The protective role of hydrophilic tetrahydroxylated bile acids (THBA)

Sheps, Jonathan A.; Wang, Jianshe; Ling, Victor

doi:10.1016/j.bbalip.2021.158925

Cited by 8 publications

(13 citation statements)

References 117 publications

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“…Recently, it was shown that Mdr2- deficient mice that also lack Bsep have increased bile salt hydroxylation, and thus a more hydrophilic and less toxic bile salt pool, and also the total bile salt pool was reduced compared with that of the MDR2 KO. 24 , 25 Together, this resulted in protection against severe liver injury. Increased levels of bile salt polyhydroxylation does not seem to contribute to beneficial consequences of ASBT inactivation as ASBT KO mice have reduced plasma taurine-conjugated tetrahydroxylated and pentahydroxylated bile salts, and there is no increase in excretion of these bile salts in urine.…”

Section: Discussionmentioning

confidence: 99%

Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice

Kunst¹,

Waart²,

Wolters³

et al. 2022

JHEP Reports

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Section: Discussionmentioning

confidence: 99%

Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice

Kunst¹,

Waart²,

Wolters³

et al. 2022

JHEP Reports

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“…The current study establishes the relationship of Tetrahydroxy bile acids concentration, which represents an essential proportion of urinary bile acids in neonates and infants with infantile cholestatic hepatic disease, the neonates and infants with a good prognosis had an essential higher proportion Tetrahydroxy bile acids, as this study recommends that the percentage of Tetrahydroxy bile acids from total bile acids 30%-60% is a good prognosis disease, which means slower disease progression, but the percentage decreases in some cases of intra-and extra-hepatic cholestasis as this study assumes to less than 30% as represent in table (1) due to the other clinical evaluation symptoms from the presence of acholic stool and dark urine in poor prognostic patients and the absence of these symptoms in good prognostic patients, Tetrahydroxy bile acids more than 30% from total bile acids suggests patients are in a good prognosis of disease because Tetrahydroxy bile acids are highly hydrophilic in nature and excrete with urine and exist in human body mainly during the neonatal period (Sheps et al, 2021).…”

Section: Discussionmentioning

confidence: 95%

“…Tetrahydroxy bile acid is a hepatoprotective agent in alleviating cholestatic stress and of hydrophilic nature and low toxicity and exists with a most negligible concentration in adults, unlike in infants with intra-hepatic cholestasis, which have a high level in urine; it has been suggested to investigate the incidence of Tetrahydroxy bile acids in neonates and infants with infantile intra-and extra-hepatic cholestasis and tetrahydroxy bile acids association with their outcomes (Sheps et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Urinary tetrahydroxy bile acids investigation in infantile cholestasis

Al-Bassam¹

2022

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Background: Tetrahydroxy bile acids present at negligible or undetectable levels in healthy human adults but present at elevated levels in urine of infants with cholestasis clinically are the most valued marker of cholestasis next to serum tests. Methods: Twenty subjects with cholestasis, age range between seven days and one year, the study measured urinary tetrahydroxy bile acids for all cases. Results: Study found the presence of urinary tetrahydroxy bile acids in new-borns and infants with infantile cholestasis.New-borns and infants with a good prognosis had higher tetrahydroxy bile acids levels than those with a poor prognosis according to their outcomes. Conclusion:The study found the incidence of urinary tetrahydroxy bile acids in new-borns and infants with infantile intra-hepatic and extra-hepatic cholestasis. Extra-hepatic cholestatic patients had higher tetrahydroxy bile acids urine level than intra-hepatic, Cytomegalovirus and idiopathic neonatal hepatitis patients had a lesser tetrahydroxy bile acids level than in patients with genetic cholestasis. Tetrahydroxy bile acids play a role in clinical managing and treatment, in addition to their possible defensive properties against hepatic injury.

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“…Therefore, hydrophilic BAs such as tetrahydroxylated bile acids (THBAs) are more hepatoprotective and less toxic when compared with the usual BAs, which are typically di- or tri-hydroxylated. THBAs can inhibit BAs-induced liver injury in mice models [ 137 ].…”

Section: Bile Acids and Liver Cancer: Pathophysiologymentioning

confidence: 99%

Genetics in Familial Intrahepatic Cholestasis: Clinical Patterns and Development of Liver and Biliary Cancers: A Review of the Literature

Vitale

Mattiaccio

Conti

et al. 2022

Cancers

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The family of inherited intrahepatic cholestasis includes autosomal recessive cholestatic rare diseases of childhood involved in bile acids secretion or bile transport defects. Specific genetic pathways potentially cause many otherwise unexplained cholestasis or hepatobiliary tumours in a healthy liver. Lately, next-generation sequencing and whole-exome sequencing have improved the diagnostic procedures of familial intrahepatic cholestasis (FIC), as well as the discovery of several genes responsible for FIC. Moreover, mutations in these genes, even in the heterozygous status, may be responsible for cryptogenic cholestasis in both young and adults. Mutations in FIC genes can influence serum and hepatic levels of bile acids. Experimental studies on the NR1H4 gene have shown that high bile acids concentrations cause excessive production of inflammatory cytokines, resistance to apoptosis, and increased cell regeneration, all risk conditions for developing hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). NR1H4 gene encodes farnesoid X-activated receptor having a pivotal role in bile salts synthesis. Moreover, HCC and CCA can emerge in patients with several FIC genes such as ABCB11, ABCB4 and TJP2. Herein, we reviewed the available data on FIC-related hepatobiliary cancers, reporting on genetics to the pathophysiology, the risk factors and the clinical presentation.

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The protective role of hydrophilic tetrahydroxylated bile acids (THBA)

Cited by 8 publications

References 117 publications

Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice

Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice

Urinary tetrahydroxy bile acids investigation in infantile cholestasis

Genetics in Familial Intrahepatic Cholestasis: Clinical Patterns and Development of Liver and Biliary Cancers: A Review of the Literature

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