Protective effects of somatostatin against gastric damage induced by hemorrhagic shock, stress and PAF in the rat

Fluid resuscitation could hardly be performed immediately after fatal hemorrhagic shock in outpatients. We investigated whether electroacupuncture (EA) at Zusanli (ST36) could prevent fatal hemorrhagic shock induced heart failure with delayed fluid resuscitation and whether the protective role of EA is related to the autonomic nervous system. Sixty Sprague Dawley rats were randomly divided into five groups (n=12 each): group of sham hemorrhagic shock (SHAM), group of EA, group of sham EA (SEA), group of delayed fluid resuscitation with EA (EA + DR), and group of delayed fluid resuscitation with SEA (SEA + DR). After blood loss for 6 hours, caspase-3 activity and positive rate of TUNEL in EA + DR group were significantly lower than in other hemorrhagic shock groups (e.g., versus SEA + DR: 0.156±0.039 versus 0.301±0.042; P<0.05). Immediately EA treatment after the blood loss enhanced the protective effect of delayed resuscitation on the cardiac tissue of hemorrhagic shock rats. Considering the significant changes of epinephrine (137.8±6.9 ng/L versus 98.6±7.4 ng/L; P<0.05) and acetylcholine (405±8.6 pmol/L versus 341±10.1 pmol/L; P<0.05) after EA treatment (SEA + DR versus EA + DR), this cardiac protective effect may be related to regulation of the autonomic nervous system.

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Aspirin, but not NO-releasing aspirin (NCX-4016), interacts with selective COX-2 inhibitors to aggravate gastric damage and inflammation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00295.2003 ◽

2004 ◽

Vol 286 (1) ◽

pp. G76-G81 ◽

Cited By ~ 33

Author(s):

John L. Wallace ◽

Stella R. Zamuner ◽

Webb McKnight ◽

Michael Dicay ◽

Andrea Mencarelli ◽

...

Keyword(s):

Repeated Administration ◽

Mucosal Injury ◽

Gastric Damage ◽

Attractive Alternative ◽

Myeloperoxidase Activity ◽

Protective Effects ◽

Cox 2 ◽

Nitric Oxide Releasing ◽

Cox 2 Inhibitors ◽

Ncx 4016

Aceylation of cyclooxygenase (COX)-2 by aspirin can trigger the formation of 15(R)-epilipoxin A4, or aspirin-triggered lipoxin (ATL). ATL exerts protective effects in the stomach. Selective COX-2 inhibitors block ATL synthesis and exacerbate aspirin-induced gastric damage. Nitric oxide-releasing aspirins, including NCX-4016, have antiplatelet effects similar to aspirin but do not cause gastric damage. In the present study, we examined whether or not NCX-4016 triggers ATL synthesis and/or upregulates gastric COX-2 expression and the effects of coadministration of NCX-4016 with a selective COX-2 inhibitor on gastric mucosal injury and inflammation. Rats were given aspirin or NCX-4016 orally and either vehicle or a selective COX-2 inhibitor (celecoxib) intraperitoneally. Gastric damage was blindly scored, and granulocyte infiltration into gastric tissue was monitored through measurement of myeloperoxidase activity. Gastric PG and ATL synthesis was measured as was COX-2 expression. Whereas celecoxib inhibited gastric ATL synthesis and increased the severity of aspirin-induced gastric damage and inflammation, coadministration of celecoxib and NCX-4016 did not result in damage or inflammation. NCX-4016 did not upregulate gastric COX-2 expression nor did it trigger ATL synthesis (in contrast to aspirin). Daily administration of aspirin for 5 days resulted in significantly less gastric damage than that seen with a single dose, as well as augmented ATL synthesis. Celecoxib reversed this effect. In contrast, repeated administration of NCX-4016 failed to cause gastric damage, whether given alone or with celecoxib. These studies support the notion that NCX-4016 may be an attractive alternative to aspirin for indications such as cardioprotection, including in individuals also taking selective COX-2 inhibitors.

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Mechanistic evaluation of gastro-protective effects of KangFuXinYe on indomethacin-induced gastric damage in rats

Chinese Journal of Natural Medicines ◽

10.1016/s1875-5364(20)30004-2 ◽

2020 ◽

Vol 18 (1) ◽

pp. 47-56

Author(s):

Qi-Juan LI ◽

Zhan-Guo WANG ◽

Yu XIE ◽

Qiao LIU ◽

Hui-Ling HU ◽

...

Keyword(s):

Gastric Damage ◽

Protective Effects

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Platelet-activating factor mediates gastric damage induced by hemorrhagic shock

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.1.g140 ◽

1990 ◽

Vol 259 (1) ◽

pp. G140-G146 ◽

Cited By ~ 3

Author(s):

J. L. Wallace ◽

C. M. Hogaboam ◽

G. W. McKnight

Keyword(s):

Hemorrhagic Shock ◽

Marked Decrease ◽

Ex Vivo ◽

Platelet Activating Factor ◽

Gastric Damage ◽

Doppler Flowmetry ◽

Shed Blood ◽

Arterial Blood ◽

Gastric Lumen

The role of platelet-activating factor (PAF) as a mediator of the gastric damage associated with hemorrhagic shock was investigated using a rat model. With use of an ex vivo gastric chamber preparation, the gastric mucosa was bathed with 0.1 M HCl for 90 min. At minute 10 the systemic arterial blood pressure (BP) was reduced to 25 mmHg by bleeding from the femoral artery. BP was maintained at this level for 15 min, then the shed blood was reinfused. In control rats subjected to this protocol, extensive gastric damage developed during and after the shock period and involved an average of 50 +/- 8% of the total area of glandular mucosa. A marked decrease in transmucosal potential difference (PD) was observed during shock, with little recovery thereafter. Also, significant appearance of protein and hemoglobin (Hb) in the gastric lumen was detected after induction of shock. Oral pretreatment of the rats with the PAF antagonist WEB 2086 (0.5-20 mg/kg) dose dependently reduced the extent of macroscopically visible gastric damage, the decrease in transmucosal PD, and the appearance in the lumen of protein and Hb. A similar protective effect was observed with another PAF antagonist, BN 52021 (10 mg/kg). With use of laser-Doppler flowmetry, changes in gastric blood flow were determined before, during, and after induction of shock.(ABSTRACT TRUNCATED AT 250 WORDS)

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Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: role of neutrophils

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.273.6.g1246 ◽

1997 ◽

Vol 273 (6) ◽

pp. G1246-G1251 ◽

Cited By ~ 17

Author(s):

John L. Wallace ◽

Webb McKnight ◽

Tammy L. Wilson ◽

Piero Del Soldato ◽

Giuseppe Cirino

Keyword(s):

Nitric Oxide ◽

Hemorrhagic Shock ◽

Gastric Damage ◽

Leukocyte Adherence ◽

Inhibitory Effects ◽

Neutrophil Adherence ◽

Nitric Oxide Releasing ◽

Derivatives Of ◽

Ncx 4016

The gastric damage associated with hemorrhagic shock appears to occur, at least in part, through neutrophil-dependent mechanisms. Nitric oxide (NO)-releasing derivatives of aspirin have been shown to spare the gastrointestinal tract of injury. As NO can inhibit neutrophil adherence, it is possible that such a derivative of aspirin (NCX-4016) would exert inhibitory effects on neutrophil adherence and therefore be capable of protecting the stomach against shock-induced gastric damage. This hypothesis was tested in this study. Oral administration of NCX-4016 or glyceryl trinitrate or depletion of circulating neutrophils with antineutrophil serum significantly reduced the extent of gastric damage induced by hemorrhagic shock, whereas aspirin had no effect. NCX-4016 and antineutrophil serum pretreatment resulted in significant preservation of gastric blood flow during the shock period. Moreover, NCX-4016, but not aspirin, was capable of inhibiting N-formyl-Met-Leu-Phe-induced leukocyte adherence to postcapillary mesenteric venules. These results suggest that an NO-releasing aspirin derivative reduces the susceptibility of the stomach to shock-induced damage through inhibitory effects on neutrophil adherence to the vascular endothelium.

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