Rat Rectum Research Articles

Low-dose glucocorticoids maintain Na-H exchange in distal colon of adrenalectomized rats.

With in vivo perfusion we demonstrated that physiological doses of glucocorticoids restore Na and Cl absorption in adrenalectomized rat colon. The absorption is spironolactone and amiloride resistant and is inhibited by the Na-H inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), suggesting that glucocorticoids modulate Na-H antiport. The present in vitro study examines pathways mediated by glucocorticoids in adrenalectomized rat distal colon and rectum. In vivo administration of 2.5 micrograms/100 g body wt dexamethasone did not alter serosal-to-mucosal flux or tissue electrical parameters but restored mucosal-to-serosal flux and net Na and Cl absorption within 2-3 h of administration to levels found in intact rat colon. Transport was not inhibited by 10(-5) M amiloride but was eliminated by 10(-5) M EIPA. After 26 h of dexamethasone, an amiloride-resistant short-circuit current was stimulated, accompanied by increased residual ion flux in rectum, but not distal colon, suggesting that a delayed or secondary effect of glucocorticoids is stimulation of electrogenic anion secretion. Thus adrenalectomy reduces net ion flux in distal colon by its effect on electroneutral mucosal-to-serosal NaCl flux. Small doses of glucocorticoids completely ameliorate this effect via stimulation of the Na-H antiport. Glucocorticoids maintain basal electroneutral NaCl absorption in distal rat colon.

Development of a shielded 241Am applicator for continuous low dose rate irradiation of rat rectum by low energy photons

Development of a shielded 241Am applicator for continuous low dose rate irradiation of rat rectum by low energy photons

Enhancement Effect of Lauric Acid on the Rectal Absorption of Propranolol from Suppository in Rats.

In a previous paper, we have demonstrated that medium chain fatty acids significantly enhance the in vitro rectal absorption of propranolol (PL) and that the enhancement may be partly due to the formation of a complex with a fatty acid at a 1:1 molar ratio. To confirm in vivo the enhancement effect of lauric acid on PL absorption, PL suppositories with lauric acid at various molar ratios were administered to rat rectum. PL absorption from Witepsol and macrogol suppositories with lauric acid at a 1:1 molar ratio was much larger than that after PL alone and the 1:2 or 1:3 molar ratio ones. The bioavailability (BA) after administration of the 1:1 molar ratio suppository (PL, 4 mg/kg) was 1.6- and 2.1-fold for the Witepsol and macrogol formulations respectively, compared with that after PL alone. A similar result was obtained with the PL solid dispersion suppository with lauric acid at a 1:1 molar ratio, showing a 1.7-fold higher BA compared with PL alone. The release of PL from the macrogol suppository was significantly faster at a 1:1 molar ratio than that of other preparations, but not so in the solid dispersion suppository. There was not good agreement between the release rates of PL from the suppositories and the plasma levels after dosing. These results supported the concept that a portion of PL, by forming a 1:1 complex with lauric acid, would penetrate across the rectal mucosa more easily than PL alone.

Rectal electrogenic secretion‐‐is it a putative indicator of intestinal secretory status induced by nutritional deprivation in the rat?

Intestinal secretion is enhanced by starvation in rats. The rectum from fed and 3-day-starved rats generates a basal electrogenic ion transfer (short-circuit current) in vitro which is mainly electrogenic Na+ absorption (amiloride-sensitive, 66-71%) with a small component of electrogenic chloride secretion (furosemide-sensitive, 14-22%). Bethanechol, a muscarinic agonist, caused an increase in the short-circuit current (mainly furosemide-sensitive chloride secretion) and potential difference in rectums from both fed and starved rats but the respective values for the starved animals were 100% and 64% greater. In starvation, the rat rectum is an indicator of intestinal secretory status. The result warrants investigation of human rectal electrogenic secretion in nutritional deprivation.

Effect of cyclodextrins on biological membrane. I. Effect of cyclodextrins on the absorption of a non-absorbable drug from rat small intestine and rectum.

The effects of three kinds of cyclodextrins (CyDs), alpha-, beta- and gamma-CyD on biological membranes were investigated by changes in absorption of a non-absorbable drug, sulfanilic acid (SA), from the rat small intestine and rectum using an in situ perfusion technique. The absorption of SA from the intestine was slight and was not affected by the addition of CyDs. After pretreatment with a mucolytic agent, N-acetyl-L-cysteine (N-Ac), the absorption of SA was increased compared with SA alone in the presence of only beta-CyD. Similar treatment with sodium deoxycholate (SDC) and sodium lauryl sulfate (SLS) to gastro-intestinal membrane showed the enhanced absorption of SA by the addition of beta-CyD. The mucin layer on the surface of the gastro-intestinal membrane may play an important role in the absorption of drugs. On the other hand, enhanced absorption of SA from the rat rectum was not induced by beta-CyD with or without pretreatment with N-Ac, SDC or SLS. Simultaneously, the release of neutral sugars in the perfusate after treatment with adjuvants was also observed with N-Ac, SDC and SLS. These results indicate that the mucin layer works as a barrier to the increased absorption of SA by beta-CyD.

Determination of a Suitable Dosage of Lysine-Vasopressin and Triglycyl-Lysine-Vasopressin, Given in a Gel-Solution Locally in the Rectum of Rats for Possible Radioprotective Purposes

In order to develop a method for selective radioprotection of the rectal mucosa, a dose-response study was carried out using triglycyl-lysine-vasopressin and lysine-vasopressin. The vasopressin was dissolved in a gel-solution of either Blanose (sodium-carboxymethyl-cellulose), Klucel (hydroxypropyl-cellulose) or Natrosol (hydroxyethyl-cellulose). The solution had a higher viscosity than water thus enabling rectal administration of the drug without any operative measures. The maximum vasopressin dose that can be given without causing any significant changes in systemic circulation was determined for the different solutions and vasopressins. For triglycyl-lysine-vasopressin this dose was 1,600 micrograms when it was dissolved in Blanose and 128 micrograms when dissolved in Natrosol. Lysine-vasopressin could be given in a maximum dose of 16 micrograms dissolved in Natrosol. Klucel solution did not seem suitable for this purpose. For further investigations, 16 micrograms lysine-vasopressin dissolved in Natrosol seems to be the most promising combination.

An immunohistochemical study of somatostatin-containing nerves in the aganglionic colon of human and rat.

The distribution of somatostatin-like immunoreactive (SOM-LI) nerves was elucidated immunohistochemically in the gut tissues from patients with Hirschsprung's disease and congenital aganglionosis rats. In the normoganglionic human colon, SOM-LI nerve cell bodies were found to a greater extent in the submucous plexus and to a lesser extent in the myenteric plexus. However, they were rarely observed in both the plexuses of the oligoganglionic segment. SOM-LI nerve fibres were widely distributed in the aganglionic bowel. The circular muscle layer of the distal aganglionic segment was densely innervated by SOM-LI nerve fibres which are probably derived from the extrinsic, hypertrophic nerve bundles. A decreased number of the intramuscular nerves fibres were seen in the proximal aganglionic segment. In the colon and rectum from adult and 21-day-old rats, SOM-LI cell bodies were numerous in both plexuses. On the other hand, enteric neurons were completely lacking from the colon and rectum of congenital aganglionosis rats of 21 days old. No neuronal elements staining for SOM were disclosed in these aganglionic segments of mutant rats. A possible origin and pathophysiological role of the extrinsic nerve fibres containing SOM in the diseased bowel are discussed. It is concluded that SOM-LI nerves in the human distal colon comprise both intrinsic and extrinsic elements, while SOM nerves in the rat colon and rectum are of only intrinsic origin.

Rectal absorption enhancement of des-enkephalin-gamma-endorphin (DE gamma E) by medium-chain glycerides and EDTA in conscious rats.

The stability of the neuroleptic peptide des-enkephalin-gamma-endorphin (DE gamma E; Org 5878) in the rectal lumen and the rectal bioavailability of DE gamma E were investigated in conscious rats. Furthermore, the influence of peptidase inhibition, peptidase saturation, and absorption enhancement on DE gamma E bioavailability were evaluated. Na2EDTA (0.25%, w/v) prolonged the degradation half-life of DE gamma E in the ligated colon from 33 +/- 7 to 93 +/- 45 min. Without adjuvant, tritium-labeled DE gamma E was absorbed from the rat rectum to a very low extent (0-4%). After administration of an excess of unlabeled DE gamma E or with Na2EDTA, comparable results were obtained. The medium-chain glyceride preparation MGK markedly enhanced the rectal DE gamma E bioavailability, up to 8-20%, which was further increased to 10-44% by coadministration of Na2EDTA. No substantial influence of varying the rectal delivery rate was observed. The results suggest that absorption enhancement and enzyme inhibition both are essential for effective increase of rectal peptide bioavailability.

Radiation tolerance of the rat rectum to fractionated X-rays and pi-mesons

A 2.5 cm segment of the rectum of female F344 rats was irradiated with up to 10 fractions of X-rays or pions. Transient signs of acute proctitis were followed by chronic rectal injury starting at about 2 months. Rectovaginal fistulas were frequently observed in animals with severe chronic injury. Two patterns of chronic injury were observed, an early type consisting of deep ulcers and fistulas, and a late type characterized by vascular injury, fibrosis and muscosal cysts. In a 4-fraction X-ray experiment, the influence of a low-residue diet was compared with a regular diet, showing no significant differences in pathology or survival. Isoeffective doses were determined for the occurrence of severe rectal injury at 250 days. Fitting the data to an LQ-model yielded an α β ratio of 13 Gy for pions, and 6.5 Gy for X-rays. Increasing the overall treatment time from 9 days to one month gave a significant rise in isoeffective doses for chronic injury. This suggests that the more delayed types of injury did not develop independently from the acute mucosal changes. The RBE of pions for rectal injury at 250 days was 1.2 for single doses, increasing to about 1.4–1.5 at a dose per fraction of 4 Gy. These values are similar to those obtained in other acute and late responding tissues.

Immunohistochemical identification of supportive cell types in the enteric nervous system of the rat colon and rectum.

The non-neuronal, supportive cells of the enteric nerve plexus were investigated in the colon and rectum of adult and developing rats by means of immunohistochemistry, utilizing antisera against GFA protein and S-100 protein. Immunoreactivity to GFA protein was almost exclusively found in cells associated with the myenteric plexus and a small number of cells within the submucous ganglia. On the other hand, the use of S-100 protein antiserum resulted in the visualization of all supportive elements in the enteric nervous system. However, two types of supportive cells could be tentatively differentiated in the enteric nerve plexus during the second week of postnatal development, using GFA protein and S-100 protein antisera; GFA protein-positive cells were clearly discernible from S-100 protein-positive cells in terms of both the morphological profiles and immunohistochemical properties. It was assumed that at least two different types of supportive cells are contained in the enteric nerve plexus. We suggest that in the enteric nervous system the terms "glial cells" and "Schwann cells" should be employed to designate the supportive cells containing GFA and S-100 proteins, and cells containing S-100 protein, respectively. We discuss the possibility that glial cells are associated with the parasympathetic preganglionic fibres directly derived from the central nervous system, while Schwann cells originate from the neural crest.

The effects of chronic ethanol administration on polyamine content during dimethylhydrazine-induced colorectal carcinogenesis in the rat.

Chronic ethanol (EtOH) consumption has been implicated as a co-carcinogen, selectively promoting rectal tumor formation. We studied the effects of EtOH consumption on tumor formation and polyamine content (putrescine, spermidine and spermine) in proximal and distal colon and rectum of Sprague-Dawley rats treated with the procarcinogen 1,2-dimethylhydrazine (DMH). Sixty-four adult male rats were pair fed nutritionally complete liquid diets with 36% of calories supplied as EtOH or isocaloric carbohydrates. Both groups received 4 weeks of the liquid diet followed by 4 weeks of standard laboratory chow during which 50% of the rats in each group received DMH (30 mg/kg) or vehicle s.c. weekly. This cycle was repeated four times (32 weeks). Animals were sacrificed at the end of each 8 week cycle and normal appearing and available tumor bearing tissue from proximal and distal colon and rectum was obtained for polyamine content and histology. Five animals, unexposed to DMH or EtOH served as baseline controls. There were no consistent regional differences in putrescine, spermidine or spermine of baseline controls. A progressive decrease in tissue putrescine was seen in all three regions of the control group and was significant at 24 and 32 weeks versus baseline controls. In all three regions, chronic EtOH consumption prevented the decrease in tissue putrescine. Spermidine content was also significantly increased in the distal colon of EtOH-treated animals compared to baseline values. Consistent changes in spermine content were seen in any treatment group or region. A significant increase in putrescine content of normal appearing and tumor-bearing tissue of DMH treated animals at 32 weeks was noted. Chronic EtOH administration did not augment rectal or colonic polyamine content in DMH-treated animals. Likewise, chronic EtOH consumption did not alter the number, size or distribution of large bowel tumors of DMH treated animals.

Net ion fluxes and zero flux limiting concentrations in rat upper colon and rectum during anaesthesia-induced aldosterone liberation

Thiobutabarbital anaesthetized and abdominally operated control rats develop high endogenous plasma levels of both aldosterone and corticosterone during the course of a 12 h experiment. This effect was used as a model for examining 'acute' steroid action (i) on net ion and water fluxes and (ii) on zero flux luminal limiting concentrations in rat upper colon (proximal 50% of large intestine) and rectum (distal 40%). Experiments of both kinds consisted of 8 independent 90 min measuring periods. (i) In rectum net fluxes of Na, K, osmolytes (sum of all solutes) and water started at low levels around zero, began to rise about 2 h after plasma levels of aldosterone had increased, and reached plateau values around the 6th hour of anaesthesia. In upper colon, fluxes of Na, K, Cl, and osmolytes were high from the beginning and did not vary significantly with time. (ii) At zero flux conditions limiting concentrations of Na in the hormonally unstimulated phase of the experiment were 20 +/- 3 mM in upper colon and 22 +/- 3 mM in rectum. After maximal endogenous aldosterone liberation zero flux concentrations were 5.2 mM in upper colon and 2.2 mM in rectum, corresponding to luminal fluid to plasma ratios (LF/P) of 0.040 and 0.016, respectively. Amiloride reduced the maximal Na gradient in rectum to a LF/P of 0.3 but was not effective in upper colon and did not prevent the stimulating effect of aldosterone in this segment. Under all experimental conditions zero flow concentrations of K were higher than consistent with a solely passive distribution, indicating simultaneous passive and active secretion in both segments. In contrast to the findings of others, the luminal fluid remained isoosmolar with plasma in all zero flux experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible mechanisms for the enhancement of rectal absorption of hydrophilic drugs and polypeptides by aqueous polyacrylic acid gel.

The mechanisms of absorption enhancing effect by polyacrylic acid gel were investigated in rats. Polyacrylic acid gel significantly enhanced rectal absorption of phenol red, a hydrophilic compound. The enhanced absorption was concentration dependent in the range of 0.01-0.05% w/v polyacrylic acid in gel. The gel also significantly increased the influx and the net influx on water movement in rat rectum. Further, the histological change in rectal epithelium after administration of the polyacrylic acid gel was examined with transmission electron microscopy. The structural changes, which were removal of the mucus and fenestrations of the intercellular spaces 5 and 10 min after administration of polyacrylic acid gel, were observed. These changes were reversible and returned relatively soon to normal levels. Thus, the absorption promoting effect by polyacrylic acid gel may occur mainly with increased water influx as a driving force.

Glycyrrhizic acid and its hydrolysate as mineralocorticoid agonist

Mineralocorticoid activity of glycyrrhetinic acid (GR) was studied in vivo (electrical potential difference in rat rectum) and in vitro (brush border Mg 2+-HCO − 3 ATPase in rat small intestine, kidney cytosol binding of GR with and without RU-28362, anti-glucocorticoid compound) in order to clarify the mechanism of mineralocorticoid-like activity of GR. Scatchard analysis of [ 3H]aldosterone showed that K d of higher affinity site (type I) 6.0 × 10 −9 M, B max 1.0 × 10 −14 mol/mg protein, and K d of lower affinity site (type II) 1.6 × 10 −7M, B max 7.5 × 10 −14 mol/mg protein. GR competed for [ 3H]aldosterone binding sites in kidney cytosol at the concentration of 10 4 times as that of unlabeled aldosterone. RU-28362 displaced aldosterone binding curve, whereas GR binding kinetic was not affected by this compound. Adrenalectomy caused a significant fall in brush border Mg 2+-HCO − 3 ATPase activity (75% reduction compared with the initial level) which was not restored by GR administration. Electrical potential differences in the adrenalecomized rats were significantly lower than those in the control rats, which did not increase after GR administration.

Effect of nonsteroidal anti-inflammatory drugs on the absorption of macromolecular drugs in rat rectum.

Effect of nonsteroidal anti-inflammatory drugs on the absorption of macromolecular drugs in rat rectum.

Application of photoacoustic microscopy to analysis of biological components in tissue sections.

Photoacoustic microscopy was applied ot the determination of dye (alcian blue 8GS) spotted on a mucin layer. The determination range in a 40 μm diameter area was 40-1200 pg. The total dye quantity in the spot (ca. 2mm diameter) was determined by integrating the quantities in the 40 μm diameter area within 15% error, irrespective of the uniformity of the distribution. This method was applied to the analysis of acidic mucopoly-saccharide in the rat rectum and in rat eyeball sections stained with alcian blue 8GS. The dye quantity was estimated to be 40-640 pg in the microregion of 40 μm diameter area and 1.5-1.8 μg in the whole region in ca. 8 μm thick sections. These quantities corresponded to 1.6-26 ng and 60-72 μg of mucin, respectively, based on the weight binding ratio of 40 of mucin to the dye in solution.

Enhancement of Absorption of Sodium Cromoglycate Across the Normal and Regenerating Rat Rectum

Enhancement of Absorption of Sodium Cromoglycate Across the Normal and Regenerating Rat Rectum

Chronic Effects of Neutrons and Charged Particles on Spinal Cord, Lung, and Rectum

The effects of multifraction irradiation with X rays, neutrons, and pions on the rat cervical and lumbar spinal cord, mouse lung, and rat rectum have been investigated. The linear-quadratic model was used to analyze the effectiveness per unit dose for various tissue responses. It is concluded that the dependence of tolerance doses on fraction size is considerably reduced for both intermediate (pions) and high-LET (neutrons) radiations, as shown by the observed alpha/beta ratios in the range of 20-50. With accurately defined alpha/beta values for various tissues and types of radiation, the same tolerance formalisms can be used as proposed for low-LET radiation. The effectiveness of pion irradiation shows a significant dependence on dose rate when treatment times are long and repair of subeffective damage occurs during the irradiations. For late effects in spinal cord, lung, and rectum, RBE values of pions are 1.5 or less at doses per fraction in the range of 1.2-4.5 Gy.

Muscarinic receptor agonist-antagonist interaction in the rat rectum: are there ways of activating the same receptors?

The interaction between the muscarinic receptor agonists, carbachol, acetylcholine (ACh) and methacholine, and antagonists, atropine, gallamine, 4-DAMP and pirenzepine, was studied on the rat isolated rectum preparation. ACh (1.93 X 10(-8)-1.95 X 10(-6) M), methacholine (8.7 X 10(-8)-1.1 X 10(-6) M) and carbachol (1.1 X 10(-7)-3.5 X 10(-6) M) induced contractions that were reversibly antagonized by atropine (1.9 X 10(-9)-4.8 X 10(-8) M), 4-DAMP (1.5 X 10(-8)-2.86 X 10(-7) M) gallamine (1.12 X 10(-6)-1.12 X 10(-4) M) and pirenzepine (2.8 X 10(-7)-7.0 X 10(-6) M). The pA2 values were atropine: 8.99 +/- 0.28, 9.29 +/- 0.14 and 8.86 +/- 0.05; 4-DAMP: 8.39 +/- 0.10, 8.66 +/- 0.15 and 8.26 +/- 0.30, gallamine: 5.85 +/- 0.23, 5.73 +/- 0.25 and 5.96 +/- 0.10 and pirenzepine: 6.85 +/- 0.44, 7.17 +/- 0.13 and 7.21 +/- 0.03 against ACh, methacholine and carbachol, respectively. The experimental dose-ratio (atropine + gallamine) was greater than the expected dose-ratio (as predicted by the Paton & Rang rule) for ACh and methacholine while the experimental dose-ratio closely approximates the expected dose-ratio for carbachol. It is suggested that atropine, 4-DAMP pirenzepine and gallamine act on the same receptors but gallamine allosterically altered the binding of the agonists and antagonists to varying extents.

A comparison of prednisolone absorption and the effect of sodium salicylate and mannitol in normal and damaged rat bowel

A model of ulcerated bowel was produced in the rat rectum by treatment with Brij 35 suppositories. Prednisolone absorption from enemas in normal and damaged bowel was assessed using an in situ rectal loop. In animals 20 h after damage drug absorption was reduced but returned to normal levels after one week. Co-administration of equiosmolar sodium salicylate (1 and 2% w/v) and mannitol (2.5 and 4.1% w/v) solutions in normal bowel induced a significant water flux into the lumen and changed the plasma tritium profile compared to the control. In damaged bowel plasma tritium levels remained low following co-administration of mannitol (2.5% w/v) but were restored to normal control levels by co-administration of salicylate (1% w/v). The altered absorption in normal bowel can be attributed in part to osmotic stress but in damaged bowel the difference between the effect of equiosmotic solutions of salicylate and mannitol suggests that a different mechanism is operating.