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PubMed1989

Effects of rioprostil on bicarbonate secretion by guinea-pig gastric mucosa in vitro.

Spontaneous and prostaglandin-stimulated HCO3 secretions are studied in guinea-pig isolated gastric mucosa by means of pH-stat techniques. Antral mucosa exhibits a spontaneous HCO3- secretion of about 0.5 mumol/cm2h that is almost abolished by serosal addition of indomethacin (10(-5) mol/l). Fundic HCO3- secretion of the same magnitude is revealed upon suppression of acid secretion by serosal omeprazole (10(-5) mol/l). It is stimulated by serosal or mucosal addition of either PGE1, the synthetic primary alcohol analogue of PGE1, rioprostil, or dimethyl-PGE2. Effective concentrations range from 10(-4) to 10(-6) mol/l. Short-circuit current remains unchanged, arguing against involvement of electrogenic mechanisms of HCO3- secretion. Tissue conductance increases in the presence of all compounds tested, but only during luminal exposure to rioprostil does this increase go beyond that observed in time controls. Thus, enhanced HCO3- secretion seems to be due to cellular mechanisms rather than to a rise in passive (paracellular) HCO3- flow.

16,16-Dimethylprostaglandin E2↗
PubMed1988

Intestinal transport of thiamin and thiamin monophosphate in rat everted jejunal sacs: a comparative study using some potential inhibitors.

Rat everted jejunal sacs were incubated for 15 and 30 min at 37 degrees C in oxygenated Krebs-Henseleit buffer, pH 7.4, containing 0.2 microM [3H]-thiamin (3H-T) or [3H]-thiamin monophosphate (3H-TMP) with and without 10 mM 1-phenylalanine (PAL) or 2.5 mM levamisole (LEV). The concentrations of 3H-T and its phosphoesters in sac wall and serosal fluid were determined by a radiometric method after electrophoretic separation. In separate experiments, thiamin pyrophosphokinase (TPKase) and thiamin pyrophosphatase (TPPase) activities were determined in mucosal scrapings, with and without PAL or LEV, by using a radiometric and a colorimetric method, respectively. 3H-TMP was transported partly unchanged by an active mechanism similarly to 3H-T, but less efficiently. During transport, 3H-TMP was also enzymatically transformed to thiamin (T) and thiamin pyrophosphate, which accumulated in the tissue. In the serosal fluid, the concentration of 3H-TMP exceeded that of 3H-T. Presence of PAL or LEV with 3H-T or 3H-TMP in the incubation medium reduced the serosal transport and the tissue content of T compounds. LEV caused a dose-dependent inhibition of TPKase without affecting TPPase, whereas PAL inhibited both activities to about the same extent. These results indicate that the transport of TMP involves a number of different processes similar to those responsible for T transport. The effects of PAL and LEV underline the importance of phosphorylation-dephosphorylation coupling.

Animals↗
PubMed1983

Selective fixation with glutaraldehyde of ADH-induced urea permeability sites in toad bladder.

Toad bladders exposed to vasopressin (ADH) and then fixed on the mucosal surface with 1% glutaraldehyde were highly permeable to water and to urea compared to control bladders fixed in the absence of hormone. When identical conditions of fixation were were used, but the concentration of glutaraldehyde was decreased to 0.25%, the ADH-induced increase in membrane permeability to urea was preserved whereas water permeability was not. About 74% of the hormone-induced urea permeability sites were preserved by glutaraldehyde and were stable to changes in temperature as suggested by a constant value for the activation energy of urea movement of 5.4 kcal/mole (4-33 degrees C). In other studies bladders were exposed at low temperatures to 0.17% glutaraldehyde applied either to the serosal or the mucosal surface. The ADH-induced increase in membrane permeability to urea, bulk water, and tritiated water was well preserved with serosal fixation, but not with mucosal fixation. The observation that the urea pathway can be selectively preserved with 0.25% glutaraldehyde applied to the mucosa indicates that this structure is more accessible and (or) more sensitive to low-dose glutaraldehyde than is the ADH-induced water pathway. The observation that glutaraldehyde is more effective in stabilizing the ADH-induced urea channels from the serosal than from the mucosal surface indicates that these channels are not fixed at the extracellular surface of the apical plasma membrane. It appears, rather, that glutaraldehyde exerts its effects from an intracellular position, where it cross-links components of the urea channels at the cytoplasmic surface of the apical membrane and (or) inactivates the intracellular machinery responsible for the removal or dispersal of the ADH-induced urea permeability sites.

Aldehydes↗
PubMed2004

Expression of heparanase gene, CD44v6, MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas.

AIM: To explore the expression of heparanase gene, CD44v6, MMP-7 and nm23 proteins in human gastric carcinoma as well as their relationship with the clinicopathological factors. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expressions of heparanase mRNA in 43 human gastric carcinomas and 10 adjacent normal gastric tissues. Streptavidin-peroxidase (S-P) two step method was used to measure the immunohistochemical expression of CD44v6, MMP-7 and nm23 protein in 43 human gastric carcinomas. RESULTS: The expression of heparanase gene was positive in 29 cases of gastric cancer with a positive rate of 67.4%, which was significantly higher than those in adjacent normal gastric tissues (P<0.05). The heparanase mRNA expression was significantly related to advanced stage of disease, serosal infiltration, lymph node metastasis and size of tumors (P<0.05), but not related to tumor location, gross and histological types of the cancer, peritoneal dissemination and liver metastasis (P>0.05). The positive rate of CD44v6, nm23 and MMP-7 proteins was 76.7%, 37.2% and 60.5%, respectively. The CD44v6 protein expression was significantly related to serosal infiltration, lymph node metastasis and TNM stage of disease (P<0.05). The nm23 protein expression was significantly related to the tumor gross appearance, lymph node and peritoneal metastasis (P<0.05). The MMP-7 protein expression was significantly related to serosal infiltration and TNM stage of disease (P<0.05). In an attempt to measure the association between these agents, we found that the expression of heparanase mRNA had significantly negative correlation with the expression of CD44v6 and MMP-7 protein (P<0.05), the expression of MMP-7 protein had significantly positive correlation with the expression of CD44v6 protein (r=0.568, P<0.05), the expression of MMP-7 protein had no correlation with the expression of nm23 protein (P>0.05), and the expression of nm23 protein had no correlation with the expression of CD44v6 protein (P>0.05). CONCLUSION: Despite their different mechanisms of action, heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas. Instead of metastatic spreading, MMP-7 may be just related to the invasion of gastric carcinomas. However, co-detection of these factors may be important to predict metastatic spreading in such patients.

Adult↗
PubMed1999

Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma.

BACKGROUND: The majority of advanced gastric carcinoma patients with serosal invasion die of peritoneal recurrence, even when a curative gastrectomy is performed, because peritoneal recurrence occurs due to intraperitoneal free tumor cells that detach from the serosal-invaded focus. In an attempt to prevent peritoneal recurrence, intraperitoneal hyperthermic chemoperfusion (IHCP) treatment was combined with aggressive surgery. METHODS: Between March 1987 and December 1996, 141 gastric carcinoma patients with macroscopic serosal invasion were allocated randomly to 2 groups. Seventy-one patients underwent IHCP combined with surgery (IHCP group) and the remaining 70 patients underwent surgery alone (control group). IHCP was performed just after gastric resection and alimentary tract reconstruction under general anesthesia along with systemic hyperthermia. RESULTS: Postoperative complications were reported in 2 of the 71 patients in the IHCP group and in 2 of the 70 patients in the control group. The peritoneal recurrence rate in the IHCP group was significantly decreased (P = 0.0000847) compared with that in the control group. The 2-year, 4-year, and 8-year survival rates for the IHCP group were 88%, 76%, and 62%, respectively, whereas those for the control group were 77%, 58%, and 49%, respectively. The IHCP group thus reaped a significant survival benefit (P = 0.0362) compared with the control group. CONCLUSIONS: Although this study was conducted randomly for a small number of patients, compared with the control group, the IHCP group had a high survival rate and better prognosis.

Carcinoma↗
PubMed2000

Extensive metabolism of diltiazem and P-glycoprotein-mediated efflux of desacetyl-diltiazem (M1) by rat jejunum in vitro.

The objective of this in vitro study was to investigate both the intestinal metabolism and transport of diltiazem (DTZ) and its major metabolites in rat jejunum. Metabolism experiments were performed with everted sacs, whereas sheets mounted in a symmetrical twin chamber system were used in transport studies. DTZ was rapidly desacetylated by the rat jejunum to the principle metabolite desacetyl-diltiazem (M1). In addition, minor amounts of N-demethyl-diltiazem and desacetyl-N-demethyl-diltiazem were formed. Due to the rapid desacetylation, it proved difficult to study the transport of DTZ in this model. However, the primary metabolite M1 was shown to be subjected to P-glycoprotein (Pgp)-mediated efflux. The flux rate of M1 was 6- to 7-fold higher from the serosal to the luminal compartment than in the opposite direction. Both coadministration of verapamil and Pgp monoclonal antibody dose dependently increased luminal-to-serosal flux and decreased serosal-to-luminal flux. In conclusion, rat jejunum metabolizes DTZ extensively in vitro, and the major primary metabolite M1 is subjected to Pgp-mediated efflux.

ATP Binding Cassette Transporter, Subfamily B↗
PubMedDate not supplied

Everted rat intestinal sacs: a new model for the quantitation of P-glycoprotein mediated-efflux of anticancer agents.

P-Glycoprotein (p-gp) situated in the epithelium of the gastrointestinal tract is a recognised barrier limiting oral absorption of antitumour agents. Here we describe the rat everted gut sac as a new in vitro model for quantitation of p-gp-mediated efflux of anti-cancer agents using [3H]vinblastine, [14C] doxorubicin and verapamil as reference compounds. Tissue and serosal uptake of [3H]vinblastine was linear over 90 min (0.031 +/- 0.001 and 0.003 +/- 0.001 ng/mg protein/h respectively). [14C]Doxorubicin tissue accumulation was significantly lower; 0.006 +/- 0.001 ng/mg protein/h (p < 0.05) whereas serosal transfer was significantly higher 0.017 +/- 0.001 ng/mg protein/h (p < 0.05) than [3H]vinblastine. Addition of verapamil (40 ng/mL) increased significantly both tissue accumulation of [3H] vinblastine and [14C]doxorubicin (to 0.060 +/- 0.024 and 0.034 +/- 0.012 ng/mg protein/h respectively) and serosal transfer (to 0.006 +/- 0.002 and 0.023 +/- 0.001 ng/mg protein/h) (p < 0.05 in all cases). The reproducibility of this in vitro model suggests that the rat everted gut sac is a useful screening tool for studying transport of p-gp substrates and potential p-gp modifiers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Stimulation by nitric oxide of HCO3- secretion in bullfrog duodenum in vitro--roles of cyclooxygenase-1 and prostaglandins.

The effect of nitric oxide (NO) on HCO3- secretion was examined in vitro using the isolated preparation of bullfrog duodenum, in relation to cyclooxygenase (COX) isozymes and endogenous prostaglandins (PGs). The tissue was bathed in unbuffered Ringer solution gassed with 100% O2 on the mucosal side and HCO3- Ringer's solution gassed with 95% O2-5% CO2 on the serosal side. The HCO3- secretion was measured by a pH-stat method using 10 mM HCl as the titrant to keep the mucosal pH at 7.4. NOR-3 [(+/-)-(E)-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamine] was used as a NO donor and added to the serosal solution. To analyze the NOR-3 action, the effects of dibutyryl guanosine-3', 5'-cyclic monophosphate (dbcGMP), methylene blue, indomethacin (nonselective COX-inhibitor) and NS-398 (selective COX-2 inhibitor) on the HCO3- response were also examined. NOR-3 (1 x 10(-4) and 3 x 10(-4) M) caused an increase of HCO3- secretion in a dose-dependent manner, reaching the level of 2.5 times greater than basal values at 2 hr later. Likewise, dbcGMP (1 x 10(-3) M) also caused a significant increase of the duodenal HCO3- secretion. The HCO3- stimulatory action of NOR-3 was significantly attenuated by methylene blue (5 x 10(-5) M) and indomethacin (1 x 10(-5) M) but not by NS-398 (1 x 10(-5) M), and indomethacin also suppressed the HCO3- response to dbcGMP. The serosal release of PGE2 was significantly increased by both NOR-3 and dbcGMP, and these responses were inhibited by indomethacin but not NS-398. These results suggest that NO increases HCO3- secretion in Bullfrog duodenum in vitro, and this action is dependent on cGMP-related COX-1 activation and mediated by PGs.

16,16-Dimethylprostaglandin E2↗
PubMed2001

Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa in vitro.

We examined the effect of NO on acid secretion in vitro using isolated preparations of Bullfrog stomach. The bullfrog fundic mucosa was bathed in unbuffered Ringer solution gassed with 100% O2 on the mucosal side and HCO3- Ringer's solution gassed with 95% O2/5% CO2 on the serosal side, and the acid secretion was measured at pH 5.0 using the pH-stat method and by adding 5 mM NaOH. Serosal addition of a NO donor NOR-3 (10(-5) approximately 10(-3) M: (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexnamine) caused an increase of acid secretion in a dose-dependent manner, the effect lasting about 1 hr and reaching a maximal level of 2-fold the basal values. The acid stimulatory effect of NOR-3 was mimicked by another NO donor SNAP (10(-3) mol/L: S-nitroso-O-N-acetyl-penicillamine) and markedly and markedly inhibited by prior administration of cimetidine (10(-5) mol/L) as well as compound 48/80 (the mast cell degranulator). Likewise, the increased acid response to NOR-3 was significantly mitigatd by pretreatment with carboxy-PTIO (a NO scavenger) or superoxide dismutase (SOD), but not by indomethacin or methylene blue (a guanylyl cyclase inhibitor). Neoither L-NAME, L-arginine nor dibutyryl guanosine-3',5'-cyclic monophosphate (dbcGMP) has any effect on the basal acid secretion. Serosal addition of NOR-3 caused a significant increase in the luminal release of histamine, and this response was inhibited by pretreatment with either compound 48/80, carboxy-PTIO or SOD. These results suggest that the NO donor increases gastric acid secretion in the isolated frog stomach in vitro, and this action is mediated by endogenous histamine released from mast cells, the process being cGMP-independent but requiring the presence of superoxide radicals. In addition, it was speculated that the histamine releasing action of NO may be due to peroxynitrite produced by NO and superoxide radicals.

Animals↗
PubMed2000

[Judgement of gross type and local invasion of advanced gastric carcinoma by spiral computed tomography].

OBJECTIVE: To evaluate the value of spiral computed tomography(sCT) in the judgement of gross type, invasion to serosa and adjacent organs of advanced gastric carcinoma. METHODS: The sCT results of 53 cases of advanced gastric carcinoma undergone gastrectomy were compared with surgical pathologic findings. RESULTS: The accuracy of judging gross type, location and size of gastric carcinoma was 92.5%, 88.7%, 81.1% respectively; 80.5% of serosal invasion was correctly judged by extraluminal fat sign, while 63.4% by serosal contour sign (P < 0.05). Different serosal types could be differentiated by CT features. The accuracy of judging invasion to pancreas, spleen and transverse colon was 87.8%, 87.8%, and 90.2%; and the specificity was 96.7%, 97.0% and 96.7%, respectively. CONCLUSION: Spiral computed tomography is of help in the identification of the gross type, invasion to serosa and adjacent organs of gastric cancer in its stage of progression.

Adult↗
PubMed2002

Phenol red inhibits uptake of phosphate by the everted gut sacs of mice.

Uptake of phosphate by the everted intestinal sacs of mice was measured at various concentrations of this anion in the incubation medium. Phenol red when added to the serosal side was able to inhibit the uptake of phosphate significantly, while uptake of glucose or proline was unaffected. When para amino hippuric acid was present along with phenol red in the serosal compartment, the inhibition exerted by the dye on phosphate uptake was significantly less. These findings suggest that entry of phenol red into gut tissue from the serosal side interferes with the mucosal uptake of phosphate by the everted intestinal sacs of mice.

Absorption↗
PubMed1975

[Water balance in the european eel (Anguilla anguilla L.). Role of the oesophagus in the utilisation of drinking water and a study of the osmotic permeability of the gills (author's transl)].

10 New experimental devices are described which allow chonic measurements of drinking rate and osmotic gill permeability in the eel. 20 The oesophagus of the seawater (SW) silver eel plays a role in osmoregulation. It decreases the concentration of Cl- and Na+ of the ingested SW without losing water in the serosal to mucosal direction. This allows for immediate water absorption in the intestine and decreases the quantity of ions actively absorbed by the intestine. In the freshwater (FW) silver eel, the oesophagus is impermeable to water, Cl- and Na+. The ionic impermeability exists only in the serosal to mucosal direction. A mucosal to serosal permeability to Cl- and Na+ exists in the FW oesophagus receiving hypertonic drinking water, this promotes seawater adaptation. 30 The osmotic gill permeability, measured in vivo in the silver eel, is very low in FW and decreases slightly in SW. Thus, the silver eel has an osmotic gill permeability preadapted to SW life. The kinetics of FW to SW adaptation are described.

Adaptation, Physiological↗
PubMed2003

[Peritoneal lavage cytology in 66 patients with gastric carcinoma].

OBJECTIVE: To evaluate the clinical and prognostic value of peritoneal lavage cytology (PLC) in detecting free cancer cells (FCC). METHODS: PLC of 66 gastric cancer patients being operated was prospectively analyzed to assess the prognostic significance of positive cytological finding and its relation with serosal invasion, lymph node metastasis and stage classification. RESULTS: The overall positive rate of cytology was 36.4% (24/66). These was a closely relation between positive cytology results and serosal invasion (P = 0.025), abdominal lymph node involvement (P < 0.005) and stage classification. Peritoneal recurrence in patients with positive cytological findings was significantly higher than that with negative results (P = 0.006 7). CONCLUSION: Micrometastasis to the abdominal cavity, formed by free cancer cells exfoliated from the tumor, are significantly responsible for peritoneal dissemination. Serosal invasion and metastatic nodes have greater risk for positive cytology and implies poor prognosis. Peritoneal lavage cytology, if practiced in all gastric cancer patients being operated, can predict the operative effect and prognosis, increase the accuracy of clinical stage and provide information for further adjuvant therapy.

Adult↗
PubMed1992

Metabolism of absorbed glucose in mouse jejunum: influence of arachidonic acid, non-steroidal anti-inflammatory drugs and eicosanoids.

The involvement of arachidonic acid and eicosanoids in glucose absorption and metabolism was investigated in isolated mouse jejunum. Characteristics of glucose absorption and its metabolic fate are reported. Reduction in the dietary precursor of arachidonic acid, linoleic acid, and inhibition of phospholipid hydrolysis with mepacrine reduced glucose absorption with no effect on metabolism, although mepacrine increased the proportion of luminal to serosal lactate release. Bradykinin and n-FMLP enhanced metabolism by 2.1- and 2.4-fold, respectively, both reducing the percentage of metabolised glucose converted to lactate, while neither influenced absorption. Both indomethacin and NDGA decreased absorption and enhanced metabolism. The percentage of metabolised glucose converted to lactate decreased and the ratio of luminal to serosal lactate release was unchanged. In the absence of inhibitors, PGE2 (5 microM) decreased absorption by 28%, metabolism by 24% and total lactate production by 32% and LTB4 (20 nM) increased only absorption by 32%. PGE2 release into the perfusates was predominantly serosal (1-10 nM) and was inhibited by indomethacin. PGE2 could not reverse the indomethacin-induced decrease in absorption, but reversed the enhancement of metabolism by 89% and total lactate production by 60%. In conclusion, while the specificity of the drug-related absorptive effects remain unclear, alterations in the utilisation of the absorbed glucose via drug-induced changes in arachidonic acid synthesis and metabolism are apparent. Furthermore, exogenous PGE2 may protect against the effects of indomethacin and itself reduces active glucose absorption, the metabolism of the absorbed glucose and the amount of lactate formed.

Animals↗
PubMed1992

Endogenous intestinal metallothionein possibly contributes to the renal accumulation of cadmium.

At low levels of dietary cadmium chloride, cadmium accumulates directly in the kidneys and not in the liver. As dietary cadmium induces intestinal metallothionein (MT), intestinal CdMT complexes could be at least partly responsible for the renal accumulation of oral cadmium. For this to be possible, however, serosal release of mucosal CdMT would be required. To test this hypothesis, we perfused isolated rat small intestinal segments (Fisher-Parsons method) in an attempt to demonstrate the release of intestinal MT. After two weeks of feeding dietary cadmium chloride, intestinal MT was induced in amounts proportional to the dietary cadmium level. Subsequent in vitro perfusion of the small intestine revealed a concentration-dependent release of intestinal MT on the serosal side. When 109CdCl2 was present in the perfusion medium, 109Cd appeared on the serosal side mainly in the MT fraction. These results indicate that endogenous intestinal MT may deliver CdMT to the organism, thus possibly contributing to the renal accumulation of orally ingested cadmium.

Animals↗
PubMedDate not supplied

Gastrectomy for advanced gastric carcinoma with invasion to the serosa.

A review of gastrectomy for 332 patients who had advanced gastric cancer with serosal exposed (S2) or adjacent organs invaded (S3) was made. Simple gastrectomy (SG) was carried out in 144 patients while radical gastrectomy (RG), which consisted of systemic lymphadenectomy in addition to SG, was used for the other 188 patients. The type of gastrectomy was chosen arbitrarily by the surgeons except that SG was usually selected when some non-curable factors were present. The operative mortality of SG was 2.7% and that of RG was 3.2%. More lymphnodes could be obtained by RG. Of the 152 patients with S2 who received RG, 46.7% of metastatic lymphnodes could not be identified by SG, while of the 36 patients with S3, 75% of metastatic nodes would be misjudged if SG was carried out. The 5-year-survival rate of RG for stage 3 patients was 42.4% and that for stage 4 patients was 28.2%. Better postoperative long-term-survival was achieved by RG than SG in both stage 3 and 4 patients. When considering the curability of the gastrectomy, the best outcome in stage 3 patients was found in those who underwent an absolute curative resection. Of the stage 4 patients those who received an absolute non-curative resection had the worst result. We recommend that RG be the procedure of choice in treatment of serosal gastric cancer in the absence of non-curable factors. Other adjuvant therapies may be considered after an absolute non-curative gastrectomy in stage 4 serosal cancer patients when multiple non-curable factors were present.

Adult↗
PubMed1992

[Intracellular pH of surface epithelial cells and the movement of bicarbonate ions under acid-base imbalance in gastric mucosa].

To investigate the effect of the acid-base imbalance on the gastric mucosal defense mechanism, the intracellular pH of gastric surface epithelial cells were measured with double-barreled H+ selective microelectrodes in the isolated antral mucosa of bullfrog stomach. By knowing the intracellular pH and the PCO2 of the serosal perfusate, the intracellular HCO3- concentration was estimated, and the rate of HCO3- secretion was directly measured with the pH-stat method in mounted preparations on a Ussing's chamber. Both the calculated intracellular HCO3- concentration and the rate of HCO3- secretion were dependent on the exogenous HCO3- supplied from the serosal perfusate. The alkaline tide raised the intracellular HCO3- concentration, thus increasing the mucosal buffering power against acid. Under mild respiratory acidosis, the production of endogenous HCO3- from the serosal CO2 was enhanced, and both the intracellular HCO3- concentration and the rate of HCO3- secretion were increased. As a result, the intracellular pH was maintained at a physiologically optimal level, and the ability of gastric mucosal protection was strengthened by enrichment of cellular bicarbonate supply. It is confirmed in this study that the maintenance of acid-base status in the cell is indispensable in the protection of gastric mucosa against acid invasion.

Acid-Base Imbalance↗
PubMed1992

[In vitro studies of intestinal absorption and biotransformation of furazolidone].

The intestinal biotransformation and absorption of the nitrofuran furazolidone were investigated in isolated gut cells and in the isolated perfused gut. In case of inhibiting furazolidone metabolism by high oxygen tension almost equal concentrations of the parent compound were measured on the mucosal and serosal side of the perfused gut segments. Lowering oxygen supply in order to adjust it to physiological conditions caused a complete degradation of furazolidone in isolated gut cells. Accordingly, hardly any unchanged furazolidone was detected on the serosal side of the isolated perfused gut. An open-chain cyanometabolite was formed in both systems indicating a reductive metabolic process which induces highly reactive intermediates. This metabolite also reached the serosal side of the gut representing the systemic circuit. Thus, the low systemic bioavailability is due to the considerable intestinal metabolism rather than a limited absorption. Unknown metabolites will reach the systemic circuit, the toxic potential of which is still obscure. Independent of its metabolic degradation, thus probably due to its redox cycle furazolidone inhibited intestinal functions as e. g. the flow of water and the transport of sodium.

Animals↗