Bile acid-induced liver toxicity: Relation to the hydrophobic-hydrophilic balance of bile acids

Attili, A.F.; Angélico, M.; Cantàfora, Alfredo; Alvaro, Domenico; Capocaccia, L.

doi:10.1016/0306-9877(86)90137-4

Cited by 259 publications

(148 citation statements)

References 35 publications

Supporting

Mentioning

138

Contrasting

Unclassified

Order By: Relevance

“…Therefore, it is suggested that the 6 ␣-or 12 ␣-hydroxylation reaction of dihydroxy bile acids may serve as an important regulator of hydrophobicity and the consequent detergent power of the enterohepatically cycling bile acids. 25 The present observation that this detoxification mechanism was impaired in severe acute hepatitis and liver cirrhosis is consistent with the general opinion that toxic bile acids play a role in both the intensification and the perpetuation of hepatocellular injury in acute and chronic liver diseases. 4,25 On the other hand, the successful use of liver transplantation in hepatic failure has created a need for early prognostic indicators to select patients at a time when liver transplantation is still feasible.…”

Section: Discussionsupporting

confidence: 92%

“…25 The present observation that this detoxification mechanism was impaired in severe acute hepatitis and liver cirrhosis is consistent with the general opinion that toxic bile acids play a role in both the intensification and the perpetuation of hepatocellular injury in acute and chronic liver diseases. 4,25 On the other hand, the successful use of liver transplantation in hepatic failure has created a need for early prognostic indicators to select patients at a time when liver transplantation is still feasible. For example, the criteria adopted in King' s College Hospital for liver transplantation in fulminant hepatic failure include the prothrombin time, serum bilirubin level, duration of jaundice before onset of encephalopathy and so on.…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

A Paucity of Unusual Trihydroxy Bile Acids in the Urine of Patients With Severe Liver Diseases

et al. 1999

View full text Add to dashboard Cite

To clarify the relationship between the occurrence of unusual trihydroxy bile acids, namely hyocholic acid, ursocholic acid (UCA), and ω‐muricholic acid (ω‐MCA) in urine and liver disease severity, urinary bile acids were analyzed by gas‐liquid chromatography in acute and late phases of acute hepatitis and before and after ursodeoxycholic acid (UDCA) loading in healthy adults and liver cirrhosis patients. In 11 patients with acute hepatitis, the occurrence rates and amounts of unusual trihydroxy bile acids were increased in the late (recovery) phase, as compared with those in the early phase. In 10 patients with severe acute hepatitis who had prothrombin times exceeding 16 seconds, these bile acids had completely disappeared from the urine in the early phase but reappeared in the late phase in those who had a good outcome, though never in a patient who died. After UDCA administration for a week, the amounts of unusual bile acids, especially UCA and ω‐MCA, which are thought to be synthesized through 12 α‐ and 6 α‐hydroxylations, respectively, from UDCA, were clearly increased in 10 healthy adults but only slightly changed in 10 patients with liver cirrhosis. In conclusion, hepatic hydroxylations of dihydroxy bile acids as a detoxification reaction were impaired in severe liver diseases, which may play a role in the intensification and perpetuation of hepatocellular injuries.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

A Paucity of Unusual Trihydroxy Bile Acids in the Urine of Patients With Severe Liver Diseases

et al. 1999

View full text Add to dashboard Cite

show abstract

“…It is accepted that hydrophobic bile acids such as deoxycholic acid show hepatocytotoxicity, and it has been suggested that this hepatocytotoxicity is associated with cholestatic change (Strange et al 1979;Attili et al 1986;Hofmann 1990). Hydrophobic bile acid, taurochenodeoxycholic acid-induced hepatotoxicity is attenuated by the antioxidant vitamin E (Sokol et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Although the pathogenesis of hepatic injury during cholestatic liver disease is not fully understood, accumulation of hydrophobic bile acids in the liver is considered to be an important contributing factor (Greim et al 1973;Attili et al 1986;Hofmann & Popper 1987). Deoxycholic acid, one of the hydrophobic bile acids, is a naturally occurring secondary bile acid that is generated from cholic acid by intestinal bacteria.…”

mentioning

confidence: 99%

“…Patel et al (1994) reported that hydrophobic bile acids caused apoptosis of rat hepatocytes. It has been suggested that hepatotoxicity induced by hydrophobic bile acids is associated with cholestatic change (Strange et al 1979;Attili et al 1986;Hofmann 1990). Bile duct ligation (Dueland et al 1991;Vitale et al 1992;Chen et al 1995), administration of estrogen (Meyers et al 1980;Adinolfi et al 1984), administration of chlorpromazine (Ros et al 1979) and a choline-deficient diet (Murray et al 1992) also induce cholestasis in rat livers.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Ebselen Protects against the Reduction in Levels of Drug‐Metabolizing Enzymes in Livers of Rats with Deoxycholic Acid‐Induced Liver Injury

Tanaka

Takezawa

Kumai

et al. 2002

Pharmacology & Toxicology

View full text Add to dashboard Cite

Ebselen is a seleno-organic compound that inhibits oxidative stress by lipid peroxidation through a glutathione peroxidase-like activity. We studied the effect of ebselen on the expression of hepatic drug-metabolizing enzymes in rats with deoxycholic acid-induced liver injury. Hydrophobic bile acids, such as deoxycholic acid, are known to cause cholestatic liver injury, and it was reported that expression of hepatic cytochrome P-450 (CYP) was reduced by deoxycholic acid administration in rats. Hydrophobic bile acids induce lipid peroxidation in the liver, and this may be one mechanism of the development of liver injury. In the present study, we investigated the effect of ebselen (30 mg/kg/day for 10 days) on rats ingesting deoxycholic acid (1% of diet for 10 days). Deoxycholic acid decreased levels of CYP1A1, 2B1, 2E1 and 3A2 to 34, 58, 62 and 37% of control values, respectively, and increased serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activities to 1.8 and 8.6 times the levels of controls, respectively. Administration of ebselen with deoxycholic acid prevented the decreases in levels of CYP1A1 and 3A2 (86 and 65% of control, respectively) and the increases in serum ALP and ALT activities (1.4 and 1.9 times of control, respectively) caused by deoxycholic acid. These results indicate that ebselen may have a protective effect against hydrophobic bile acid-induced liver injury.

show abstract

Effect of Bile on Growth, Peritoneal Absorption, and Blood Clearance of Escherichia coli in E coli Peritonitis

Andersson

Schalén²,

Tranberg³

1991

Arch Surg

View full text Add to dashboard Cite

The effect of intraperitoneal bile on growth, peritoneal absorption, and clearance of Escherichia coli was determined in E coli peritonitis in the rat. In E coli peritonitis, intraperitoneal bacterial counts gradually decreased, whereas they increased (after 2 hours) with subsequent development of bacteremia in E coli plus bile peritonitis. After an intraperitoneal injection of labeled bacteria, blood radioactivity was only initially lower in E coli plus bile peritonitis compared with E coli peritonitis. Clearance from blood was lower in E coli plus bile peritonitis than in E coli peritonitis. Organ localization was similar in E coli peritonitis and E coli plus bile peritonitis with decreased splenic, increased pulmonary, and unchanged hepatic uptakes compared with controls. Impaired peritoneal absorption of bacteria, together with impaired local host defense, is likely to enhance the noxious effect of bile in E coli peritonitis.

show abstract

Bile acid-induced liver toxicity: Relation to the hydrophobic-hydrophilic balance of bile acids

Cited by 259 publications

References 35 publications

A Paucity of Unusual Trihydroxy Bile Acids in the Urine of Patients With Severe Liver Diseases

A Paucity of Unusual Trihydroxy Bile Acids in the Urine of Patients With Severe Liver Diseases

Ebselen Protects against the Reduction in Levels of Drug‐Metabolizing Enzymes in Livers of Rats with Deoxycholic Acid‐Induced Liver Injury

Effect of Bile on Growth, Peritoneal Absorption, and Blood Clearance of Escherichia coli in E coli Peritonitis

Contact Info

Product

Resources

About