Effect of Aminoguanidine on Ischemia/Reperfusion Injury in Rat Small Intestine

Takizawa, Yusuke; Kitazato, Takuya; Ishizaka, Haruka; Kamiya, Naomi; Tomita, Mikio; Hayashi, Masahiro

doi:10.1248/bpb.34.1737

Cited by 11 publications

(6 citation statements)

References 32 publications

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“…However, excessive NO production through NOS2 has been proved to be detrimental in the pathogenesis of intestinal I/R (40). Suppression of excessive NO production using various NO inhibitors has beneficial effects on ameliorating intestinal I/R injury (41,42). In the current study, intestinal I/R resulted in severe intestine damage and delayed intestine repair, as evidenced by the increase in modified Chiu scores and decrease in villus height.…”

Section: Discussionmentioning

confidence: 56%

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Liu

Wen

Zhan

et al. 2015

The Journal of Immunology

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Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B–like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2–M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition.

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Section: Discussionmentioning

confidence: 56%

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Liu

Wen

Zhan

et al. 2015

The Journal of Immunology

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“…In epithelial cells of the gastrointestinal tract, NO has been shown to both increase and decrease permeability 20-23, 41-45 . The precise explanation for these data is unclear; however it may be related to the source of the NO, and therefore its concentration.…”

Section: Discussionmentioning

confidence: 99%

“…Most studies in which constitutive NO synthases (cNOSs), including neuronal NO synthase (nNOS) and endothelial NO synthase (eNOS), report that NO decrease permeability 46 . In contrast, when inducible NO synthase (iNOS) is activated, NO appears to increase permeability 20-22, 45, 46 . It is known that cNOSs produce low, levels of NO while iNOS is a high output enzyme involved in pathophysiological disorders 47, 48 .…”

Section: Discussionmentioning

confidence: 99%

“…NO has also been shown to reduce the assembly of the proteins that form the paracellular pathway of Sertoli cells via a cGMP and PKG-dependent process 19 . Finally, in intestinal epithelial cells NO has been reported to both increase and decrease total permeability and permselectivity of the paracellular pathway in both physiological and pathological states 20-24 .…”

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confidence: 99%

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Nitric Oxide Decreases the Permselectivity of the Paracellular Pathway in Thick Ascending Limbs

Monzón

Garvin

2015

Hypertension

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Thick ascending limbs (THALs) reabsorb 25–30% of the filtered NaCl. About 50–70% is reabsorbed via the transcellular pathway and 30–50% is reabsorbed through the Na-selective paracellular pathway. Nitric oxide (NO) inhibits transepithelial Na reabsorption, but its effects on the paracellular pathway are unknown. We hypothesized that NO decreases the selectivity of the paracellular pathway in THALs via cGMP-dependent protein kinase (PKG). To assess relative Na/Cl permeability ratios (PNa/PCl), we perfused rat THALs and measured the effect of reducing bath NaCl on transepithelial voltage, creating dilution potentials, with vehicle, NO donors and endogenous NO. PNa/PCl was calculated using the Goldman-Hodgkin-Katz equation. Reducing bath Na/Cl to 16/8; 32/24; and 64/56 mmol/l created dilution potentials of −13.6 ± 2.2, −10.8 ± 3.0, and −6.1 ± 0.9 mV, respectively. Calculated PNa/PCls were 2.0 ± 0.2, 2.2 ± 0.5, and 1.9 ± 0.2. The NO donor spermine NONOate (SPM; 200 μmol/l) blunted the dilution potential caused by 32/24 mmol/l Na/Cl from −11.1 ± 2.1 to −6.5 ± 1.6 mV (p<0.004) and PNa/PCl from 2.2 ± 0.4 to 1.5± 0.2. Nitroglycerin (200 μmol/l), another NO donor, also reduced PNa/PCl. Controls showed no significant changes. Dibutyryl-cGMP decreased dilution potentials from −13.4 ± 2.9 to −7.5 ± 1.8 mV (n=6, p<0.01). PKG inhibition with KT5823 (4μM) blocked the effect of SPM, while phosphodiesterase 2 inhibition did not. Endogenously-produced NO mimicked the effect of the NO donors. Conclusion: NO reduces the selectivity of the paracellular pathway in thick ascending limbs via cGMP and PKG.

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“…Furthermore, NO induces the formation of vermiculite mucosa in the intestinal tract. NO is postulated to be a cytotoxic factor, similar to free radicals, which plays a role in pathophysiological processes, including various forms of inflammation and circulatory shock [16].…”

mentioning

confidence: 99%

Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats

Barut¹,

Özaçmak²,

TURAN³

et al. 2016

CIM

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Purpose: Multiple organ failure, including acute lung injury, is a common complication of intestinal ischemia and reperfusion (I/R) injury and contributes to its high mortality rate. Activated polymorphonuclear neutrophils and reactive oxygen species contribute to the lung injury caused by intestinal I/R. Mineralokortikoid receptor antagonist spironolactone has a protective effect against I/R injury in animal models of retina, kidney, heart, and brain. The aim of the present study is to investigate the effect of aldosteron receptor blocker spironolactone on lung injury induced by intestinal I/R.Methods: Wistar albino rats were divided into four groups: (1) sham control; (2) intestinal I/R (30 min of ischemia by superior mesenteric artery occlusion followed by 3 h of reperfusion); (3) spironolactone pretreatment (20 mg/kg) + I/R; and, (4) spironolactone pretreatment without I/R. Spironolactone was given orally 3 days prior to intestinal I/R. A marker for lipid peroxidation (malondialdehyde; MDA), an indicator or oxidation state (reduced glutathione; GSH), an index of polymorphonuclear neutrophil sequestration (myeloperoxidase; MPO), inducible nitric oxide synthase (iNOS) immunoreactivity, and the histopathology of the lung tissue were analyzed.Results: Spironolactone pretreatment markedly reduced intestinal I/R-induced lung injury as indicated by histology and MDA and MPO levels. Moreover, the pretreatment decreased the iNOS immunoreactivity. Conclusion:The present study strongly suggests that spironolactone pretreatment decreased neutrophil infiltration, iNOS induction, oxidative stress, and histopathological injury in an experimental model of intestinal I/R induced-lung injury of rats.

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Effect of Aminoguanidine on Ischemia/Reperfusion Injury in Rat Small Intestine

Cited by 11 publications

References 32 publications

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Nitric Oxide Decreases the Permselectivity of the Paracellular Pathway in Thick Ascending Limbs

Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats

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