Ethanol-induced injury to the rat gastric mucosa

Kvietys, Peter R.; Twohig, B.; Danzell, Jerome; Specian, Robert D.

doi:10.1016/0016-5085(90)90015-s

Cited by 168 publications

(33 citation statements)

References 30 publications

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“…Neutrophil adherence to endothelial cells is now considered as an important component of vascular damage within the gastrointestinal microcirculation, including the mucosal injury induced by haemorrhagic shock or ischaemia-reperfusion, as well as that following the administration of PAF, ethanol or non-steroid anti-inflammatory agents (Smith et al, 1987;Hernandez et al, 1987;Granger et al, 1989;Kubes et al, 1990a,b;Kvietys et al, 1990;Wallace et al, 1990;. Adherence of such inflammatory cells to the endothelium, which is promoted by the expression of adhesion molecules on both neutrophils and endothelial cells (see Springer, 1990;Zimmerman et al, 1992 for review), can lead to the local release of cytotoxic mediators, including oxygen radicals (Grisham & Granger, 1988), known to provoke microvascular injury (Parks & Granger, 1983;Parks et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

Time‐dependent enhancement or inhibition of endotoxin‐induced vascular injury in rat intestine by nitric oxide synthase inhibitors

László

Whittle

Moncada

1994

British J Pharmacology

135

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1 The effects of the nitric oxide (NO) synthase inhibitors, N0-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), on the vascular damage induced by the endotoxin, E. coli lipopolysaccharide (LPS), in the ileum and colon were investigated in the conscious rat over a 5 h period. 2 Administration of LPS (3 mg kg-', i.v.) increased ileal and colonic vascular injury after a lag period of 2 h, as determined by the leakage of radiolabelled albumin. 3 Administration of L-NAME (1-5 mg kg-', s.c.) concurrently with LPS, produced a dose-dependent increase in vascular albumin leakage in the intestinal tissues, when determined over a 5 h period. Vascular albumin leakage with LPS and L-NAME (5 mg kg-') was substantially increased after 1 h, reached maximal levels 3 h after administration, and then slowly declined. 4 L-NMMA (50 mg kg-1, s.c.), likewise elevated intestinal albumin leakage when administered concurrently with LPS, but this reached maximal levels after 1 h and rapidly declined over the subsequent 2 h. 5 In control rats, in the absence of LPS challenge, neither L-NAME (5 mg kg-', s.c.) nor L-NMMA (50 mg kg-', s.c.) increased intestinal vascular leakage of albumin over a 5 h period. 6 By contrast, when L-NAME (1-5 mg kg-', s.c.) or L-NMMA (12.5-50mg kg-', s.c.) was injected 3 h after LPS, a dose-dependent reduction in the LPS-provoked vascular albumin leakage was observed. 7 Pretreatment with L-arginine (300 mg kg-', s.c.) 15 min prior to the NO synthase inhibitors, reversed either the potentiation or the inhibition by L-NAME (5 mg kg-', s.c.) or L-NMMA (50 mg kg-', s.c.) of the LPS-induced intestinal vascular damage. 8 These findings indicate that initial suppression of the constitutive NO synthase by L-NAME or L-NMMA following challenge with LPS aggravates the acute vascular injury in the ileum and colon, suggesting a defensive role of NO. By contrast, the delayed administration of NO synthase inhibitors, at a time of known expression of the inducible NO synthase, provides protection against the subsequent damage to the intestinal vasculature.

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Section: Discussionmentioning

confidence: 99%

Time‐dependent enhancement or inhibition of endotoxin‐induced vascular injury in rat intestine by nitric oxide synthase inhibitors

László

Whittle

Moncada

1994

British J Pharmacology

135

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“…T here is growing evidence that lipid peroxidation (LP) could play a significant role in the pathogenesis of ethanol-induced gastric mucosal lesions, especially because oxygen radicals have been directly implicated in the damage of cell membranes after administration of that agent (Kvietys et al, 1990;Szelenyi and Brune, 1988;Terano et al, 1989). Indeed, the hypothesis that superoxide free radicals are involved in the immediate deleterious effect of ethanol on gastric mucosa seems to be confirmed by these studies.…”

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confidence: 94%

Gastric Mucosal Cell Proliferation in Ethanol-Induced Chronic Mucosal Injury Is Related to Oxidative Stress and Lipid Peroxidation in Rats

Hernández‐Muñoz

Montiel-Ruíz

Vázquez‐Martínez

2000

Laboratory Investigation

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SUMMARY:The oxygen free radicals-induced lipid peroxidation (LP) has been implicated in the pathogenesis of acute ethanol-induced gastric mucosal lesions. However, the role of LP in the generation of chronic gastric mucosal injury is unknown. We have developed a model of chronic mucosal injury induced by continuous ethanol ingestion for 5 days and characterized by marked alterations in plasma membranes from gastric mucosa. Therefore, LP was evaluated in this experimental model. Indicators of peroxidative activity, mucosal glutathione content, thymidine kinase activity (an index of cell proliferation), and histamine H 2 -receptor (H 2 R) binding constants were quantified in animals undergoing gastric mucosal damage. The effect of famotidine, a H 2 R antagonist that readily ameliorates the chronic mucosal injury, was also tested. Increased free radicals and LP levels were detected during gastritis; however, a second, higher peak of LP was noted in mucosal plasma membranes after ethanol withdrawal (recovery period). This further increase of LP coincided with active cell proliferation, decreased mucosal glutathione levels, and diminished specific cimetidine binding by H 2 R. Administration of famotidine accelerated the mucosal proliferative process, inducing the second lipoperoxidative episode sooner, and preserved the content of glutathione. In addition, LP correlated directly with cell proliferation and inversely with mucosal membrane cimetidine binding. In conclusion, LP seems to be involved in chronic ethanol-induced gastric mucosal injury. However, a further enhancement of plasma membrane LP occurred, associated with increased DNA synthesis and diminished cimetidine binding by membrane H 2 R. Therefore, increased LP could also participate in the compensatory mucosal proliferation initiated after ethanol withdrawal. (Lab Invest 2000, 80:1161-1169.

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“…Administration of an anti-neutrophil serum protects the intestinal mucosa against ischaemia-reperfusion and indomethacin-induced damage (Hernandez et al, 1987;Chmaisse et al, 1994) and reduces the susceptibility of the gastric mucosa to injury by ethanol (Kvietys et al, 1990;Tepperman et al, 1993), indomethacin (Wallace et al, 1990) or PAF (Etienne et al, 1988). The involvement of neutrophils in at least part of the intestinal vascular injury in the current acute model is suggested by the findings that the administration of an anti-neutrophil serum significantly inhibited the microvascular leakage.…”

Section: Discussionmentioning

confidence: 69%

“…One such mechanism could involve inhibition of neutrophil-dependent vascular endothelial damage, since in addition to being a vasodilator (Moncada et al, 1991), NO can attenuate the aggregation of neutrophils and their adhesion to the microvasculature (McCall et al, 1988;Kubes & Granger, 1992) as can SNAP (Xin-Liang et al, 1993). Exposure to PAF or endotoxin enhances the adherence of neutrophils to the endothelium (Matsuda et al, 1991;Koltai et al, 1991;Worthen et al, 1992) and such leukocytes play a key role in the elevation of vascular permeability during inflammation (Wedmore & Williams, 1981). Moreover, neutrophils are considered to be involved in the evolution of microvascular injury of the gut under acute pathological conditions (Hernandez et al, 1987;Kvietys et al, 1990;Chmaisse et al, 1994). During the development of such acute microvascular damage, neutrophils adhere to the vascular endothelium, releasing cytotoxic agents such as oxygen radicals and pro-inflammatory mediators including PAF (Sacks et al, 1978;Pabst & Johnston, 1980;Tauber & Babior, 1985;Hernandez et al, 1987;Kubes et al, 1990; .…”

Section: Discussionmentioning

confidence: 99%

Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat

László

Whittle

Moncada

1995

British J Pharmacology

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1 The effects of the nitric oxide (NO) donors, S-nitroso-glutathione (SNOG) and S-nitroso-N-acetylpenicillamine (SNAP), on the acute intestinal microvascular dysfunction induced by N'-nitro-L-arginine methyl ester (L-NAME) in combination with low doses of endotoxin were investigated in the anaesthetized rat. 2 Administration of L-NAME (5 mg kg', s.c.) concurrently with E. coli lipopolysaccharide (LPS, 3 mg kg-1, i.v.) provoked the leakage of radiolabelled albumin in the ileum and colon, as a measure of microvascular damage, determined 1 h after challenge.3 Intravenous infusion of SNOG or SNAP (1-lOpgkg-'min'1) dose-dependently attenuated the microvascular leakage induced by L-NAME and LPS.4 Infusion of the lowest doses of SNOG or SNAP (1 jig kg-' min', i.v.) that significantly reduced the albumin leakage, did not affect the increase in blood pressure in response to L-NAME in LPS-treated rats. Higher doses of SNOG or SNAP (5-I0lg kg-' min', i.v.) dose-dependently reduced this increase in blood pressure.5 In control studies, intravenous infusion of glutathione (10fig kg-' min-') or N-acetyl-penicillamine (I0 ig kg-l minm) had no effect on microvascular leakage in the ileum and colon induced by LPS and L-NAME.6 Pretreatment with rabbit anti-rat neutrophil serum (0.4 ml kg-', i.p., 4 h before challenge), which reduced the neutrophil count in peripheral arterial blood, also inhibited the microvascular leakage in the ileum and colon. 7 The protective effects of the nitrosothiol NO donors in this model may reflect, in part, modulation of neutrophil interactions within the microcirculation or actions on endothelial cell integrity, in addition to any local vasodilator action.

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Ethanol-induced injury to the rat gastric mucosa

Cited by 168 publications

References 30 publications

Time‐dependent enhancement or inhibition of endotoxin‐induced vascular injury in rat intestine by nitric oxide synthase inhibitors

Time‐dependent enhancement or inhibition of endotoxin‐induced vascular injury in rat intestine by nitric oxide synthase inhibitors

Gastric Mucosal Cell Proliferation in Ethanol-Induced Chronic Mucosal Injury Is Related to Oxidative Stress and Lipid Peroxidation in Rats

Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat

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