NUTRIENT ESSENTIAL FATTY ACIDS & GASTRIC MUCOSAL INJURY

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We propose to investigate the role of nutrient essential fatty acids (EFA)-namely arachidonic and linoleic in the prevention and healing of gastric mucosal injury in the rat produced by ethanol, aspirin and taurocholic acid. We will determine whether: 1) acute and/or chronic administration of EFA may a) prevent or reduce gastric mucosal damage or b) speed up healing of pre-existing injury; 2) diet deficient in EFA predisposes to gastric mucosal injury, increases its extent or delays healing, and the mechanism(s) responsible for these effects. The rationale for these studies is that EFA are natural DIETARY precursors of prostaglandins which have been shown to protect the gastric mucosa against acute injury produced by damaging factors and to accelerate healing of gastroduodenal ulcers in man. Studies will be performed on male Sprague Dawley rats receiving: (1) single dose of EFA as a pretreatment or as a posttreatment of mucosal injury, (2) diet deficient in EFA for 10 weeks, (3) diet rich in EFA for 10 weeks, (4) diet sufficient in EFA (controls). Gastric mucosal injury will be produced by acute intragastric administration of absolute ethanol, acidified aspirin or taurocholic acid. Gastric mucosal damage, its healing and mucosal protection will be assessed: A) macroscopically by scoring and computerized image analysis B) histologically with morphometric quantitation of necrosis C) by determination of mucosal cell proliferation kinetics D) ultrastructurally with scanning and transmission electromicroscopy E) functionally by measurements of ionic fluxes, potential difference and intragastric pH, and F) biochemically by measurements of luminal loss of DNA, protein and blood and the concentration or prostaglandins in the gastric contents. TO EXPLORE THE MECHANISM(S) OF EFA PROMOTED GASTRIC MUCOSAL PROTECTION WE PLAN TO STUDY: (1) THE EFFECT OF DNA AND PROTEIN SYNTHESIS INHIBITORS AND OF MICROTUBULES AND MICROFILAMENTS DISRUPTIVE AGENTS ON EFA PROTECTION; (2) RESISTANCE OF RESTORED SURFACE EPITHELIUM TO SUBSEQUENT INJURY; (3) ACTION OF EFA ON ISOLATED GASTRIC MUCOSAL CELLS (SURFACE, PROLIFERATIVE ZONE) THEIR VIABILITY AND ABILITY TO GENERATE PROSTAGLANDINS. Our long term objective is an assessment of the value (and application) of nutrient EFA in prevention and healing of gastroduodenal mucosal injury in man.