Cecectomized Rats Research Articles

Uremic Toxin-Producing Gut Microbiota in Rats with Chronic Kidney Disease

Background: In patients with chronic kidney disease (CKD), many metabolites of gut microbiota retain in the body as uremic toxins (UTs). However, the kinds of bacteria producing UTs are rarely discussed. Methods: We analyzed UT production and the composition of gut microbiota in CKD rats and cecectomized rats. AST-120, a spherical carbon adsorbent, was administrated to evaluate how the precursors of UT affect gut microbiota. Serum and urine levels of UTs were quantified by liquid chromatography/electrospray ionization-tandem mass spectrometry. Gut microbiota were analyzed using 454-pyrosequencing of the 16S rRNA gene. Operational taxonomic unit (OTU) clustering and UniFrac analysis were performed to compare gut microbiota among the groups. Results: Serum and urine levels of indoxyl sulfate and phenyl sulfate were higher in CKD versus control rats (p < 0.05). AST-120 administration decreased UT production (p < 0.01) and changed overall gut microbiota composition in CKD rats. UT urinary excretion and gut microbiota composition changed in cecectomized rats, with the relative abundance of Clostridia- and Bacteroidia-affiliated species being significantly reduced (p < 0.01). We identified candidate indole- and phenol-producing intestinal microbiota, 3 Clostridia, and 2 Bacteroidia. These OTUs have a tryptophanase/tyrosine phenol-lyase gene in the closest sequenced genome out of the OTUs declined following cecectomy. Conclusion: Our data suggest that UT production is correlated with a subset of indigenous gut microbiota. However, UT may be induced by other non-symbiotic microbiota that are influenced by factors other than microbiota populations. The relationship between specific microbiota and UTs in patients requires further clarification.

Dietary mannitol increased the absorption of calcium and magnesium in rats

The effect of mannitol on bone-related mineral absorption and retention and the mechanism was investigated in this study. Fourteen 8-week-old male Wistar rats in experiment 1 and same number and age cecectomized Wistar male rats in experiment 2 were divided into two subgroups of seven animals, respectively, fed diets containing 0 or 4% mannitol for 28days. Mineral balance tests were determined twice during days 8-12 and days 22-26, and the rats were slaughtered on day 28 both in experiment 1 and experiment 2. The whole caecum and colon were collected with the content to analyse tissue weight, content weight, content's pH and moisture, organic acids' concentration and mineral levels. In experiment 1, Ca absorption and retention and Mg absorption were significantly increased by mannitol feeding during days 8-12. Caecal total weight, tissue weight and content weight were increased, the pH of caecum and colon was reduced, and the concentrations of caecal short-chain fatty acids (SCFAs) were modified by mannitol feeding. In experiment 2, during days 8-12 and days 22-26, Ca absorption and retention were significantly lowered by mannitol feeding in cecectomized rats; however, mannitol feeding decreased Mg absorption during days 8-12, but did not impact Mg retention. Colonic total weight, tissue weight and content weight were significantly increased, and colonic pH was reduced by mannitol feeding. In conclusion, dietary mannitol increased the absorption of Ca and Mg and the caecum markedly contributed to this promoting effect of mannitol.

Enhanced trabecular bone resorption and microstructural bone changes in rats after removal of the cecum

The cecum, the proximal part of the large intestine, has the highest rate of calcium absorption compared with other intestinal segments. Previously, we showed that rats with the cecum surgically removed (cecectomized rats) had severe negative calcium balance, low bone mineral density (BMD), and a compensatory increase in colonic calcium absorption. Herein, we used the computer-assisted bone histomorphometric technique and microcomputed tomography (μCT) to analyze bone microstructural defects in cecectomized rats at 1 and 3 mo postsurgery compared with age-matched sham-operated control rats. Relatively low BMD as determined by dual energy X-ray absorptiometry was observed in the femora, tibiae, and lumbar vertebrae of the 3-mo cecectomized rats. μCT analysis revealed decreases in the tibial cortical thickness, periosteal and endosteal perimeters, and moment of inertia in cecectomized rats. The histomorphometric results further showed that trabecular bone volume and number were markedly decreased, whereas trabecular separation was increased in the proximal tibial metaphysis of cecectomized rats, thus leading to a decrease in trabecular volumetric BMD. Since osteoclast surface and eroded surface were increased after cecectomy, such bone loss in cecectomized rats appeared to result from an enhanced bone resorption. Moreover, decreases in bone formation rate and osteoblast surface indicated a suppression of osteoblast-mediated bone formation. In conclusion, cecectomy induced widespread osteopenia in rats presumably by enhancing the osteoclast-mediated bone resorption and suppressing bone formation. The present results underline the important role of cecum in the body calcium homeostasis.

Impaired body calcium metabolism with low bone density and compensatory colonic calcium absorption in cecectomized rats

An earlier study reported that cecal calcium absorption contributes less than 10% of total calcium absorbed by the intestine, although the cecum has the highest calcium transport rate compared with other intestinal segments. Thus, the physiological significance of the cecum pertaining to body calcium metabolism remains elusive. Herein, a 4-wk calcium balance study in cecectomized rats revealed an increase in fecal calcium loss with marked decreases in fractional calcium absorption and urinary calcium excretion only in the early days post-operation, suggesting the presence of a compensatory mechanism to minimize intestinal calcium wasting. Further investigation in cecectomized rats showed that active calcium transport was enhanced in the proximal colon but not in the small intestine, whereas passive calcium transport along the whole intestine was unaltered. Since apical exposure to calcium-sensing receptor (CaSR) agonists similarly increased proximal colonic calcium transport, activation of apical CaSR in colonic epithelial cells could have been involved in this hyperabsorption. Calcium transporter genes, i.e., TRPV6 and calbindin-D(9k), were also upregulated in proximal colonic epithelial cells. Surprisingly, elevated serum parathyroid hormone levels and hyperphosphatemia were evident in cecectomized rats despite normal plasma calcium levels, suggesting that colonic compensation alone might be insufficient to maintain normocalcemia. Thus, massive bone loss occurred in both cortical and trabecular sites, including lumbar vertebrae, femora, and tibiae. The presence of compensatory colonic calcium hyperabsorption with pervasive osteopenia in cecectomized rats therefore corroborates that the cecum is extremely crucial for body calcium homeostasis.

Mannitol Lowers Fat Digestibility and Body Fat Accumulation in Both Normal and Cecectomized Rats

Mannitol is a six-carbon sugar alcohol that is widely distributed in plants. Sugar alcohols are widely used in various food products because of their numerous beneficial health effects. The present study investigated the effects of mannitol consumption on digestion, large gut fermentation and nutrient metabolism in normal and cecectomized male Wistar rats. After 28 d of feeding with three kinds of diet containing 0, 4 or 8% mannitol, mannitol consumption dose-dependently lowered the digestibilities of crude fat and crude protein, the ratio of body fat accumulation to energy absorbed and the hepatic and serum triglyceride levels in normal rats. After 24 d of feeding with three kinds of diet comprising a control diet, a 5% mannitol-containing diet and a 5% fructooligosaccharides (FOS)-containing diet, mannitol lowered the digestibility of fat and the ratio of body fat accumulation to energy consumed and absorbed in cecectomized rats. On the other hand, FOS consumption had no effect on the accumulation of body fat, but lowered the digestibility of fat. FOS consumption greatly improved the accumulation of body ash in cecectomized rats. These results suggest that mannitol has a lowering effect on body fat accumulation, and further indicate that the cecum is not essential for the appearance of effects of mannitol on digestion, absorption and metabolism.

Effects of cecectomy on digestion and retention time of digesta in rats

ABSTRACTThe present experiment aimed to obtain basic knowledge of the role of the cecum in the digestion of protein, fiber and energy, and in the retention of digesta in rats. Twelve healthy male Sprague–Dawley strain rats were used. The experiment lasted for 8 weeks following preliminary feeding. Crude protein [CP], acid detergent fiber [ADF], and energy digestibilities were measured in weeks 1, 4, and 7 of the experiment, while the digesta retention time was measured in weeks 2, 5, and 8. At the end of the test, the colon capacity was measured after killing the rats with diethyl ether. The effects of the cecectomy were not recognized in bodyweight gain, even while the feed intake was high and the feed efficiency was low due to the cecectomy. However these effects were not recognized in the latter half of the test periods. The mean retention time of digesta for the cecectomized rats was about 2 h shorter than that for the control group of rats, while the retention time of digesta in week 8 increased compared to weeks 2 and 5. The digestibility of each substance was significantly lower following the cecectomy. The colon became swollen because of the cecectomy and this swollen colon made up for the capacity of the dissected cecum. It had been considered that the cecum does not play a role in the digestion of nutrition for growth, however, the present results showed two types of effects of cecectomy: one that disappears in accordance with time after surgery (i.e. feed intake and feed efficiency), and another that continues for a longer period (i.e. digestibility, retention time of digesta).

Sorbitol-based osmotic diarrhea: Possible causes and mechanism of prevention investigated in rats

To study the possible causes of sorbitol (S)-based diarrhea and its mechanism of reduction by rice gruel (RG) in cecectomized rats. S was dissolved either in distilled water or in RG (50 g/L) and ingested as a single oral dose (1.2 g/kg body mass, containing 0.5 g/L phenol red as a recovery marker) by S (control) and S + RG groups (n = 7), respectively. This dose is over the laxative dose for humans. Animals were sacrificed exactly 1 h after dose ingestion, without any access to drinking water. The whole gastro-intestinal tract was divided into seven segments and sampled to analyze the S and marker remaining in its contents. Gastric-emptying and intestinal transit were comparatively slower in the S + RG group. Also, the S absorption index in the 3(rd) and last quarter of the small intestine (24.85 +/- 18.88% vs 0.0 +/- 0.0% and 39.09 +/- 32.75% vs 0.0 +/- 0.0%, respectively, P < 0.05) was significantly higher in the S + RG group than in the control group. The S absorption index and the intestinal fluid volume are inversely related to each other. The intestinal mal-absorption of S is the main reason for S-based osmotic diarrhea. Where RG enhanced the absorption of S through passive diffusion, the degree of diarrhea was reduced in cecectomized rats.

Rice Gruel and Rice Starch Reduce Sorbitol-Induced Diarrhoea in Cecectomized Rats

Background/Aims: Sorbitol (S), a widely used sugar substitute in sugar-free products, has shown intolerance manifested by abdominal pain, bloating and diarrhoea in children and adults. The nutritional and S-induced diarrhoea-preventive effect of rice gruel (RG) and rice starch (RS) was studied in cecectomized rats. Methods: During the 41-day experimental period, control, RG or RS, S, and S+RG or RS-containing diets were provided in four consecutive phases. The diet compositions were changed depending on the conditions of the diarrhoea. Faecal appearances of S- and S+RG/RS-fed groups were observed daily and scored (diarrhoea = 2, mixed fae ces = 1, normal faeces = 0) to evaluate the degree of diarrhoea. Results: The diarrhoeal scores were significantly (p < 0.05) decreased in all phases of the RG- or RS-fed group compared to the control group (S). Serum lipid and colonic organic acid concentrations were decreased while faecal bile acids and neutral sterol concentrations were increased in the RG-fed group compared to the control which were measured in the samples collected from the last phase of the experiment. Conclusion: These results indicate that RG and RS may be useful additives in S-containing food products to prevent the possible risk of diarrhoea in humans.

Allergic Airway Eosinophilia Is Suppressed in Ovalbumin-Sensitized Brown Norway Rats Fed Raffinose and α-Linked Galactooligosaccharide

We recently found that dietary raffinose suppressed allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats. Using this model in the present study, we compared the efficacy of other oligosaccharides with that of raffinose. Brown Norway rats were immunized s.c. with ovalbumin on d 0 and exposed to aerosolized ovalbumin on d 20; broncho-alveolar lavage fluid was obtained on d 21. In Expt. 1, rats were fed a control diet or diets supplemented with different oligosaccharides (50 g/kg diet, raffinose, alpha-linked galactooligosaccharide, fructooligosaccharide, and xylooligosaccharide). The number of eosinophils in the fluid was significantly lower in rats fed raffinose and alpha-linked galactooligosaccharide diets than in those fed the control diet. Dietary fructooligosaccharide and xylooligosaccharide did not affect airway eosinophilia. In Expt. 2, i.p. administration of raffinose and alpha-linked galactooligosaccharide, but not fructooligosaccharide and xylooligosaccharide, suppressed airway eosinophilia in rats fed the control diet. In Expt. 3, suppression of airway eosinophilia by dietary alpha-linked galactooligosaccharide occurred in cecectomized rats administered neomycin. Reduced levels of interleukin (IL)-4 and IL-5 mRNA in lung tissue were associated with the suppression of airway eosinophilia. We propose that indigestible oligosaccharides differ in their suppressive effect on allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats and that the effect appears not to be mediated by intestinal microflora.

The Hypocholesterolemic Effect of High Amylose Cornstarch in Rats Is Mediated by an Enlarged Bile Acid Pool and Increased Fecal Bile Acid Excretion, Not by Cecal Fermented Products

Sham-operated and cecectomized rats were fed for 21 d a cholesterol-free purified diet containing (200 g/kg) either normal cornstarch (CS) or high amylose cornstarch (HACS). In both types of rats, those fed the HACS diet had a significantly lower plasma total cholesterol concentration and a significantly larger intestinal bile acid pool than those fed the CS diet. In cecectomized rats, those fed the HACS diet had significantly lower plasma HDL and LDL cholesterol concentrations, a significantly greater fecal bile acid excretion and a significantly lower hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase mRNA concentration than those fed the CS diet. The plasma triglyceride concentration and LDL-receptor mRNA concentration were not affected by the diet or cecectomy. In sham-operated rats, the propionate concentration in the cecal contents was significantly greater in those fed the HACS diet than in those fed the CS diet. Compared with sham-operated rats, cecectomized rats had significantly enhanced cholesterol 7alpha-hydroxylase activity. In intact rats, biliary bile acid flux into the small intestine was significantly greater in those fed the HACS diet than in those fed the CS diet. Thus, the hypocholesterolemic effect of HACS appears to be mediated by accelerated fecal excretion of bile acids and increases in the intestinal pool and biliary flux of bile acids, and not by cecal fermentation products.

Molecular Mechanism of the Effect of Fructooligosaccharides on Calcium Absorption

Previous reports have demonstrated through the use of animal models that dietary fructooligosaccharides (FOS) exert stimulatory effects on the absorption of the minerals; calcium, magnesium, and iron. Recently, these effects were also clinically confirmed in humans. This paper reviews studies that used the techniques of molecular biology to elucidate the mechanisms by which FOS stimulates calcium absorption for which the small intestine has long been considered a primary site. However, Ohta et al. reported that the large intestine, and the cecum in particular, has an important role. This conclusion was based on the observation that the stimulatory effect of FOS on calcium absorption was not observed in cecectomized rats. The contribution of paracellular and transcellular paths was suggested for the stimulation caused by FOS. Transcellular transport is a multistep process comprising several components and is under the regulation of vitamin D. One component is calbindin-D9k (CaBP), a calcium binding protein. The upstream region of the CaBP gene was analyzed, and a responsive sequence for vitamin D receptor was identified. Mucosal cells were then obtained from FOS-fed rats, and the expression of CaBP protein and mRNA were determined. Dietary FOS decreased the expression of CaBP in the small intestine, but resulted in increased levels in the cecum and colorectum. Since protein and mRNA both demonstrated similar patterns of expression, the effects of FOS can be seen to affect CaBP at the transcription level. Furthermore, the changes in CaBP expression were proportional to both the level of apparent calcium absorption and the amount of FOS ingested. This means that the increase of calcium absorption induced by FOS comprises paracellular and CaBP-mediated transcellular transport. In a hypothetical model, short-chain organic acids produced from FOS by fermentation were proposed as key elements to regulate both the paracellular and the transcellular transport of calcium. However, the molecular mechanisms of this regulation have not yet been clarified.

Effect of rice bran on intraintestinal fermentation and cholesterol metabolism in cecectomized rats

The effects of rice bran on intraintestinal fermentation and cholesterol metabolism in cecectomized rats were investigated. Male F344 rats, allocated into three groups: cecectomized rats fed rice bran containing 76.3 g water-soluble fiber/kg and 183 g oil/kg (CERB), sham-operated rats fed rice bran (SHRB) and standard rats fed cellulose with 0.5% cholesterol and 0.125% sodium cholate for 1 week. The body weight in the SHRB group was significantly higher than that in the CERB group and the food intake in the SHRB group was significantly lower than in the cellulose group for 1 week. There were no significant differences in the liver weight among groups. The fecal excretion in the CERB group was significantly higher than that in the cellulose group. The fecal pH in the SHRB group was the lowest among the groups. The serum total cholesterol, very low density lipoprotein + intermediate density lipoprotein + low density lipoprotein-cholesterol, high density lipoprotein (HDL)-cholesterol, triacylglycerol concentrations, and the liver cholesterol concentrations in the CERB and SHRB groups were significantly lower than that in the cellulose group, and the total cholesterol, HDL-cholesterol and liver cholesterol concentrations in the SHRB group were the lowest among the groups. There were no significant differences in the fecal neutral sterol and total bile acid extraction among the groups. The fecal propionic acid, butyric acid and total short-chain fatty acid concentrations in the SHRB group were significantly higher than those in the other groups. Escherichia coli ( E. coli) in the fecal microflora was the main bacterium in the CERB and cellulose groups. On the other hand, Lactobacillus in the fecal microflora was the main bacterium in the SHRB group. The results of this study demonstrate that the rice bran was fermented in the cecum and that the metabolites such as propionic acid and butyric acid, and rice bran oil may be effective in lowering cholesterol levels in the presence of excess cholesterol in the diet.

A mixture of organisms affects cholesterol metabolism together with rat cecal flora.

The effects of a mixture of organisms on cecal fermentation and cholesterol metabolism in sham-operated and cecectomized rats were investigated. Male F344 rats, allocated into four groups: cecectomized rats fed a mixture of organisms (CEMO), cecectomized rats fed rice bran (CERB), sham-operated rats fed a mixture of organisms (SHMO), and sham-operated rats fed rice bran (SHRB) for 4 weeks. The diets had 0.5% cholesterol and 0.125% sodium cholate added. There were no significant differences in the body weight gain and food intake among the groups. The cecal pH in the SHMO group was significantly lower than that in the other groups. The total cholesterol and (VLDL + IDL + LDL)-cholesterol concentrations in serum were significantly lower in the SHMO group than that in the SHRB group, and the triacylglycerol concentration in the sham-operated rats tended to decrease compared to the cecectomized rats. The fecal cholesterol excretion in the CERB group was higher than that in the other groups, and that in the SHMO group was significantly higher than in the SHRB group. The acetic acid, propionic acid, n-butyric acid, and total short-chain fatty acid concentrations in the cecum contents were significantly higher in the SHMO group than those in the other groups. Streptococcus, Bifidobacterium, and Lactobacillus in the SHMO group tended to be higher than the other groups and Bacteroidaceae in the CEMO and CERB groups were significantly higher than that in the SHMO group. The results demonstrate that the mixture of organisms was fermented with the cecal contents and that the metabolites such as short-chain fatty acid lowered the serum total cholesterol and liver cholesterol concentrations in the rats fed a cholesterol-containing diet.

Effect of guar gum on glucose metabolism in cecectomized rats

We hypothesized that short chain fatty acid (SCFA) fermented in the cecum of rats fed a guar gum diet is responsible for the hypoglycemic effect. Thus, to evaluate the role of SCFA in glucose metabolim, rats with or without cecum were fed a guar gum-containing diet for 4 weeks, and parameters including blood glucose and SCFA in portal blood were determined. The level of insulin-responsive glucose transporter (GLUT4) was also measured to evaluate the effect of SCFA on glucose metabolism at the cellular level. Blood glucose levels in both cecectomized and normal rats that were fed a cellulose-based diet significantly, decreased after their diet was changed to one containing guar gum at the level of 5% ( w w ). However, no subsequent difference was found between the two groups. When an oral sucrose load was performed after 3 weeks, untreated and cecectomized rats responded similarly. After feeding a guar gum diet for 4 weeks, the rats were killed, and blood from the portal vein and aorta was taken to measure SCFA and plasma biochemical parameters. Cecectomy did not have any influence on glucose, lipids, and insulin levels in the blood. Portal plasma acetic and propionic acids in ceoectomized rats dramatically decreased by one-half and one-tenth those of the control rats, respectively. There was no difference in the amount and translocation rate of GLUT4 isolated from adipose tissues between the two groups when the animals were killed after 4 weeks. From these results, it is suggested that, at least in normal rats, SCFA fermented in the digestive tract, if any, is not a primary cause of glucose-lowering action by guar gum. Physicochemical characteristics of guar gum in the upper intestine (e.g., gel-forming capacity) may be important in determining blood glucose level.

Expression of apolipoprotein A-I mRNA in liver and intestine of cecectomized rats fed beet fiber

Sham-operated and cecectomized rats were fed a cholesterol-free diet with no added fiber (fiber-free) for 10 days, followed by the diet of 15% beet fiber for 10 days. The plasma cholesterol concentrations in rats fed the fiber-free diet were not significantly different between sham-operated and cecectomized groups. Plasma cholesterol concentrations in sham-operated rats were decreased by feeding the beet fiber diet, whereas those in cecectomized rats did not change. Final plasma total cholesterol concentrations in cecectomized rats were significantly higher than in sham-operated rats. This difference was due mainly to lower HDL cholesterol concentrations. The cecectomized rats also tended to have higher apolipoprotein A-I concentrations in plasma. Northern blot analysis revealed that the relative concentrations of ileal apolipoprotein A-I mRNA were the same in the two groups, while hepatic apolipoprotein A-I mRNA levels were significantly higher in cecectomized rats than in sham-operated rats. These data demonstrate that the cecectomy abolished the hepatic apolipoprotein A-I mRNA-lowering effect of dietary beet fiber, and it is suggested that the cecum plays an important role in the regulation of hepatic apolipoprotein A-I expression which seems to be responsible for the hypocholesterolemic effect of dietary beet fiber.

The cecum does not participate in the stimulation of intestinal calcium absorption by calcitriol.

Intestinal Ca absorption from the diet consumed during one night was measured in male rats fed a normal (0.5%) Ca, low fiber (3% cellulose) diet by determining the decrease in 47Ca/47Sc ratio between diet and feces. One-half of the rats had been cecectomized 9 weeks previously at 14 weeks of age. Calcitriol injections, given intraperitoneally the morning of the experiment, stimulated fractional intestinal Ca absorption 2.5-fold in intact rats (16.9 +/- 2.0% to 42.2 +/- 1.8%) and 2.3-fold in cecectomized rats (20.1 +/- 1.4% to 46.8 +/- 1.2%). Similar results were obtained when the data were calculated in terms of total Ca absorption expressed as mg/day. Thus, although the cecum can absorb Ca when diets contain large amounts of digestible fiber, cecectomy does not influence the stimulation of intestinal Ca absorption induced by calcitriol in vitamin D-replete rats fed a low fiber diet.

Ileorectostomy or Cecectomy but Not Colectomy Abolishes the Plasma Cholesterol-Lowering Effect of Dietary Beet Fiber in Rats

Adult male rats were fed a cholesterol-free diet with no added fiber (fiber-free) or with 10% cellulose or beet fiber. After 7 d of feeding, plasma total cholesterol concentrations were significantly lower in rats fed beet fiber than in those fed fiber-free or cellulose diets. This difference was due mainly to lower HDL cholesterol concentrations and remained significant for 28 d. The hypocholesterolemic effect of beet fiber relative to fiber-free disappeared when the cecum and colon were concurrently resected (ileorectostomy). Plasma cholesterol concentrations were the same in colectomized rats as in sham-operated rats fed the same diet and significantly lower in animals fed the beet fiber diet than in those fed the fiber-free diet. In cecectomized rats fed beet fiber, plasma cholesterol concentrations were intermediate between sham-operated rats fed the beet fiber diet and cecectomized or sham-operated rats fed the fiber-free diet. Fecal bile acid excretion was higher in rats fed the beet fiber diet than in those fed the fiber-free diet but did not correlate with plasma total cholesterol concentration. In rats with intact ceca, cecal total and individual short-chain fatty acids correlated negatively with plasma total cholesterol concentration. Dietary beet fiber lowers plasma cholesterol concentrations in rats, and the lower digestive tract, especially the cecum, seems to be necessary for this effect.

P-66 - 16,16-Dimethyl prostaglandin E2 (dmPGE2)-induced secretory diarrhea in cecectomized rats and evaluation of antidiarrheal agents.

P-66 - 16,16-Dimethyl prostaglandin E2 (dmPGE2)-induced secretory diarrhea in cecectomized rats and evaluation of antidiarrheal agents.

Cecectomized rat: A model of experimental secretory diarrhea in conscious animals

Evaluation of antisecretory antidiarrheal agents in animal models is limited primarily to extrapolations of efficacy from enteropooling studies in vivo, isolated intestinal loops in situ, and Ussing flux chamber preparations in vitro. While these standard techniques are useful, they do not mimic secretory diarrhea. Our studies indicate that in rats, the cecum may serve a “reservoir” function in response to secretagogue administration. Thus, diarrhea is not observed consistently and reliably in this species to allow valid evaluation of potential antidiarrheal agents. Therefore, we have developed a reproducible model of secretory diarrhea utilizing conscious cecectomized rats by surgical resection of the cecum, without compromising ileocecal patency, and by the use of potent intestinal secretagogues. Animals quickly recover and maintain normal growth and other physiologic parameters for as long as 60 days. After 48 hr on standard chow, secretory diarrhea can be induced by oral administration of standard intestinal secretagogues (dimethyl prostaglandin E 2, cholera toxin, or carbachol). Dimethyl prostaglandin E 2 (300 μg/kg, p.o.) induces diarrhea within 1 hr that continues for approximately 3.5 hr. Oral administration of known antidiarrheal agents chlorpromazine (10 mg/kg), clonidine (1 mg/kg), or morphine (10 mg/kg) all significantly reduce fecal output within 30–60 min following administration. These studies indicate that in the rat, the cecum may serve as a fluid reservoir during periods of small intestinal hypersecretion and that the cecectomized rat serves as a useful, accurate, and reliable tool for evaluating new compounds with proposed antidiarrheal activity

Effect of cecectomy on feeding and defecation in rats.

The effect of cecectomy on food intake and defecation was studied in Wistar rats fed ad libitum or under restriction. Food intake, fecal output, dry matter and water content of feces, and numbers of scybala increased significantly in both groups of cecectomized rats. The weight of scybala and their dry matter and water content also increased after cecectomy. Water intake did not change significantly. It was considered that changes in the parameters after cecectomy may have resulted from lowered digestion and enhancement of propulsive activity in the gastrointestinal tract.