scholarly journals Anti-inflammatory effects of angiotensin II AT1 receptor antagonism prevent stress-induced gastric injury

2003 ◽  
Vol 285 (2) ◽  
pp. G414-G423 ◽  
Author(s):  
Claudia Bregonzio ◽  
Ines Armando ◽  
Hiromichi Ando ◽  
Miroslava Jezova ◽  
Gustavo Baiardi ◽  
...  

Stress reduces gastric blood flow and produces acute gastric mucosal lesions. We studied the role of angiotensin II in gastric blood flow and gastric ulceration during stress. Spontaneously hypertensive rats were pretreated for 14 days with the AT1 receptor antagonist candesartan before cold-restraint stress. AT1 receptors were localized in the endothelium of arteries in the gastric mucosa and in all gastric layers. AT1 blockade increased gastric blood flow by 40–50%, prevented gastric ulcer formation by 70–80% after cold-restraint stress, reduced the increase in adrenomedullary epinephrine and tyrosine hydroxylase mRNA without preventing the stress-induced increase in adrenal corticosterone, decreased the stress-induced expression of TNF-α and that of the adhesion protein ICAM-1 in arterial endothelium, decreased the neutrophil infiltration in the gastric mucosa, and decreased the gastric content of PGE2. AT1 receptor blockers prevent stress-induced ulcerations by a combination of gastric blood flow protection, decreased sympathoadrenal activation, and anti-inflammatory effects (with reduction in TNF-α and ICAM-1 expression leading to reduced neutrophil infiltration) while maintaining the protective glucocorticoid effects and PGE2 release. Angiotensin II has a crucial role, through stimulation of AT1 receptors, in the production and progression of stress-induced gastric injury, and AT1 receptor antagonists could be of therapeutic benefit.

2021 ◽  
Vol 22 (10) ◽  
pp. 5211
Author(s):  
Dominik Bakalarz ◽  
Edyta Korbut ◽  
Zhengnan Yuan ◽  
Bingchen Yu ◽  
Dagmara Wójcik ◽  
...  

Hydrogen sulfide (H2S) is an endogenously produced molecule with anti-inflammatory and cytoprotective properties. We aimed to investigate for the first time if a novel, esterase-sensitive H2S-prodrug, BW-HS-101 with the ability to release H2S in a controllable manner, prevents gastric mucosa against acetylsalicylic acid-induced gastropathy on microscopic and molecular levels. Wistar rats were pretreated intragastrically with vehicle, BW-HS-101 (0.5–50 μmol/kg) or its analogue without the ability to release H2S, BW-iHS-101 prior to ASA administration (125 mg/kg, intragastrically). BW-HS-101 was administered alone or in combination with nitroarginine (L-NNA, 20 mg/kg, intraperitoneally) or zinc protoporphyrin IX (10 mg/kg, intraperitoneally). Gastroprotective effects of BW-HS-101 were additionally evaluated against necrotic damage induced by intragastrical administration of 75% ethanol. Gastric mucosal damage was assessed microscopically, and gastric blood flow was determined by laser flowmetry. Gastric mucosal DNA oxidation and PGE2 concentration were assessed by ELISA. Serum and/or gastric protein concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, VEGF, GM-CSF, IFN-γ, TNF-α, and EGF were determined by a microbeads/fluorescent-based multiplex assay. Changes in gastric mucosal iNOS, HMOX-1, SOCS3, IL1-R1, IL1-R2, TNF-R2, COX-1, and COX-2 mRNA were assessed by real-time PCR. BW-HS-101 or BW-iHS-101 applied at a dose of 50 μmol/kg protected gastric mucosa against ASA-induced gastric damage and prevented a decrease in the gastric blood flow level. H2S prodrug decreased DNA oxidation, systemic and gastric mucosal inflammation with accompanied upregulation of SOCS3, and EGF and HMOX-1 expression. Pharmacological inhibition of nitric oxide (NO) synthase but not carbon monoxide (CO)/heme oxygenase (HMOX) activity by L-NNA or ZnPP, respectively, reversed the gastroprotective effect of BW-HS-101. BW-HS-101 also protected against ethanol-induced gastric injury formation. We conclude that BW-HS-101, due to its ability to release H2S in a controllable manner, prevents gastric mucosa against drugs-induced gastropathy, inflammation and DNA oxidation, and upregulate gastric microcirculation. Gastroprotective effects of this H2S prodrug involves endogenous NO but not CO activity and could be mediated by cytoprotective and anti-inflammatory SOCS3 and EGF pathways.


2004 ◽  
Vol 5 (1) ◽  
pp. 28-34 ◽  
Author(s):  
Yi Min Duan ◽  
Zhao Shen Li ◽  
Xian Bao Zhan ◽  
Guo Ming Xu ◽  
Zhen Xing Tu ◽  
...  

2004 ◽  
Vol 1018 (1) ◽  
pp. 351-355 ◽  
Author(s):  
C BREGONZIO ◽  
I ARMANDO ◽  
H ANDO ◽  
M JEZOVA ◽  
G BAIARDI ◽  
...  

2020 ◽  
Vol 6 (2) ◽  
pp. 100-110
Author(s):  
Despoina Kakagia ◽  
Apostolos Papalois ◽  
Maria Lambropoulou ◽  
Fotini Papachristou ◽  
Gregory Trypsiannis ◽  
...  

AbstractIntroductionPeptic mucosal damage induced by acute stress is a serious cause of morbidity and mortality in critically ill patients. The study aimed to investigate the protective, antioxidant and anti-inflammatory effects of pretreatment with Chios mastic gum (CMG), a traditionally consumed herbal resin naturally deriving from the trunk of Pistacia Lentiscus var. Chia compared to Omeprazole, a standard medication used in the prevention and treatment of gastritis, against the effects of cold restraint stress (CRS) in rat gastric and colonic mucosa.MethodsTwenty-one male Wistar rats were randomly assigned to three groups: Control (C), Omeprazole (O), and CMG (M), according to the pre-treatment regime, and were subjected to CRS at 40C for 3 hours. The gastric and colonic mucosal lesions were histologically assessed. ELISA measured blood concentrations of TNF-α, IL-1β, peroxidase, superoxide dismutase (SOD) and total antioxidant capacity (TEAC).ResultsIn both groups, O and M, gastric mucosal hyperemia, haemorrhagic infiltration and mucosal oedema, as well as colonic mucosal hyperaemia and haemorrhagic infiltration were significantly reduced compared to the controls (p<0.05). No significant differences were observed between Groups O and M. TNF-α levels were significantly lower in group M compared to Group O (p=0.013). IL-1β levels were significantly depressed in groups M and O compared to control (p≤ 0.001). The activity of both peroxidase and SOD enzymes decreased in group M compared to group O (p= 0.043 and p=0.047 respectively) and the control (p=0.018 and p< 0.001 respectively).ConclusionsThe natural Chios mastic gum is a promising nutritional supplement with protective properties to the peptic mucosa against CRS, exerting anti-inflammatory and antioxidant effects.


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