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10.1038/s41598-018-22727-6

http://scihub22266oqcxt.onion/10.1038/s41598-018-22727-6
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suck abstract from ncbi


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pmid29523851
      Sci+Rep 2018 ; 8 (1 ): 4280
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  • A Novel Role of Irbesartan in Gastroprotection against Indomethacin-Induced Gastric Injury in Rats: Targeting DDAH/ADMA and EGFR/ERK Signaling #MMPMID29523851
  • Shahin NN ; Abdelkader NF ; Safar MM
  • Sci Rep 2018[Mar]; 8 (1 ): 4280 PMID29523851 show ga
  • The advent of angiotensin II type 1 receptor blockers (ARBs) as intriguing gastroprotective candidates and the superior pharmacokinetics and pharmacodynamics displayed by irbesartan compared to many other ARBs raised the interest to investigate its gastroprotective potential in a rat model of gastric injury. Irbesartan (50?mg/Kg) was orally administered to male Wistar rats once daily for 14 days; thereafter gastric injury was induced by indomethacin (60?mg/Kg, p.o). Irbesartan reduced gastric ulcer index, gastric acidity, and ameliorated indomethacin-induced gastric mucosal apoptotic and inflammatory aberrations, as demonstrated by hampering caspase-3, prostaglandin E(2) and tumor necrosis factor-alpha levels and cyclooxygenase-2 mRNA expression. This ARB increased mucosal dimethylarginine dimethylaminohydrolase-1 (DDAH-1) gene expression and decreased elevated levels of matrix metalloproteinase-9, asymmetric dimethylarginine (ADMA), epidermal growth factor receptor (EGFR) mRNA and phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Histopathological evaluation corroborated biochemical findings. Overall efficacy of irbesartan was comparable to ranitidine, the widely used H(2) receptor blocker. In conclusion, irbesartan exerts significant gastroprotection against indomethacin-induced mucosal damage via acid-inhibitory, anti-inflammatory, anti-apoptotic and extracellular matrix remodeling mechanisms that are probably mediated, at least partly, by down-regulating DDAH/ADMA and EGFR/ERK1/2 signaling.
  • |*MAP Kinase Signaling System [MESH]
  • |Amidohydrolases/*metabolism [MESH]
  • |Animals [MESH]
  • |Anti-Inflammatory Agents/*pharmacology/therapeutic use [MESH]
  • |Apoptosis [MESH]
  • |Arginine/*analogs & derivatives/metabolism [MESH]
  • |Extracellular Matrix/drug effects/metabolism [MESH]
  • |Gastric Mucosa/drug effects/metabolism [MESH]
  • |Indomethacin/toxicity [MESH]
  • |Irbesartan/*pharmacology/therapeutic use [MESH]
  • |Male [MESH]
  • |Matrix Metalloproteinase 9/metabolism [MESH]
  • |Mitogen-Activated Protein Kinase 1/metabolism [MESH]
  • |Mitogen-Activated Protein Kinase 3/metabolism [MESH]
  • |Peptic Ulcer/*drug therapy/etiology/metabolism [MESH]
  • |Rats [MESH]


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