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Liver Diseases

PharmaLegacy has developed and validated a serials of liver disease models, including liver fibrosis/cirrhosis models, NASH, acute hepatitis and liver regeneration models, to test pharmacological effects and mechanisms of candidate drugs. 



Animal models

    Fulminant Hepatitis

            - Fas Ab (Jo2)-induced liver failure

            - Acetaminophen intoxication

 

    Immune Response Related Hepatitis

            - Con A-induced liver injury

            - LPS-GalN-induced fulminant hepatitis

 

    Liver Injury Regeneration

            - Partial hepatectomy

            - Bile duct ligation-induced liver fibrosis and cirrhosis

            - ANIT-induced cholestasis and fibrosis

            - Fas Ab (Jo2)-induced liver regeneration

            - CCl4 -induced liver regeneration

 

    ◇Liver Steatosis

            - Alcohol-induced fatty liver

            - Non-alcohol steatohepatitis (NASH)

 

    ◇Liver Fibrosis and Cirrhosis

            - CCl4 -induced liver fibrosis and cirrhosis

            - CCl4 -induced acute liver injury and fibrogenesis

            - Bile duct ligation-induced liver fibrosis and cirrhosis 

            - ANIT-induced cholestasis and fibrosis 


    ◇Hepatitis β 

         - C57 BL/6J-Tg (AlblHBV) 44Bri/Jf4J transgenic mice model

         - M-TgHBV transgenic mice model



Endpoints


        Efficacy studies for drug compounds/candidates: 
         • Serum biochemical endpoints  
         • Fibrotic grade evaluation in liver  
         • Quantifi cation of fi brotic tissue in liver (Sirius red)  
         • Quantifi cation of SMA-α positive cells  
         • Incidence and volume of ascites  
 

        Molecular pharmacology for proof of concept studies:  
         • Vatality of activated primary stellate cells  
         • Morphological alterations of the hepatocytes  
         • Hepatic hydroxyproline, hepatic/serum glutathione, MDA content  
         • Expression of cyclins, PCNA, Ki67 and BrdU for regeneration of hepatocytes  
 

        Mechanistic investigation:
          Angiogenesis inhibitors
         Angiotensin receptor antagonists 
          Vasoactive modulators
          Hepatic vasculature analysis by immunostaining of anti-vWF

          VEGF-A,  angipoietin-1, angiopoietin-2, placental growth factor

          VCAM-1, ICAM-1 expression; CD11b, CD3, CD31 expression 
          Apoptosis of activated hepatic stellate cells 


        Bio-marker analysis of involved signaling pathways