COLON MUCOSAL CELL-DAMAGE BY AMMONIA IN RATS

Colons of male Sprague-Dawley rats were perfused, in situ, with ammonium (NH4+) or sodium (Na+) and acetate (CH3COO-) or chloride (Cl-) to determine the effects of the cations and anions or their interactions on the colon mucosa. Solutions simulating ileal fluid were delivered at 0.4 mL/min at 38-degrees-C via cannulae inserted at the cecal-colonic junction. Effluents were collected by cannulae inserted in the anus. In the first experiment, perfusion with the control solution or with the control solution having 35 mmol/L NaCl replaced by equimolar amounts of ammonium acetate, ammonium chloride or sodium acetate showed that only ammonium-containing solutions caused histological damage, loss of mucus, and significant losses of carbohydrate and DNA (P < 0.05). The losses of carbohydrate and DNA expressed in mu-g . cm-1 . 30 min-1 were as follows: control, 13.4 and 1.0; ammonium acetate, 31.8 and 1.6; sodium acetate, 16.0 and 0.6; ammonium chloride, 24.1 and 1.3, respectively. In the second experiment, perfusion with control fluid containing 35 or 70 mmol/L ammonium acetate at pH 6.8, 7.4 or 8.0 increased carbohydrate and DNA losses into the effluents compared with the pretest period (P < 0.05), without significant effects related to influent pH. These studies are consistent with the concept that the life span of colon cells is shortened by concentrations of ammonia found in the colon under normal conditions and that ammonia enhances cell proliferation in the colon mucosa.