Dehydrocholate sodium (Sodium dehydrocholate)

Effects of sodium ursodeoxycholate, hyodeoxycholate and dehydrocholate on cholesterol and bile acid metabolism in rats

Effects of sodium ursodeoxycholate, hyodeoxycholate and dehydrocholate on serum and liver cholesterol levels, bile flow, biliary cholesterol, phospholipid and bile acid secretions, and fecal sterol and bile acid excretions were examined with Wistar strain male rats fed ordinary and 2% cholesterol supplemented diets. Dehydrocholate increased the liver cholesterol level, bile flow and biliary lipid secretion, but ursodeoxycholate and hyodeoxycholate did not. The serum cholesterol level was not changed by the treatments. Ursodeoxycholate and hyodeoxycholate increased their own secretion into the bile and decreased cholic acid secretion, while dehydrocholate increased deoxycholic acid and oxo bile acid secretion. Ursodeoxycholate increased but dehydrocholate decreased the fecal sterol excretion, and hyodeoxycholate caused no change. Dehydrocholate decreased the fecal coprostanol level. The total amounts of the fecal bile acids were similar in all the treated groups, but ursodeoxycholate increased lithocholic acid, alpha, beta- and omega-muricholic acids and ursodeoxycholic acid; hyodeoxycholate increased hyodeoxycholic acid, 3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid and oxo bile acids; and dehydrocholate increased deoxycholic acid, cholic acid, omega-muricholic acid and oxo bile acids and decreased hyodeoxycholic acid. These data suggested that ursodeoxycholate was transformed into lithocholic and muricholic acids, and dehydrocholate into cholic and deoxycholic acids during the enterohepatic circulation, but hyodeoxycholate showed almost no change. Ursodeoxycholate and hyodeoxycholate caused neither accumulation of cholesterol in tissues nor increase in bile flow and biliary lipid secretion as well as chenodeoxycholate did. The biological effect of dehydrocholate was similar to that of cholate, and this was partially due to its conversion into cholic acid and deoxycholic acid.

Electroencephalographic consequences of sodium dehydrocholate-induced blood-brain barrier disruption: Part 2. Generation and propagation of spike activity after the topical application of sodium dehydrocholate

Sodium dehydrocholate was applied topically to the right hemispheric cortex of eight rats and the electrocorticogram was monitored from both the treated cortex and the homotopic cortex of the contralateral hemisphere. All animals developed blood-brain barrier (BBB) disruption in the treated cortex as evidenced by cortical staining with systemically administered Evans blue dye. Spike activity developed in three of eight animals after the topical application of dehydrocholate. The subsequent intravenous injection of sodium dehydrocholate provoked spike activity in both hemispheres in all eight animals. Dependent and independent spike activity was recorded in the nondisrupted hemisphere. The intravenous administration of gamma-aminobutyric acid (GABA) resulted in alterations in spike activity in four of five animals because of penetration of the GABA through the altered BBB. These findings demonstrate that sodium dehydrocholate can result in increased BBB permeability when applied directly to the cortical surface. Spike activity subsequent to the topical application of dehydrocholate can be enhanced by systemic loading with dehydrocholate. Spike activity occurring over the nontreated cortex (secondary focus) represents interhemispheric propagation of spike activity from the disrupted hemisphere (primary focus). The lack of Evans blue staining in the actively discharging secondary focus suggests that spike activity does not account for the increases in BBB permeability observed with dehydrocholate treatment.

Aqueous sodium dehydrocholate-sodium deoxycholate mixtures at low concentration

The behavior of the sodium dehydrocholate (NaDHC)-sodium deoxycholate (NaDC) mixed system was studied by a battery of methods that examine effects caused by the different components of the system: monomers, micelles, and both components. The behavior of the mixed micellar system was studied by the application of Rubingh's model. The obtained results show that micellar interaction was repulsive when the aggregates were rich in NaDHC. The gradual inclusion of NaDC in micelles led to a structural transformation in the aggregates and the interaction became attractive. The bile salts' behavior in mixed monolayers at the air-solution interface was also investigated. Mixed monolayers are monotonically rich in NaDC, giving a stable and compact adsorbed layer. Results have shown that the interaction in both micelles and monolayer is not ideal and such behavior is assumed to be due to a structural factor in their hydrocarbon backbone.

Electroencephalographic consequences of sodium dehydrocholate-induced blood-brain barrier disruption: Part 1. Acute and chronic effects of intracarotid sodium dehydrocholate

Prior work has shown that the intracarotid infusion of sodium dehydrocholate can produce prolonged reversible blood-brain barrier (BBB) disruption. Associated with barrier disruption is the occasional presence of behavioral seizure activity. Electroencephalographic changes were monitored in 32 rats after BBB disruption by the left internal carotid artery infusion of sodium dehydrocholate. The electroencephalogram (EEG) was monitored for 3 hours after disruption in 20 animals, and the remaining 12 animals were followed for 24 hours. The EEG was also monitored in 8 additional control animals: 4 had undergone carotid artery infusion with normal saline, and 4 had received sodium dehydrocholate intravenously. The 20 rats monitored for up to 3 hours postinfusion were found to have varying grades of BBB disruption as measured by the presence of Evans blue staining of the brain. EEG alterations in this group included decreased amplitude and slowing as well as the presence of spike activity over the disrupted and the nondisrupted hemispheres. The more extensive the disruption, the more severe the EEG changes. In animals with minimal to moderate disruption, the EEG usually returned to base line levels within 3 hours after infusion. Animals with marked disruption usually had bilaterally flat EEGs before the end of the observation period. The remaining 12 animals were followed for 24 hours postinfusion. Of 9 animals surviving 24 hours, 1 animal had a decrease in amplitude over the disrupted hemisphere; in the remaining 8 animals, the spontaneous EEG was unchanged from predisruption levels except for occasional spikes in 2 animals. Animals infused with intracarotid saline or intravenous sodium dehydrocholate demonstrated no EEG changes or Evans blue staining.(ABSTRACT TRUNCATED AT 250 WORDS)

The secretory characteristics of dehydrocholate in the dog: comparison with the natural bile salts

1. During dehydrocholate administration in the taurine replete dog, the maximum excretory rate of total bile salt (almost entirely dehydrocholate derivative, mostly conjugated) was 3-84 +/- 0-53 (S.D.) mumole/min. kg body wt. (eleven experiments). This was much less than the excretory maximum previously obtained for taurocholate (8-64 +/- 1-31 (S.D.) mumole/min. kg total cholate, mostly conjugated). 2. The superimposition of taurocholate infusion did not cause any significant change in the 'dehydrocholate' maximum but taurocholate itself was excreted into bile at no more than about half its normal maximum. When taurocholate maximum excretion was established first, it was reduced by dehydrocholate administration. In both types of experiment the joint bile salt excretory maximum was of the same order as that of taurocholate alone, provided taurocholate made up at least 40-50% of the total bile salt. 3. When taurocholate administration was stopped, the maximum excretory rate of 'dehydrocholate' rose to values up to 63% above the initially determined excretory maximum; the enhanced 'dehydrocholate' excretory maximum, when calculated for optimal conditions, approached that of actively conjugated vholate, even though the effective 'dehydrocholate' concentration in bile was ten to twenty times the critical micellar concentration of taurocholate. This suggests that the effective bile salt concentration in bile is not an important determinant of the secretory performance of a bile salt. 4. To explain findings (2) and (3) it is necessary to postulate that taurocholate has both a facilitatory and an inhibitory action on 'dehydrocholate' excretion. The facilitatory action, which persists after taurocholate has left the animal, may consist either of an increase in the maximum rate at which modification of dehydrocholate takes place within the liver cell, or an increase in the number of functioning 'carriers' for 'dehydrocholate' transfer. The data suggest that the inhibitory effect is due to the competitive interaction that also appears to exist between the two bile salts. 5. The increase in bile flow rate per unit increase in 'dehydrocholate' excretion (15 ml./m-mole) was about twice that obtained for taurocholate. There was no significant formation of micellar aggregates during 'dehydrocholate' excretion, as judged from the total electrolyte concentration of bile and its osmalality. 6. During the excretion of 'dehydrocholate'-taurocholate mixtures (approximately 1:1) at submaximal rates the associated bile flow rate was not less than the sum of the separate components, thus suggesting that 'dehydrocholate' was not being incorporated in taurocholate mixed micelles.