Bile duct ligation

In the bile-duct-ligated rat, hepatic mitochondrial lipid peroxides are increased and correlate with serum levels of alkaline phosphatase, bilirubin and alanine aminotransferase (Sokol et al., 1991). Dietary vitamin E deficiency resulted in relatively higher lipid peroxide and bilirubin... 

Singh, S., Shackelton, G., Ah-Sing, E., Chakraborty, J. and Bailey, M.E. (1992). Antioxidant defenses in the bile duct-ligated rat. Gastroenterology 103, 1625-1629. 

Sokol, R.J., Devereaux, M. and Khandwala, R,A. (1991). Effect of dietary lipid and vitamin E on mitochondrial lipid peroxidation and hepatic injury in the bile duct-ligated rat. J. Lipid Res. 32, 1349-1357. 

Abbreviation. BDL, bile duct ligation. Source From Ref. 10. 

Klaassen CD. Comparison of the toxicity of chemicals in newborn rats to bile-duct ligated and sham operated rats and mice. Toxicol AppI Pharmacol 1974 24 37. 

L. Beljaars, K. Poelstra, G. Molema, and D. K. F. Meijer, Targeting of sugar- and charge-modified albumins to fibrotic rat livers The accessibility of hepatic cells after chronic bile duct ligation, J. Hepatol. 29 579-588 (1998). 

Wagner M, Fickert P, Zollner G, Fuchsbichler A, Silbert D, Tsybrovskyy O, Zatloukal K, Guo GL, Schuetz JD, Gonzalez FJ, Marschall HU, Denk H, Trauner M. Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice. Gastroenterology 2003 125 825-838. 

Poo, J.L., Feldmann, G., Erlinger, S., Braillon, A., Gaudin, C., Dumont, M., Lebrec, D. Ursodeoxychohc acid limits liver histologic alterations and portal hypertension induced by bile duct ligation in the rat. Gastroenterology 1992 102 1752-1759... 

Mayoral P, Criado M, Hidalgo F, Flores O, Arvelo MA, et al. 1990. Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation. Clin. Sci. 96 297-305... 

Several studies highlight the use of mdrl-knockout mice to investigate P-glyco-protein function in vivo [45, 46]. In bile duct-ligated mice, 16% of digoxin administered i.v. was secreted into the gut lumen of control animals, whereas only 2% was secreted in mdrl-knockout mice [47], This finding supports the earlier observations... 

The already mentioned proteins OCTI and OCT3 transport small cationic substances, such as tetraalkyl ammonium compounds, polyamines such as spermine, monoamino-neurotransmitters, or N-methyl-nicotinamide across the basolateral plasma membrane [56]. OCTs play a key role in the distribution of cationic drugs and, therefore, drug interactions at the transporter level may become clinically relevant, as compounds with high affinity, such as prazosin or phenox-ybenzamine, may affect the excretion of other substrates. Certain liver diseases or obstructive cholestasis may result in alterations of hepatic clearance via these transporters. In rats, a 7-day bile duct ligation resulted in a marked downregulation of Octi and an increased hepatic accumulation of the Octi substrate tetraethylammonium [57]. 

M., and ErJinger, S. (1997) Expression of the Jiver Na" "-independent organic anion transporting poJypeptide (oatp-1) in rats with bile duct ligation. Journal of Hepatology, 27 (6), 1051-1056. 

Hepatobiliary transporters are affected by both systemic inflammation (e.g., arising from an infection) and inflammation intrinsic to the liver (e.g., acute inflammatory cholestasis caused by drug or alcohol abuse). As described above, endotoxin or turpentine are used to trigger systemic inflammation in rodents. Other rodent models of cholangitis include ethinylestradiol (oral contraceptive-induced cholestasis/cholestasis of pregnancy), alpha-naphthylisocyanate (vanishing bile duct syndrome), and common bile duct ligation (extrahepatic biliary obstruction) [87, 88]. 

Fickert, P. et al. (2002) Ursodeoxycholic add aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via... 

F12. Fishman, W. H., Green, S., and Inglis, N. I., Decline in rat-serum alkaline phosphatase following bile-duct ligation. Biochim. Biophys. Acta 62, 429-431 (1962). 

K6. Kaplan, M. M., Induction of rat liver alkaline phosphatase by bile duct ligation. Yale J. Biol. Med. 52, 69-75 (1979). 

TABLE 2.2 Effect of bile duct ligation (BDL) on the toxicity of certain compounds... 

Sex differences were marked in the male all fractions contained higher proportions of i8-muricholate and lower percentages of chenodeoxycholate in the female larger amounts of deoxycholate and cholate appeared in cytosol, and greater quantities of lithocholate were found in cytosol and mitochondria. An increase of hepatic y8-muricholate from Q% in normal male rats to 72% of the bile acids after 8-10 days of bile duct ligation has been reported [12], The concentration of hepatic bile acids in neonatal rats (0-1 to 60 days) increased after birth with a concomitant increase in chenodeoxycholate and )8-muricholate and a decrease in cholate until the 60th day of life [13]. 

G.C. Farrell (1995). Downregulation of male-specific cytochrome P450s 2C11 and 3A2 in bile duct-ligated male rats Importance to reduced hepatic content of cytochrome P450 in cholestasis. Hepatology 22, 580-587. 

Huseby, N. E., and V. Torstein. 1978. The activity of gamma glutamyl transferase after bile duct ligation in guinea pig. Clinica Chimica Acta 88 385-392. 

In rats with bile duct ligation, administration of 0.4 g daily of an aqueous extract of Chinese salvia for 4 weeks significantly reduced histological grades of fibrosis and ameliorated the portal hypertensive state as compared with control. Treatment had no effect on plasma biochemical profiles of either bile duct ligated or normal rats (Huang etal.2001). 

Nan JX, Park EJ, Kim HJ, Ko G, Sohn DH (2000) Antifibrotic effects of the methanol extract of Polygonum aviculare in fibrotic rats induced by bile duct ligation and scission. Biol Pharm BuU 23(2) 240-243... 

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