Inhibition of endogenous CO by ZnPP protects against stress-induced gastric lesion in adult male albino rats

Ibrahim, Ibrahim; Elsayed, Salah Eldin; Abdel-Hakim, Selim; Hassan, Magdy K.; Aziz, Neven Makram

doi:10.1007/s13105-011-0143-x

Cited by 9 publications

(6 citation statements)

References 50 publications

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“…These conclusions were made despite the apparent inhibition of endogenous CO by ZnPP, while zinc has been shown to exert gastroprotective and anti-ulcer effects. This discrepancy between our results and their observation [ 42 ] may be due to different experimental conditions. Such difference include the combined method of stress induction with the use of pylorus ligating for assessment of gastric acid secretion and exposure to cold stress along with an experimental design, which included chronic (10 days) administration of this HO inhibitor [ 42 ] vs. the application of ZnPP in a single dose prior to stress exposure in our present work.…”

Section: Discussioncontrasting

confidence: 99%

“…further enhanced this effect in gastric mucosa compromised by WRS. Similarly to our results, both Morsy et al and Ibrahim et al reported an increase in gastric HO-1 expression in response to cold stress as determined by immunohistochemistry or enzyme-linked immunosorbent assay (ELISA), respectively [ 42 , 43 ]. We observed that the HO-1 inducer, hemin, in the highest dose (10 mg/kg i.g.…”

Section: Discussionsupporting

confidence: 90%

“…Our finding support the notion that CORM-2 in the protective dose used was not sufficient to counteract the deficit in CO content resulting from the inhibition of HO by ZnPP. However, our observations using ZnPP in the stress-injured rat stomach seem to be at variance with those by Ibrahim et al [ 42 ] who reported that 10 days of ZnPP administration reduced stress-induced gastric lesions. They had also concluded that the protective effect of ZnPP against gastric ulcers induced by cold stress might be related to an inhibition of gastric acidity and the availability of zinc from this HO inhibitor.…”

Section: Discussioncontrasting

confidence: 87%

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The Protective Role of Carbon Monoxide (CO) Produced by Heme Oxygenases and Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress-Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO)

Magierowska

Magierowski

Surmiak

et al. 2016

IJMS

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Carbon monoxide (CO) produced by heme oxygenase (HO)-1 and HO-2 or released from the CO-donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) causes vasodilation, with unknown efficacy against stress-induced gastric lesions. We studied whether pretreatment with CORM-2 (0.1–10 mg/kg oral gavage (i.g.)), RuCl3 (1 mg/kg i.g.), zinc protoporphyrin IX (ZnPP) (10 mg/kg intraperitoneally (i.p.)), hemin (1–10 mg/kg i.g.) and CORM-2 (1 mg/kg i.g.) combined with NG-nitro-l-arginine (l-NNA, 20 mg/kg i.p.), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 mg/kg i.p.), indomethacin (5 mg/kg i.p.), SC-560 (5 mg/kg i.g.), and celecoxib (10 mg/kg i.g.) affects gastric lesions following 3.5 h of water immersion and restraint stress (WRS). Gastric blood flow (GBF), the number of gastric lesions and gastric CO and nitric oxide (NO) contents, blood carboxyhemoglobin (COHb) level and the gastric expression of HO-1, HO-2, hypoxia inducible factor 1α (HIF-1α), tumor necrosis factor α (TNF-α), cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) were determined. CORM-2 (1 mg/kg i.g.) and hemin (10 mg/kg i.g.) significantly decreased WRS lesions while increasing GBF, however, RuCl3 was ineffective. The impact of CORM-2 was reversed by ZnPP, ODQ, indomethacin, SC-560 and celecoxib, but not by l-NNA. CORM-2 decreased NO and increased HO-1 expression and CO and COHb content, downregulated HIF-1α, as well as WRS-elevated COX-2 and iNOS mRNAs. Gastroprotection by CORM-2 and HO depends upon CO’s hyperemic and anti-inflammatory properties, but is independent of NO.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 90%

Section: Discussioncontrasting

confidence: 87%

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The Protective Role of Carbon Monoxide (CO) Produced by Heme Oxygenases and Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress-Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO)

Magierowska

Magierowski

Surmiak

et al. 2016

IJMS

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“…This suggests that ZnPPIX counteracting protective effect of CORM-2 against ethanol ulcerogenesis cannot be explained by inhibitory effect of ZnPPIX on HO-1 enzyme expression and the mechanism of action of this compound in the stomach injured by ethanol should be further investigated. In contrast, ZnPPIX has been shown to afford protection against hemorrhagic lesions induced by cold restraint stress through reduction of free and total acidity of gastric secretion and decreased lipid peroxidation [ 45 ]. This apparent difference in the effect of ZnPPIX against cold stress- and ethanol-induced gastric damage could be attributed, at least in part, to the different experimental models of gastric injury depending (stress) and not depending (ethanol) upon gastric acid studied in their [ 45 ] and our present study.…”

Section: Discussionmentioning

confidence: 99%

Carbon Monoxide (CO) Released from Tricarbonyldichlororuthenium (II) Dimer (CORM-2) in Gastroprotection against Experimental Ethanol-Induced Gastric Damage

et al. 2015

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The physiological gaseous molecule, carbon monoxide (CO) becomes a subject of extensive investigation due to its vasoactive activity throughout the body but its role in gastroprotection has been little investigated. We determined the mechanism of CO released from its donor tricarbonyldichlororuthenium (II) dimer (CORM-2) in protection of gastric mucosa against 75% ethanol-induced injury. Rats were pretreated with CORM-2 30 min prior to 75% ethanol with or without 1) non-selective (indomethacin) or selective cyclooxygenase (COX)-1 (SC-560) and COX-2 (celecoxib) inhibitors, 2) nitric oxide (NO) synthase inhibitor L-NNA, 3) ODQ, a soluble guanylyl cyclase (sGC) inhibitor, hemin, a heme oxygenase (HO)-1 inductor or zinc protoporphyrin IX (ZnPPIX), an inhibitor of HO-1 activity. The CO content in gastric mucosa and carboxyhemoglobin (COHb) level in blood was analyzed by gas chromatography. The gastric mucosal mRNA expression for HO-1, COX-1, COX-2, iNOS, IL-4, IL-1β was analyzed by real-time PCR while HO-1, HO-2 and Nrf2 protein expression was determined by Western Blot. Pretreatment with CORM-2 (0.5–10 mg/kg) dose-dependently attenuated ethanol-induced lesions and raised gastric blood flow (GBF) but large dose of 100 mg/kg was ineffective. CORM-2 (5 mg/kg and 50 mg/kg i.g.) significantly increased gastric mucosal CO content and whole blood COHb level. CORM-2-induced protection was reversed by indomethacin, SC-560 and significantly attenuated by celecoxib, ODQ and L-NNA. Hemin significantly reduced ethanol damage and raised GBF while ZnPPIX which exacerbated ethanol-induced injury inhibited CORM-2- and hemin-induced gastroprotection and the accompanying rise in GBF. CORM-2 significantly increased gastric mucosal HO-1 mRNA expression and decreased mRNA expression for iNOS, IL-1β, COX-1 and COX-2 but failed to affect HO-1 and Nrf2 protein expression decreased by ethanol. We conclude that CORM-2 released CO exerts gastroprotection against ethanol-induced gastric lesions involving an increase in gastric microcirculation mediated by sGC/cGMP, prostaglandins derived from COX-1, NO-NOS system and its anti-inflammatory properties.

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“…It was also found that the process of endogenous antioxidant/Phase II detoxification was initiated to protect against cellular and tissue injury, as evidenced by the expression of heme oxygenase-1 (HO-1) in liver and kidney tissues. In previous studies, the rats subjected to restraint stress for 3 h exhibited a significant increase in HO-1 expression in stomach [47] and the exposure of acute restraint stress for 6 h caused Nrf2 and HO-1 in rat's hippocampus remarkably increased [48].…”

Section: Discussionmentioning

confidence: 88%

Guangdong Herbal Tea Attenuates Restraint Stress-provoked Liver and Kidney Damage in Mice via Activation of the Nrf2/ARE Signaling Pathway

Mengjiao¹,

Gui-yuan²

2016

J Nutr Food Sci

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In the present work, we investigated the protective effects of Guangdong Herbal Tea (GHT) on liver and kidney damage induced by restraint stress in mice, and we explored the relationship between these effects and the Nrf2/ARE signaling pathway. Pretreatment with GHT prior to the exposure to restraint stress significantly prevented an increase in the serum levels of hepatic and kidney functional markers (ALT, AST and BUN), lipid peroxidation (MDA) and alleviated oxidative stress, as determined by glutathione content (GSH), Catalase (CAT) activity and Total Antioxidant Capacity (T-AOC) in the liver and kidney. Meanwhile, GHT-induced Nrf2/ARE signaling pathway activation was evidenced by Nrf2 translocation into the nucleus. Moreover, GHT up-regulated heme oxygenase-1 (HO-1). Taken together, these results suggest that the protective effects of GHT against liver and kidney damage induced by restraint stress may be due to its antioxidant capacity and the up-regulation of HO-1 via the Nrf2/ARE signaling pathway.

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Inhibition of endogenous CO by ZnPP protects against stress-induced gastric lesion in adult male albino rats

Cited by 9 publications

References 50 publications

The Protective Role of Carbon Monoxide (CO) Produced by Heme Oxygenases and Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress-Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO)

The Protective Role of Carbon Monoxide (CO) Produced by Heme Oxygenases and Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress-Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO)

Carbon Monoxide (CO) Released from Tricarbonyldichlororuthenium (II) Dimer (CORM-2) in Gastroprotection against Experimental Ethanol-Induced Gastric Damage

Guangdong Herbal Tea Attenuates Restraint Stress-provoked Liver and Kidney Damage in Mice via Activation of the Nrf2/ARE Signaling Pathway

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