The Syrian hamster: a reproducible model for studying changes in intestinal fluid secretion in response to enterotoxin challenge

Abstract

Syrian hamsters respond in a predictable and reproducible manner to intragastric administration of purified cholera enterotoxin by intraluminal accumulation of fluid in the small bowel, cecum, and proximal colon. In the majority of animals this process is self limiting, and recovery occurs with full reabsorption of intestinal fluid by 30 to 35 h. The secretory response to 75 gg of cholera toxin has been defined, and the model was utilized to study the inhibitory effects of indomethacin, polymyxin B sulfate, glucose electrolyte solutions, and colchicine. These studies demonstrate its potential usefulness as a convenient and inexpensive technique for evaluation inhibit intestinal fluid secretion. of pharmacological agents that might Several animal species have been shown to be susceptible to infection with Vibrio cholerae or in response to exposure to its enterotoxin, including dogs (18), cats (9), rabbits (15), rats (19), chinchillas (3), guinea pigs (14), mice (6), and hamsters (2). A live animal model that can be used to study response to the pure enterotoxin in a reproducible manner may have importance for studies of enterotoxin-induced intestinal fluid secretion, diarrheal disorders, changes in intestinal microbiological flora, and the immune response (4).In this study, experiments were performed that characterize the reproducible response of the Syrian hamster to cholera enterotoxin (CT) and demonstrate its usefulness as an inexpensive and convenient technique to study pharmacological agents that may inhibit intestinal fluid secretion. MATERIALS AND METHODSPurified CT was purchased from Schwarz/Mann, Orangeburg, N.Y. (lot A2-2301). When reconstituted in 1.0 ml of water, 5 mg of protein was suspended in 0.05 M Tris-0.001 M disodium ethylenediaminetetraacetate-0.003 M NaN3-0.2 M NaCl at pH 7.5. The toxin was diluted in phosphate-buffered saline (PBS) (pH 7.3) containing 0.1% bovine serum albumin. Syrian hamsters (90 to 110 g) were purchased from Charles River Lakeview Hamster Colony, Newfield, N.J., and maintained in cages with free access to food and water.Batches of six animals were used and challenged by administration intragastrically of 1.5 ml of toxin or PBS via an infant feeding tube (Resiflex 5 Fr. feeding tube; Cutter Lab. Inc., Berkeley, Calif.). Doses of 5, 10, 25, 50, 75, 100 and 200 ,g of toxin were used. Animal comportment was observed in respect to their general appearance, activity, feeding, and drinking habits. Animals were sacrificed by decapitation at 3, 6, 12, 24, and 36 h after intragastric challenge; blood was collected for hematocrit determination at that time and determined with microhematocrit tubes. The abdomen was opened, and the bowel was carefully ligated at the pylorus-ileo-cecal junction and ceco-colic junction and midcolon with double ties. The macroscopic appearance of the bowel was noted. Several methods were utilized to measure and document fluid accumulation. Since the total volume of fluid was small, it proved easier and more accurate to express fluid accumulation by weight ...

Effect of indomethacin on intestinal water transport in salmonella-infected rhesus monkeys

“…We have previously reported that indomethacin pretreatment of rabbits can inhibit intestinal secretion induced by infection with Shigella flexneri or Vibrio cholerae or secretion induced by cholera toxin (7,9). The ability of indomethacin or aspirin to reduce cholera-mediated secretion in various animal species has also been reported by several other groups (2,3,11,15,21). Thus, it seems that nonsteroidal anti-inflammatory agents have the ability to enhance intestinal water transport in the normal intestine as well as the intestine secreting in response to a variety of stimuli.…”