cell migration, which was associated with a decrease in PDGF-induced intracellular Ca 2؉ increase and extracellular signal-regulated kinase (ERK) activity. These effects were not related to activation of the classic soluble guanylate cyclase (sGC)/guanosine 3 ,5 -cyclic monophosphate pathway; accordingly, Western blot analysis of HSC lysates revealed the absence of the ␣ 1 ␤ 1 ubiquitous subunits of sGC, whereas they were detectable in quiescent HSCs, freshly isolated from normal human liver. Conversely, both NTG and SNAP induced a more than 10 -20-fold increase in prostaglandin E 2 in cell supernatants within 1 minute, associated with an increase in intracellular adenosine 3 ,5 -cyclic monophosphate levels. Accordingly, the inhibitory effects of NO donors on PDGF action and signaling were eliminated after preincubation with ibuprofen. Conclusions: These results suggest that NO donors may exert a direct antifibrogenic action by inhibiting proliferation, motility, and contractility of HSCs in addition to a reduction of fibrillar extracellular matrix accumulation.

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Section: E Xperimental and Clinical Studies Have Indicated Thatmentioning

confidence: 95%

Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells

Failli¹,

et al. 2000

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“…This allows NO to (i) effectively scavenge intracellular superoxide anion, (ii) prevent platelet aggregation, and (iii) minimize adhesive interactions between neutrophils and the endothelial cell surface, increasing microvascular permeability [38].…”

Section: Imbalance Between No and Superoxide Anion Production By The mentioning

confidence: 99%

“…Thus, under these conditions many, if not all, of NO beneficial physiological actions are lost [38,[41][42][43][44][45][46].…”

Section: Imbalance Between No and Superoxide Anion Production By The mentioning

confidence: 99%

“…On the other hand, NO, especially that derived from endothelial nitric oxide synthase (eNOS) in sinusoidal endothelial cells, is able to counter the vasoconstriction effects of stellate cell activation, thus limiting perfusion deficits [37,38]. However, in the early stages of reperfusion, the increased concentration of ET reported in both plasma and liver parenchyma, as well as the low concentration of NO, most probably due to the low intracellular levels of NADPH and oxygen after the ischemic period [20], contribute both with a decrease in liver blood flow [39,40].…”

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confidence: 99%

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Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning

Cutrn

Perrelli

Cavalieri

et al. 2002

Free Radical Biology and Medicine

150

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Abstract-Hepatic ischemia/reperfusion injury has immediate and deleterious effects on the outcome of patients after liver surgery. The precise mechanisms leading to the damage have not been completely elucidated. However, there is substantial evidence that the generation of oxygen free radicals and disturbances of the hepatic microcirculation are involved in this clinical syndrome. Microcirculatory dysfunction of the liver seems to be mediated by sinusoidal endothelial cell damage and by the imbalance of vasoconstrictor and vasodilator molecules, such as endothelin (ET), reactive oxygen species (ROS), and nitric oxide (NO). This may lead to no-reflow phenomenon with release of proinflammatory cytokines, sinusoidal plugging of neutrophils, oxidative stress, and as an ultimate consequence, hypoxic cell injury and parenchymal failure. An inducible potent endogenous mechanism against ischemia/reperfusion injury has been termed ischemic preconditioning. It has been suggested that preconditioning could inhibit the effects of different mediators involved in the microcirculatory dysfunction, including endothelin, tumor necrosis factor-␣, and oxygen free radicals. In this review, we address the mechanisms of liver microcirculatory dysfunction and how ischemic preconditioning could help to provide new surgical and/or pharmacological strategies to protect the liver against reperfusion damage.

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“…Along with regulatory functions of NO, cytotoxic activity is detected, it can destroy DNA molecule, participate in the development of accelerated cell apoptosis and necrosis and permeation of cell membranes (Aguiar, Masse and Glibbs, (2005);Habib and Abi, 2011). NO molecule is synthesized in response to physiological need for NOsynthase enzyme from its metabolic precursor amino acids L-arginine, (Hirst and Robson, 2011).Currently, NO is considered as a signal molecule of the digestive system, since it stimulates relaxation of the smooth muscles of the esophagus, ventricle, small and large bowels, gall bladder, sphincter of ampulla of the pancreaticobiliary channel (Oddi) (Glemens, 1999;Leung Tung-Ming, Tipoe, Liong et al, 2010). Under physiological conditions, the endogenous NO -one of the mediators of exocrine pancreas secretion and mucin-producing cells of the gastric mucosa and bowels, stability, nonspecific and specific mucosal protection from the action of internal and external corrosive environmental factors (Abdullaev, Kleyner and Ruzibakiev, 1985;Pshennikova, 2011).The literature provides information on the status of NOS in the mucosa of the ventricle and bowels, its role in the pathogenesis of chronic hepatitis B, which determines the importance of the problem and the need for further research.…”

mentioning

confidence: 99%

State of Gastric Mucosa and Small Intestine Nitro-Ergic System During Chronic Heliotrine-Induced Hepatitis

Кульманова¹,

Сабирова²

2015

Adv. Sci.

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Abstract. In chronic heliotrine-induced hepatitis (CHH), in the tissues of the mucous membrane of the ventricle and bowels an endothelial dysfunction, characterized by a decreased level of NO is formed. In CHH, eNOS activity decreases due to the action of endotoxins on the gastric mucosa tissue and bowels entering to the central bloodstream from the liver. At the same time, they initiate iNOS and formation of ОNO 2 -that leads to inhibition of eNOS. It appears as potentiating effect of endotoxins' action produced in the liver in CHH in response to the inhibition of mucous membrane of the ventricle and bowels eNOS activity, initiation of iNOS, ОNO 2 -formation -an important cytotoxic / cytostatic compound, enhancing the proliferative and apoptotic processes, as a result, a high level of degradation and desquamation of the intestinal epithelium of the mucous membrane of the ventricle and bowels. Studied indicators of nitro-ergic system in the mucosa of the ventricle and bowels at CHH change in one direction. Keywords: chronic hepatitis, the system of nitric oxide, mucous membrane, ventricle, bowels.The Republic of Uzbekistan is in Central Asia wherein chronic viral hepatitis is widespread (Abdurakhmanov, 2010;Alimova and Nigmatov, 2003;Kosagovskaya and Volchkova, 2013).Improving in their diagnosis and treatment is connected with the knowledge of cellular and molecular mechanisms of inflammation in the liver, which reveal the essence of the pathological process (Ivashkin, 1998;Mayer, 2004;Sherlok and Duli, 1999).In the pathogenesis of hepatitis, particular importance falls on the abnormality of tissue homeostasis mucous membrane (MM) of the gastrointestinal tract, which is an important factor in favor congestion and venous stasis. All these suppose the involvement of the pathogenesis of destabilization of cellular and intracellular membranes in the mucosa of the gastrointestinal tract in patients with chronic hepatitis abnormalities of the endothelial function. An important regulator of the latter is nitric oxide (NO). Along with regulatory functions of NO, cytotoxic activity is detected, it can destroy DNA molecule, participate in the development of accelerated cell apoptosis and necrosis and permeation of cell membranes (Aguiar, Masse and Glibbs, (2005);Habib and Abi, 2011). NO molecule is synthesized in response to physiological need for NOsynthase enzyme from its metabolic precursor amino acids L-arginine, (Hirst and Robson, 2011).Currently, NO is considered as a signal molecule of the digestive system, since it stimulates relaxation of the smooth muscles of the esophagus, ventricle, small and large bowels, gall bladder, sphincter of ampulla of the pancreaticobiliary channel (Oddi) (Glemens, 1999;Leung Tung-Ming, Tipoe, Liong et al., 2010). Under physiological conditions, the endogenous NO -one of the mediators of exocrine pancreas secretion and mucin-producing cells of the gastric mucosa and bowels, stability, nonspecific and specific mucosal protection from the action of internal and external corrosive enviro...

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Nitric oxide in liver injury

Cited by 179 publications

References 81 publications

Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells

Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells

Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning

State of Gastric Mucosa and Small Intestine Nitro-Ergic System During Chronic Heliotrine-Induced Hepatitis

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