Plasma alkaline phosphodiesterase I in intrahepatic cholestasis induced by α-naphthylisothiocyanate in rats

1. Administration of α-naphthylisothiocyanate (ANIT) to rats produced dose-dependent increases in plasma bile acid and bilirubin concentrations. Similar increases in plasma bile acid and bilirubin concentrations were evident in bile duct ligated rats, indicating that the severity of cholestasis is almost identical in both models. 2. Plasma alkaline phosphodiesterase I was increased by only 50–80% while alkaline phosphatase was increased more than threefold after ANIT administration. This is in contrast to an earlier study [S. R. Simpson, K. Rahman & D. Billington (1984) Clinical Science 67, 647–652] where, after bile duct ligation, serum alkaline phosphodiesterase I was elevated sixfold before any increase in alkaline phosphatase activity became apparent. Thus, plasma alkaline phosphodiesterase I does not offer as sensitive a marker of intrahepatic cholestasis (induced by ANIT) as it does of extrahepatic cholestasis (induced by bile duct ligation). 3. Hepatic alkaline phosphodiesterase I was unaffected by ANIT pretreatment while hepatic alkaline phosphatase was increased up to seven times. It is suggested that raised plasma alkaline phosphodiesterase I is due to regurgitation of the biliary enzyme rather than overspill of the enzyme from liver into blood. 4. Gel filtration showed that 24 h and 96 h after ANIT administration, rat serum contained a high molecular weight form of alkaline phosphodiesterase I, suggesting a different isoenzyme profile.

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Serum Alkaline Phosphodiesterase I in Experimental Biliary Obstruction in the Rat

Clinical Science ◽

10.1042/cs0670647 ◽

1984 ◽

Vol 67 (6) ◽

pp. 647-652 ◽

Cited By ~ 1

Author(s):

Stuart R. Simpson ◽

K. Rahman ◽

D. Billington

Keyword(s):

Alkaline Phosphatase ◽

Bile Duct ◽

Biliary Obstruction ◽

Bile Duct Ligation ◽

Serum Alkaline Phosphatase ◽

Gel Filtration ◽

Rat Serum ◽

Duct Ligation ◽

Rat Bile ◽

Molecular Weight Form

1. Alkaline phosphodiesterase I was present in rat liver at approx. 100-fold greater activity than alkaline phosphatase, and in rat bile at approx. 25-fold greater activity. 2. Rat serum alkaline phosphodiesterase I was increased 6-fold whilst serum alkaline phosphatase was increased only 2-fold 96 h after bile duct ligation. 3. In contrast to alkaline phosphatase, hepatic alkaline phosphodiesterase I was not affected by bile duct ligation, suggesting its raised serum activity was due to bile regurgitation rather than overspill of the enzyme from liver into blood. 4. Gel filtration showed that 8 and 96 h after bile duct ligation the serum contained a high molecular weight form of alkaline phosphodiesterase I. 5. It is suggested that alkaline phosphodiesterase I offers a potentially useful indicator of biliary obstruction in the rat.

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Decline in rat-serum alkaline phosphatase following bile-duct ligation

Biochimica et Biophysica Acta ◽

10.1016/0006-3002(62)90277-9 ◽

1962 ◽

Vol 62 (2) ◽

pp. 429-431 ◽

Cited By ~ 10

Author(s):

William H. Fishman ◽

Sidney Green ◽

Norma I. Inglis

Keyword(s):

Alkaline Phosphatase ◽

Bile Duct ◽

Bile Duct Ligation ◽

Serum Alkaline Phosphatase ◽

Rat Serum ◽

Duct Ligation

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Vitamin A Supplementation Alleviates Extrahepatic Cholestasis Liver Injury through Nrf2 Activation

Oxidative Medicine and Cellular Longevity ◽

10.1155/2014/273692 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Guiyang Wang ◽

Peng Xiu ◽

Fu Li ◽

Cheng Xin ◽

Kewei Li

Keyword(s):

Bile Duct ◽

Liver Injury ◽

Liver Function ◽

Vitamin A ◽

Western Blotting ◽

Bile Duct Ligation ◽

Retinyl Palmitate ◽

Binding Activity ◽

Extrahepatic Cholestasis ◽

Duct Ligation

Aim. To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats.Methods. Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays.Results. Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1.Conclusion. Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.

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Disturbed structural interactions between microfilaments and tight junctions in rat hepatocytes during extrahepatic cholestasis induced by common bile duct ligation

Histochemistry and Cell Biology ◽

10.1007/s004180050078 ◽

1996 ◽

Vol 106 (6) ◽

pp. 573 ◽

Cited By ~ 1

Author(s):

Ji-Ying Song ◽

J. Van Marle ◽

Cornelis J. F. Van Noorden ◽

W. M. Frederiks

Keyword(s):

Bile Duct ◽

Common Bile Duct ◽

Tight Junctions ◽

Bile Duct Ligation ◽

Rat Hepatocytes ◽

Common Bile Duct Ligation ◽

Extrahepatic Cholestasis ◽

Duct Ligation ◽

Structural Interactions

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Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats

Biochemical Journal ◽

10.1042/bj2800373 ◽

1991 ◽

Vol 280 (2) ◽

pp. 373-377 ◽

Cited By ~ 82

Author(s):

S Dueland ◽

J Reichen ◽

G T Everson ◽

R A Davis

Keyword(s):

Bile Acid ◽

Bile Duct ◽

Liver Function ◽

Urinary Excretion ◽

Bile Acids ◽

Bile Duct Ligation ◽

Microsomal Cytochrome ◽

Duct Ligation ◽

Cytochrome P 450

We examined how total blockage of biliary excretion, the major pathway through which cholesterol and bile acids are removed from the body, affects liver function, cholesterol and bile acid metabolism and homoeostasis. After 4 weeks of bile-duct ligation, rats showed impaired liver function, as documented by elevations in serum bilirubin and alkaline phosphatase activity. Moreover, bile-duct ligation decreased by about 30% both the amount of microsomal cytochrome P-450 in the liver and the elimination of aminopyrine in vivo, a reliable index in vivo of microsomal mixed-function oxidase activity. Cholesterol and bile acid contents in livers of bile-duct-ligated rats were doubled compared with sham-operated controls. Despite the increase in the contents of cholesterol and bile acids in liver, activities of the respective rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, were doubled. Serum concentrations of bile acids and free cholesterol increased 25- and 4-fold respectively. The large increase in serum bile acids was associated with a 380-fold increase in the urinary excretion of bile acids. Although there is a general decrease in cytochrome P-450 content and drug metabolism involving cytochrome P-450-containing hydroxylases, the activity of cholesterol 7 alpha-hydroxylase, also a cytochrome P-450-containing enzyme, is actually increased. These data show that complete obstruction of the bile duct results in the selective impairment of microsomal cytochrome P-450. Increased activity of 7 alpha-hydroxylase, bile acid synthesis and urinary excretion provides an alternative excretory pathway that helps to maintain cholesterol homoeostasis when the biliary excretory pathway is eliminated.

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