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Somatostatin effectively prevents ethanol-and NSAID-induced gastric mucosal damage in rats

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Abstract

The interrelationship between somatostatin and its synthetic analog, sandostatin, with neuropeptides and inflammatory mediators, as well as their protection of gastric mucosal damage, were tested in rats. Rats were treated intragastrically with 1.0 ml of 96% ethanol with or without intravenous or intraperitoneal coadministration of somatostatin (1.0 µM/kg). Mucosal damage was also induced by the administration of either indomethacin (30 mg/kg subcutaneously) with or without intravenous sandostatin (10 µg/rat), given 30 min prior to damage induction. Somatostatin levels in ethanol-damaged gastric mucosa were significantly lower than in control rats. Substance P and vasoactive intestinal peptide (VIP) levels were significantly higher in the damaged mucosa in rats treated with ethanol, as was the mucosal generation of leukotriene B4 (LTB4) and cysteinyl-containing leukotrienes. The coadministration of somatostatin with ethanol significantly reduced gastric mucosal injury induced by ethanol alone. The protection of the mucosa was accompanied by reduction of mucosal substance P and VIP levels, as well as the generation of leukotrienes, an effect that was reversed by intraperitoneal or intravenous coadministration of somatostatin antagonist, cyclo-(7-aminoheptanoyl-PH-E-d-Trp-Lys-THR), 1.0 µM/100 g, with somatostatin (1.0 µM/kg) and ethanol. When given by itself somatostatin significantly reduced mucosal leukotriene generation compared with their generation in saline-treated rats. Sandostatin completely abolished gastric mucosal damage induced by indomethacin administration. In rats treated with somatostatin and indomethacin, this effect was accompanied by reduction of mucosal leukotriene generation. Administration of sandostatin to pylorus-ligated rats significantly reduced gastric acid output. It is suggested that somatostatin may be involved in the pathogenesis of acute ethanol- and NSAID-induced gastric mucosal injury and that part of its protective effect involves interrelationships with the neuropeptides, substance P and VIP, as well as inhibition of mucosal leukotriene production.

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Authors and Affiliations

  1. From the Departments of Medicine and Pathology, Hadassah University Hospital, Hebrew University-Hadassah Medical School, Jerusalem, Israel

    Fanny Karmeli BSc, Rami Eliakim MD, Elimelech Okon MD & Daniel Rachmilewitz MD

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  1. Fanny Karmeli BSc
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  2. Rami Eliakim MD
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  3. Elimelech Okon MD
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  4. Daniel Rachmilewitz MD
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Karmeli, F., Eliakim, R., Okon, E. et al. Somatostatin effectively prevents ethanol-and NSAID-induced gastric mucosal damage in rats. Digest Dis Sci 39, 617–625 (1994). https://doi.org/10.1007/BF02088351

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