Bile acid excretion: the alternate pathway in the hamster.

Galeazzi, Renato L.; Javitt, Norman B.

doi:10.1172/jci108821

Cited by 63 publications

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“…UBA has also been analyzed in various animal species, such as hamsters (Galeazzi and Javitt, 1977), chimpanzees (Schweng et al, 1978), rabbits (Nakao et al, 1980), monkeys (Suzuki et al, 1985), and rats (Palmer, 1971; Takita et al, 1988;Lee et al, 2001). However, these studies focused on the alteration of metabolic ability of the liver and the pathogenic mechanisms of liver disease.…”

Section: Original Articlementioning

confidence: 99%

“…Recently, the direct enzymatic assay of urine sulfated bile acids (USBA) content was developed as a diagnostic tool (Matsui et al, 1996), and several reports revealed the clinical importance of USBA analysis (Obatake et al, 2002; Shinohara et al, 2005; Huang et al., 2007). Since a large portion of bile acids are sulfated in human urine (Palmer, 1967;Stiehl, 1974), USBA rather than non-sulfated UBA is useful in clinical application.UBA has also been analyzed in various animal species, such as hamsters (Galeazzi and Javitt, 1977), chimpanzees (Schweng et al, 1978), rabbits (Nakao et al, 1980), monkeys (Suzuki et al, 1985), and rats (Palmer, 1971; Takita et al, 1988;Lee et al, 2001). However, these studies focused on the alteration of metabolic ability of the liver and the pathogenic mechanisms of liver disease.…”

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Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats

et al. 2009

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-Estimation of liver damage is important in the pathophysiological and toxicological bile acids (UBA) in a rat model of liver disease. Thioacetamide (TAA)-treated rats were used in this study. Single intraperitoneal administration of high-dose TAA induces severe damage to the liver, and thus is used as a model of acute hepatitis. Continuous administration of low-dose TAA yields mild damand chronic administration of TAA was associated with a dose-dependent elevation of UBA. The elevation of UBA content correlated with the alteration of blood biochemical indicators, and UBA screening -with abnormal serum alkaline phosphatase (ALP) activity due to chronic liver damage, which was condemonstrated that measurement of UBA is a simple, non-invasive and effective method for the screening of cholestasis in TAA-treated rats. We suggest that UBA analysis may have potent applicability for monitoring the progress of liver damage in animal models of chronic liver disease, such as cirrhosis and hepatic encephalopathy.Bile acid, Urine, Liver, Cholestasis, Cirrhosis, ThioacetamideCorrespondence: Hiroshi Kawai (E-mail: hkawai@jiu.ac.jp) Original ArticleThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.34, No.1, 27-38, 2009 Vol. 34 No. 1 27 the systemic circulation is small. The blood concentration -tions, but is increased in the case of a disorder in the liver or biliary tract (Dawson, 2002). Therefore, the serum bile acid level is a marker of liver disease, although it is not widely used as a routine screening test.Urine bile acids (UBA) have been detected in patients with hepatic disease since the 1950s (Rudman and Kendall, 1957; Makino et al et al., 1976;Almé et al., 1977;Simko et al., 1987;Batta et al., 1989; Shoda et al acids has been carried out mainly by gas or liquid chromatography -mass spectrometry (GC-MS, LC-MS) in recent studies. GC-MS and LC-MS can identify various structurally different bile acids precisely, and alteration of the composition of UBA can be analyzed. These methods, however, require complicated sample preparation, a long period of time, and a well-disciplined technician. A more simple and rapid method is needed for routine screening or analysis of a large number of samples. Recently, the direct enzymatic assay of urine sulfated bile acids (USBA) content was developed as a diagnostic tool (Matsui et al., 1996), and several reports revealed the clinical importance of USBA analysis (Obatake et al., 2002; Shinohara et al., 2005; Huang et al., 2007). Since a large portion of bile acids are sulfated in human urine (Palmer, 1967;Stiehl, 1974), USBA rather than non-sulfated UBA is useful in clinical application.UBA has also been analyzed in various animal species, such as hamsters (Galeazzi and Javitt, 1977), chimpanzees (Schweng et al., 1978), rabbits (Nakao et al., 1980), monkeys (Suzuki et al., 1985), and rats (Palmer, 1971; Takita et al., 1988;Lee et al., 2001). However, these studies focused on the alteration of metabolic ability of the liver and the pathogenic mechanisms of liver disease...

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Section: Original Articlementioning

confidence: 99%

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Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats

et al. 2009

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“…3,4 While the balance of evidence suggests that this ordinarily is the major pathway for bile acid synthesis, [5][6][7][8] an alternate pathway initiated by sterol 27-hydroxylase in mitochondria also leads to the formation of primary bile acids via another enzymatic step catalyzed by oxysterol 7␣-hydroxylase. 9,10 Recent studies in mice deficient in cholesterol 7␣-hydroxylase showed that the induction of oxysterol 7␣-hydroxylase at about 3 weeks of age facilitates the generation of sufficient bile acid to support growth and development thereafter. 11 Irrespective of which pathway is involved in their synthesis, these acidic sterols are secreted via the bile into the lumen of the small bowel, where they mix with a pool of bile acids that undergoes continuous enterohepatic flux, and which plays a critical role in the absorption of lipids and fat-soluble vitamins.…”

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Gender-related differences in bile acid and sterol metabolism in outbred CD-1 mice fed low- and high-cholesterol diets

Turley¹,

Schwarz

Spady³

et al. 1998

Hepatology

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These studies were undertaken to determine whether in young adult outbred CD-1 mice there were any genderrelated differences in basal bile acid metabolism that might be important in determining how males and females in this species responded to a dietary cholesterol challenge. When fed a plain cereal-based rodent diet without added cholesterol, 3-month-old females, compared with age-matched males, manifested a significantly larger bile acid pool (89.1 vs. 54.1 mol/100 g body weight), a higher rate of fecal bile acid excretion (13.6 vs. 8.5 mol/d/100 g body weight), a more efficient level of intestinal cholesterol absorption (41.1% vs. 25.3%), and a lower rate of hepatic sterol synthesis (338 vs. 847 nmol/h/g). Similar results were found in C57BL/6 and 129Sv inbred mice. In matching groups of CD-1 mice fed a diet containing 1% cholesterol for 21 days, hepatic cholesterol levels increased much more in the females (from 2.4 to 9.1 mg/g) than in the males (from 2.1 to 5.2 mg/g). This occurred even though the level of stimulation of cholesterol 7␣-hydroxylase activity in the females (79%) exceeded that in the males (55%), as did the magnitude of the increase in fecal bile acid excretion (females: 262% vs. males: 218%). However, in both sexes, bile acid pool size expanded only modestly and by a comparable degree (females: 19% vs. males: 26%) so that in the cholesterol-fed groups, the pool remained substantially larger in the females than in the males (102.3 vs. 67.6 mol/100 g body weight). Together, these data demonstrate that while male and female CD-1 mice do not differ qualitatively in the way cholesterol feeding changes their bile acid metabolism, the inherently larger bile acid pool in the female likely facilitates the delivery of significantly more dietary cholesterol to the liver than is the case in males, thereby resulting in higher steady-state hepatic cholesterol levels. (HEPATOLOGY 1998;28:1088-1094.)The central role that the liver plays in the maintenance of whole-body sterol balance and the regulation of plasma low-density lipoprotein (LDL)-cholesterol levels stems partly from its unique ability to convert cholesterol to bile acids, the excretion of which represents a major route for the elimination of cholesterol from the body.

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“…The eluate of the sulfate fraction was concentrated in vacuo below 40°C. The residue was dissolved with 1.5 ml of solvolysis solution prepared with 2, 2-dimethoxypropane, water, and concentrated hydrochloric acid (7.5: 1.0 : 0.1 v/v) as described by Galeazzi and Javitt (1977). After sonication for ten minutes, the reaction mixture was incubated at 37°C under shaking in a water bath for three hours.…”

Section: Methodsmentioning

confidence: 99%

A enzymatic and fluorimetric determination of total bile acid sulfates in human urine.

Amakasu

Sano

Miyakawa

et al. 1986

Tohoku J. Exp. Med.

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A simple, precise and sensitive method for separation and determination of total bile acid sulfates in human urine is described. The sulfate fraction of urinary bile acids was separated with lipophilic anion exchange gel, piperidinohydroxypropyl Sephadex LH-20 after sample clean-up with Sep-Pak C18 cartridge. The obtained sulfate fraction was submitted to solvolysis with a small volume of dimethoxypropane-HC1 solution and subjected to enzymatic-fluorimetrical assay using 3a-hydroxysteroid dehydrogenase and resazurin. In this method, no influence of existing salts in the reaction mixture on fluorescence intensity was observed and solvolysis reaction was almost complete. Overall recoveries of glycine-and taurine-conjugated bile acid 3-sulfates from normal urine ranged from 90.5 to 93.7% and those of unconjugates from 48.7 to 78.0%. The sensitivity of the described method enabled to estimate total bile acid sulfates with 0.5 ml of normal urine and precision tests showed the satisfactory accurasy. The level of total urinary bile acid sulfates was estimated on some patients with hepatobiliary diseases and healthy subjects. bile acid sulfates ; 3a-hydroxysteroid dehydrogenase ; solvolysis ; piperidinohydroxypropyl Sephadex urine Since the sulfate ester of bile acid in man was initially described (Palmer 1967), the metabolic significance of bile acid sulfates in hepatobiliary diseases has been discussed by many investigators (Stiehl 1974;Stiehl et al. 1980Stiehl et al. , 1982Makino et al. 1975;Van Berge Henegouwen et al. 1976 ;Summerfield et al. 1977 ;Bremmelgaard and Sjovall 1979). The sulfate group enhances the water solubility of bile acids rendering them easy to excrete in the urine. From these facts, the role of sulfation is considered to be one of protection against the toxity of bile acids and measurement of bile acid sulfates in biological materials gives important information regarding bile acid metabolism in pathological situations. Although the determination of bile acid sulfates has been performed by gas-liquid chromatography or gas-liquid chromatography mass-spectrometry, these methods are not

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Bile acid excretion: the alternate pathway in the hamster.

Cited by 63 publications

References 28 publications

Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats

Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats

Gender-related differences in bile acid and sterol metabolism in outbred CD-1 mice fed low- and high-cholesterol diets

A enzymatic and fluorimetric determination of total bile acid sulfates in human urine.

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