LIVER FIBROSIS AND CIRRHOSIS MODELS

Delivering translatability in liver fibrosis and cirrhosis models.

Liver fibrosis is caused by long term insult to hepatic tissues. Conditions that can lead to fibrosis include, but aren’t limited to chronic alcohol and drug abuse and viral hepatitis (B and C). Liver fibrosis, when left untreated, ultimately develops into liver cirrhosis, a condition notorious for its insidious onset. Liver cirrhosis eventually impairs liver function (leading often to portal hypertension), and also increases the risk of hepatocellular carcinoma (HCC) development. Till today, liver cirrhosis has no cure. This entire process takes anywhere between 15 to 20 years to develop, but for us at PharmaLegacy, every second counts when looking for potential cures and treatments.

And when time is of the essence, you can count on us. Our team of experts in pharmacology have spent more than 15 years perfecting our different models. Keep scrolling to check them out, and if you can’t find what you’re looking for, rest assured: we make custom made models as well.

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Liver Fibrosis & Cirrhosis

MODELS / SERVICES

Prevention CCl4 Study - Plasma ALT and AST Levels

Prevention CCl4 Study - HYP & Sirius Red Staining Quantitation

Therapeutic CCl4 Study – Plasma ALT and AST and TBIL levels

Therapeutic CCl4 Study – Sirius Red Staining Quantitation

Therapeutic CCl4 Study – Inflammation Score by H&E Staining

Prevention Study in Rats - Body Weight and Liver Weight (g)

Prevention Study in Rats - Serum Levels of ALT, AST and TBIL

Prevention Study in Rats - Histological Evaluation

Prevention Study in Mice - Body weight (g)

Prevention Study in Mice - Serum Levels of ALT (U/L)

PharmaLegacy Models and Research Tools

Case Study - CCl4-induced Liver Fibrosis and Cirrhosis Model

The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in blood increase with the duration of administration; a number of biomarker expressions are significantly increased in the liver at the end of 8 weeks. The hyperplasic nodules, surrounded by the fibrous bands, that are positively stained by Sirius Red are clearly formed in the liver at 16 weeks, but are ameliorated by Compound A treatment. (n=6, *P<0.05, **P<0.01 vs Vehicle by Bonferroni multi-comparison test)

Efficacy Studies for Drug Compounds/Candidates:

·         Serum biochemical endpoints

·         Fibrotic grade evaluation in liver

·         Quantification of fibrotic tissue in liver (Sirius red)

·         Quantification of SMA-α positive cells

·          Incidence and volume of ascites

Molecular Pharmacology for Proof of Concept Studies:

·          Vitality of activated primary stellate cells

·          Morphological alterations of the hepatocytes

·          Hepatic hydroxyproline, hepatic/serum glutathione, malondialdehyde (MDA) content

·          Expression of cyclins, PCNA, Ki67 and BrdU for regeneration of hepatocytes

Molecular Pharmacology for Proof of Concept Studies:

·         Angiogenesis inhibitors

·         Angiotensin receptor antagonists

·         Vasoactive modulators

·         hepatic vasculature analysis by immunostaining of anti-vWF, VEGF-A, angiopoietin-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

PharmaLegacy Models and Research Tools

Case: BDL-induced Liver Fibrosis / Cirrhosis in Rats

BDL-Induced Liver Cirrhosis: Hepatic Hydroxyproline (HYP) Content Quantitation

BDL-Induced Liver Cirrhosis: BDL Liver Histology (H&E Staining)

BDL-Induced Liver Cirrhosis: BDL Liver Histology (H&E Staining)

The morphological changes seen in the BDL model include bile duct proliferation, dilatation, and infiltration of inflammatory cells. At week 7, most hepatic lobules were replaced by the proliferated bile ducts and fibrous tissue.

BDL-Induced Liver Cirrhosis: BDL Liver Histology (Sirius Red Staining)

Hepatic fibrosis developed at week 1 after BDL, and increased in the following weeks. At week 7, portal-portal and portal-central were connected by fibrous tissue, and even hepatic lobules were replaced by fiber deposition.

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  • Completed over 400 FDA / CFDA IND filings
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  • 120,000 square feet of vivarium space

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