Effects of secretin on TCDCA- or TDCA-induced cholestatic liver injury in the rat

Murakami, Fujio; Tateishi, Aiko; Itoh, Yuka; Sakaida, Isao; Okita, Kiwamu

doi:10.1016/s1386-6346(01)00141-3

Cited by 12 publications

(14 citation statements)

References 24 publications

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“…Intravenous administration of TCDCA at low micromolar concentrations causes cholestasis in bile fistula rats (12,17). In our model, 25 M TCDCA markedly decreased bile flow and organic anion secretion, suggesting that the cholestatic effect of this bile acid is mainly independent of a cytotoxic effect.…”

mentioning

confidence: 54%

Phosphatidylinositol 3-kinase-dependent signaling modulates taurochenodeoxycholic acid-induced liver injury and cholestasis in perfused rat livers

Rust

Bauchmüller²,

Fickert³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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mentioning

confidence: 54%

Phosphatidylinositol 3-kinase-dependent signaling modulates taurochenodeoxycholic acid-induced liver injury and cholestasis in perfused rat livers

Rust

Bauchmüller²,

Fickert³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Thus, secretin‐induced trafficking of vesicles in the cholangiocytes is the key mechanism by which secretin exerts its effects to increase the secretion of water, bicarbonate, and electrolytes as well as the absorption of biliary bile acids. Aside from these, secretin may also enhance excretion of cytotoxic bile acids in animals having cholestasis, 122 and dose‐dependently inhibits motility of the proximal and distal segments of the bile duct component of the sphincter of Oddi in order to regulate bile flow into the duodenum 123 …”

Section: Introductionmentioning

confidence: 99%

Secretin: A Pleiotrophic Hormone

Chu

Yung

Chow

2006

Annals of the New York Academy of Sciences

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Secretin holds a unique place in the history of endocrinology and gastrointestinal physiology, as it is the first peptide designated as a hormone. During the last century since its first discovery, the hormonal effects of secretin in the gastrointestinal tract were extensively studied, and its principal role in the periphery was found to stimulate exocrine secretion from the pancreas. Recently, a functional role of secretin in the brain has also been substantiated, with evidence suggesting a possible role of secretin in embryonic brain development. Given that secretin and its receptors are widely expressed in multiple tissues, this peptide should therefore exhibit pleiotrophic functions throughout the body. The present article reviews the current knowledge on the central and peripheral effects of secretin as well as its therapeutic uses.

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“…Concurrent with liver injury, TBAs, especially the dominant types of bile acids 41 and the t-CBAs, markedly increased in the livers after rats were treated with high-dose of Geniposide. Among t-CBAs, TCDCA and taurodeoxycholic acid (TDCA) have postulated as inducers of cholestasis that significantly elevate serum levels of ALT and AST in rats 44 . Additionally, TCA, TCDCA and TDCA are substantially elevated in acetaminophen-induced acute liver failure patients 45 .…”

Section: Discussionmentioning

confidence: 99%

Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation

Tian

Zhu

et al. 2017

Sci Rep

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Fructus Gardenia (FG), containing the major active constituent Geniposide, is widely used in China for medicinal purposes. Currently, clinical reports of FG toxicity have not been published, however, animal studies have shown FG or Geniposide can cause hepatotoxicity in rats. We investigated Geniposide-induced hepatic injury in male Sprague-Dawley rats after 3-day intragastric administration of 100 mg/kg or 300 mg/kg Geniposide. Changes in hepatic histomorphology, serum liver enzyme, serum and hepatic bile acid profiles, and hepatic bile acid synthesis and transportation gene expression were measured. The 300 mg/kg Geniposide caused liver injury evidenced by pathological changes and increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamytransferase (γ-GT). While liver, but not sera, total bile acids (TBAs) were increased 75% by this dose, dominated by increases in taurine-conjugated bile acids (t-CBAs). The 300 mg/kg Geniposide also down-regulated expression of Farnesoid X receptor (FXR), small heterodimer partner (SHP) and bile salt export pump (BSEP). In conclusion, 300 mg/kg Geniposide can induce liver injury with associated changes in bile acid regulating genes, leading to an accumulation of taurine conjugates in the rat liver. Taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) as well as tauro-α-muricholic acid (T-α-MCA) are potential markers for Geniposide-induced hepatic damage.

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Effects of secretin on TCDCA- or TDCA-induced cholestatic liver injury in the rat

Cited by 12 publications

References 24 publications

Phosphatidylinositol 3-kinase-dependent signaling modulates taurochenodeoxycholic acid-induced liver injury and cholestasis in perfused rat livers

Phosphatidylinositol 3-kinase-dependent signaling modulates taurochenodeoxycholic acid-induced liver injury and cholestasis in perfused rat livers

Secretin: A Pleiotrophic Hormone

Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation

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