Cholestasis: human disease and experimental animal models

Rodríguez-Garay, Emilio A.

doi:10.1016/s1665-2681(19)32126-x

Cited by 113 publications

(51 citation statements)

References 66 publications

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“…This model is widely used to study the pathogenetic mechanisms of hepatic damage involved and possible therapeutic interventions in this condition [29]. We demonstrated in the present study, for the first time, that administration of leflunomide reduced significantly the hepatic dysfunction and damage caused by BDL of the rat liver.…”

Section: Discussionsupporting

confidence: 62%

Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment

et al. 2006

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Cholestasis, or impaired bile flow, occurs in a wide variety of liver diseases and causes hepatic damage by retention and accumulation of toxic hydrophobic bile salts inducing persistent inflammation and oxidative stress. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and anti-inflammatory agent against autoimmune disease, on hepatic damage produced by double ligature of the extrahepatic biliary duct in Wistar Albino rats. Cholestasis was done by double ligature and section of the extrahepatic biliary duct (BDL). Leflunomide was given i.g. 10 mg/kg/day. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and levels of direct bilirubin. Malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO), catalase (CAT) and superoxide dismutase (SOD) were determined to the oxidative status in the liver tissue. Myeloperoxidase (MPO) activity and levels of tissue hydroxyproline (HPR) were determined to neutrophil activation and collagen accumulation, respectively. Further, histological changes were studied. Treatment with leflunomide markedly reduced serum transaminase activities as compared to BDL rats. At the same time leflunomide significantly inhibited increases in liver MDA, PC and NO levels and also attenuated the depletion of CAT and SOD in the liver after bile duct ligation. Similarly, increase in tissue MPO activity and HPR due to BDL was also attenuated by leflunomide treatment. These findings were supported by histopathological findings. These findings suggested that leflunomide can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress and inflammatory process.

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Section: Discussionsupporting

confidence: 62%

Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment

et al. 2006

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“…A wide spectrum of clinical diseases, including gallstone impaction, sclerosing cholangitis, cholangiocarcinoma or compression of the common bile duct by pancreatic tumours or enlarged lymph nodes can impede bile secretion and manifest as cholestatic liver damage [1,2]. Bile acid accumulation in the portal tract provokes a prominent inflammatory process in which Kupffer cells increase formation of pro-inflammatory mediators, such as interleukin-1 (IL-1), tumour necrosis factor-a (TNF-a) and CXC chemokines in the liver [3,4].…”

Section: Introductionmentioning

confidence: 99%

P-selectin glycoprotein ligand-1-mediated leukocyte recruitment regulates hepatocellular damage in acute obstructive cholestasis in mice

et al. 2009

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“…Experimental intrahepatic cholestasis induced by 17α-ethynylestradiol (EE) is a widely used in vivo animal model used to examine the molecular mechanisms involved in estrogen-induced cholestasis (17). In EE-induced cholestasis, the expression of transporters is generally reduced in association with impaired biliary secretory function.…”

Section: Introductionmentioning

confidence: 99%

Reduced Antidiabetic Effect of Metformin and Down-regulation of Hepatic Oct1 in Rats with Ethynylestradiol-Induced Cholestasis

et al. 2008

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Cholestasis: human disease and experimental animal models

Cited by 113 publications

References 66 publications

Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment

Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment

P-selectin glycoprotein ligand-1-mediated leukocyte recruitment regulates hepatocellular damage in acute obstructive cholestasis in mice

Reduced Antidiabetic Effect of Metformin and Down-regulation of Hepatic Oct1 in Rats with Ethynylestradiol-Induced Cholestasis

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