Conjugation of Non-Erythroid Bilirubin in Chronic Experimental Cholestasis in the Dog

Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated whether polyphenols from green tea Camellia sinenesis, which are potent free radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or a diet containing 0.1% polyphenolic extracts from C. sinenesis starting 3 days before bile duct ligation. After bile duct ligation, serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1–2 days, and fibrosis developed 2–3 wk after bile duct ligation. Additionally, procollagen-α1(I) mRNA increased 30-fold 3 wk after bile duct ligation, accompanied by increased expression of α-smooth muscle actin and transforming growth factor-β and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct ligation-dependent changes by 45–73%. Together, the results indicate that cholestasis due to bile duct ligation causes liver injury by mechanisms involving oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and prevent activation of stellate cells, thereby minimizing liver fibrosis.

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Plasma Concentrations in Methyl Isobutyl Ketone-Potentiated Experimental Cholestasis after Inhalation or Oral Administration

Toxicological Sciences ◽

10.1093/toxsci/21.2.222 ◽

1993 ◽

Vol 21 (2) ◽

pp. 222-227

Author(s):

ALEXANDRA B. DUGUAY ◽

GABRIEL L. PLAA

Keyword(s):

Oral Administration ◽

Methyl Isobutyl Ketone ◽

Plasma Concentrations ◽

Methyl Isobutyl ◽

Isobutyl Ketone ◽

Experimental Cholestasis

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Poster Session 1: Experimental Cholestasis

Hepatology ◽

10.1002/hep.27499 ◽

2014 ◽

Vol 60 ◽

pp. 401A-407A

Keyword(s):

Poster Session ◽

Experimental Cholestasis

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Induction of liver microsomal monooxygenases in experimental cholestasis

Bulletin of Experimental Biology and Medicine ◽

10.1007/bf00797553 ◽

1976 ◽

Vol 81 (4) ◽

pp. 509-512

Author(s):

N. E. Zakharova ◽

V. A. Mordvinov ◽

I. B. Tsyrlov ◽

V. V. Lyakhovich

Keyword(s):

Microsomal Monooxygenases ◽

Experimental Cholestasis

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Lipid metabolism in experimental cholestasis

Biochemical Journal ◽

10.1042/bj1240056pa ◽

1971 ◽

Vol 124 (5) ◽

pp. 56P-56P ◽

Cited By ~ 4

Author(s):

C O Record ◽

K G Alberti ◽

D H Williamson

Keyword(s):

Lipid Metabolism ◽

Experimental Cholestasis

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Dopaminergic inhibition of secretin-stimulated choleresis by increased PKC-γ expression and decrease of PKA activity

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00302.2002 ◽

2003 ◽

Vol 284 (4) ◽

pp. G683-G694 ◽

Cited By ~ 45

Author(s):

Shannon Glaser ◽

Domenico Alvaro ◽

Tania Roskams ◽

Jo Lynne Phinizy ◽

George Stoica ◽

...

Keyword(s):

Nervous System ◽

Bile Duct ◽

Intrahepatic Bile Duct ◽

Mechanisms Of Action ◽

Dopaminergic Receptors ◽

Inhibitory Effects ◽

Pkc Isoforms ◽

Camp Levels ◽

Experimental Cholestasis

To determine the role and mechanisms of action by which dopaminergic innervation modulates ductal secretion in bile duct-ligated rats, we determined the expression of D1, D2, and D3 dopaminergic receptors in cholangiocytes. We evaluated whether D1, D2 (quinelorane), or D3 dopaminergic receptor agonists influence basal and secretin-stimulated choleresis and lumen expansion in intrahepatic bile duct units (IBDU) and cAMP levels in cholangiocytes in the absence or presence of BAPTA-AM, chelerythrine, 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine (H7), or rottlerin. We evaluated whether 1) quinelorane effects on ductal secretion were associated with increased expression of Ca2+-dependent PKC isoforms and 2) increased expression of PKC causes inhibition of PKA activity. Quinelorane inhibited secretin-stimulated choleresis in vivo and IBDU lumen space, cAMP levels, and PKA activity in cholangiocytes. The inhibitory effects of quinelorane on secretin-stimulated ductal secretion and PKA activity were blocked by BAPTA-AM, chelerythrine, and H7. Quinelorane effects on ductal secretion were associated with activation of the Ca2+-dependent PKC-γ but not other PKC isoforms. The dopaminergic nervous system counterregulates secretin-stimulated ductal secretion in experimental cholestasis.

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