The Action of Inhalation Anesthetics on the Gastrointestinal Tract

Bennet, Donald R.; Bass, Paul

doi:10.1007/978-3-642-65055-0_13

“…However, it can be assumed that the complexes in this solution will pass intact via the stomach into the intestinal lumen, since the gastric secretion of hydrogen ions is decreased under Mebumal narcosis (38,39). However, it can be assumed that the complexes in this solution will pass intact via the stomach into the intestinal lumen, since the gastric secretion of hydrogen ions is decreased under Mebumal narcosis (38,39).…”

Section: Discussionmentioning

confidence: 99%

Effects of Chelating Agents on Oral Uptake and Renal Deposition and Excretion of Cadmium

Engström¹

1984

Environmental Health Perspectives

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The gastrointestinal absorption, transport, tissue deposition and excretion of cadmium was studied in adult male mice given a single oral LD50 dose of 109Cd-labeled CdCl2 alone or in combination with nitrilotriacetic acid (NTA), sodium tripolyphosphate (STPP) or ethylenediaminetetraacetic acid (EDTA). Blood, intestinal mucosa, liver and kidneys were analyzed for 109Cd at different times after exposure and the influence of the chelating agents on Cd binding to metallothionein and other tissue ligands was also studied. Acute toxicity was noted. Complex formation between Cd and EDTA was studied in solutions containing Cd:EDTA at 1:04 and 1:4 molar ratios. Adult male mice were exposed orally or by direct infusion into the stomach to either of the two solutions (containing an LD50 dose of Cd). Body retention and tissue deposition of Cd was recorded after 4 (direct infusion) or 21 days (oral exposure), and the mortality in different exposure groups observed. Adult male were also exposed to a low oral dose of 109Cd-labeled cadmium (0.5 mg/kg), followed by 18 months continuous administration of NTA, (500 ppm) STPP (500 ppm) or EDTA (50 ppm) in the drinking water or the chelating agent in combination with Cd (50 ppm), Cd alone (50 ppm) or deionized water. Whole-body retention of 109Cd, tissue deposition of 109Cd and total Cd and development of proteinuria were observed. When cadmium was given with an excess of EDTA, all Cd ions were bound in a 1:1 Cd-EDTA complex. Decreased acute toxicity was observed which was related to increased body elimination of cadmium. The Cd passes though the body still bound to EDTA and is excreted via the kidneys in this form. Similar results were found in mice exposed to Cd + NTA, while gavage of CD + STPP led to an initially decreased systemic uptake of Cd and thereafter to a prolongation of the biological half-time and thus a comparatively higher body retention of the metal. Cd may form a 2:1 complex with EDTA in the presence of excess cadmium. An increased retention and toxicity of cadmium was seen after direct infusion of this solution, while gavage resulted in a decreased toxicity. The effect of different chelating agents on acute cadmium toxicity and metabolism seemed to be due to changes in the stability of the administered chelate complexes, due to variation in pH and to the availability of metal binding ligands such as metallothionein in vivo. NTA, STPP and EDTA had no effect on the metabolism or toxicity of cadmium after long-term low dose oral exposure.

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“…The reason for an increased retention and toxicity of cadmium following direct infusion of Cd + EDTA (1:0.4) is not fully understood. However, it can be assumed that the complexes in this solution will pass intact via the stomach into the intestinal lumen, since the gastric secretion of hydrogen ions is decreased under Mebumal narcosis (38,39). Fewer hydrogen ions are thus available to compete with cadmium for the binding to EDTA.…”

Section: Discussionmentioning

confidence: 99%

Effects of chelating agents on oral uptake and renal deposition and excretion of cadmium

Engström¹

1984

Environ Health Perspect

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The gastrointestinal absorption, transport, tissue deposition and excretion of cadmium was studied in adult male mice given a single oral LD50 dose of 109Cd-labeled CdCl2 alone or in combination with nitrilotriacetic acid (NTA), sodium tripolyphosphate (STPP) or ethylenediaminetetraacetic acid (EDTA). Blood, intestinal mucosa, liver and kidneys were analyzed for 109Cd at different times after exposure and the influence of the chelating agents on Cd binding to metallothionein and other tissue ligands was also studied. Acute toxicity was noted. Complex formation between Cd and EDTA was studied in solutions containing Cd:EDTA at 1:04 and 1:4 molar ratios. Adult male mice were exposed orally or by direct infusion into the stomach to either of the two solutions (containing an LD50 dose of Cd). Body retention and tissue deposition of Cd was recorded after 4 (direct infusion) or 21 days (oral exposure), and the mortality in different exposure groups observed. Adult male were also exposed to a low oral dose of 109Cd-labeled cadmium (0.5 mg/kg), followed by 18 months continuous administration of NTA, (500 ppm) STPP (500 ppm) or EDTA (50 ppm) in the drinking water or the chelating agent in combination with Cd (50 ppm), Cd alone (50 ppm) or deionized water. Whole-body retention of 109Cd, tissue deposition of 109Cd and total Cd and development of proteinuria were observed. When cadmium was given with an excess of EDTA, all Cd ions were bound in a 1:1 Cd-EDTA complex. Decreased acute toxicity was observed which was related to increased body elimination of cadmium. The Cd passes though the body still bound to EDTA and is excreted via the kidneys in this form. Similar results were found in mice exposed to Cd + NTA, while gavage of CD + STPP led to an initially decreased systemic uptake of Cd and thereafter to a prolongation of the biological half-time and thus a comparatively higher body retention of the metal. Cd may form a 2:1 complex with EDTA in the presence of excess cadmium. An increased retention and toxicity of cadmium was seen after direct infusion of this solution, while gavage resulted in a decreased toxicity. The effect of different chelating agents on acute cadmium toxicity and metabolism seemed to be due to changes in the stability of the administered chelate complexes, due to variation in pH and to the availability of metal binding ligands such as metallothionein in vivo. NTA, STPP and EDTA had no effect on the metabolism or toxicity of cadmium after long-term low dose oral exposure.

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“…It is known that the gastric secretion of hydrogen ions and the propulsion motility in the gastrointestinal tract is decreased under mebumal anaesthesia (Benett &Bass 1972;Goodman & Gilman 1975). Thus, the decreased formation of HCI under narcosis will probably result in a raise of the pH i n the stomach region which in turn may be one explanation for the presence of intact Cdz-EDTA complexes under such conditions.…”

Section: Ph -7mentioning

confidence: 99%

Influence of Different Cd‐EDTA Complexes on Distribution and Toxicity of Cadmium in Mice after Oral or Parenteral Administration

Engström

¹

,

Norin

²

,

Jawaid

³

et al. 1980

Acta Pharmacologica et Toxicologica

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The distribution and toxicity of cadmium in mice was investigated after single exposure to CdCl2 (labelled with 109Cd) alone or in combination with EDTA (ethylenediaminetetraacetic acid) in Cd: EDTA molar ratios of 1:0.4 or 1:4, respectively, by different routes of exposure: I. Subcutaneous injection. The mortality rate observed (during a period of three weeks) in the groups of mice exposed to either Cd alone (3.2 mg=0.028 mmol Cd/kg b.wt.)or Cd in combination with EDTA was 60% and 0%, respectively. Furthermore a marked decrease of the whole‐body activity of 109Cd was seen during the first 24 hours following exposure to Cd and EDTA (about 80% in the Cd + EDTA 1:4‐group and about 45% in the 1:0.4‐group, compared to only about 4% in the Cd‐group). Cd given alone or simultaneously with an excess of EDTA was bound similarly to different proteins in liver and kidneys, 5 hours after exposure (i.e. mainly bound to low molecular weight proteins) whereas relatively more of the Cd administered in the Cd + EDTA (1:0.4)‐solution was bound to high molecular weight proteins, as studied by gel‐filtration. II. Direct infusion into the stomach or the duodenum (under anaesthesia). About 10% of the administered Cd‐dose (60 mg=0.53 mmol Cd/kg b.wt.) was absorbed in the mice exposed to Cd alone (which was about 4 times more than what was seen after oral exposure via stomachtube, see below), resulting in a 100% mortality in these mice within 96 hours after exposure. After administration of 1:0.4‐solution the concentrations of cadmium in liver and kidneys (1 hour after exposure) were about twice as high as in the Cd‐exposed mice. However, cadmium given simultaneously with EDTA in the (1:4)‐ solution was not toxic. Five hours after exposure to Cd alone most cadmium was bound to high molecular weight proteins in liver and kidneys, while almost all Cd in the liver of mice exposed simultaneously to Cd and EDTA was bound to low molecular weight proteins, which indicates that cadmium is more rapidly absorbed from the gastrointestinal tract in the presence of EDTA. III. Oral exposure. Cadmium was found to be more toxic when administered alone (60 = 0.53 mmol Cd/kg b.wt.) than together with either concentrations of EDTA as shown by a higher mortality in the Cd‐exposed mice (75%) compared to the Cd + EDTA‐exposed animals (0%). Most Cd was bound to high molecular weight proteins in liver and kidneys in the Cd‐exposed mice (5 hours after exposure) while mice given Cd + EDTA had part of the cadmium also bound to low molecular weight proteins in the livers. No difference in the distribution of Cd among renal proteins were seen between mice from the various exposure groups. The complex formation of Cd (II) and EDTA in the present solutions was studied by a potentiometric method. Apart from the formation of a 1:1 Cd‐EDTA complex a binuclear Cd2‐EDTA complex was formed (accounting for about 35% of the total mol percent distribution of complexes) in the solution where an exess of cadmium with respect to EDTA was present. The results from the p...

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The Action of Inhalation Anesthetics on the Gastrointestinal Tract

Cited by 4 publications

References 106 publications

Effects of Chelating Agents on Oral Uptake and Renal Deposition and Excretion of Cadmium

Effects of Chelating Agents on Oral Uptake and Renal Deposition and Excretion of Cadmium

Effects of chelating agents on oral uptake and renal deposition and excretion of cadmium

Influence of Different Cd‐EDTA Complexes on Distribution and Toxicity of Cadmium in Mice after Oral or Parenteral Administration

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