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Statins May Improve Liver Fibrosis
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Reported by Jules Levin
EASL, April 2007, Barcelona, Spain
"COMPRARISON OF TWO STATINS EFFICACY ON A REVERSIBILITY OF EXPERIMENTAL RAT LIVER FIBROSIS"
O. Lukivskaya 1, Yu. Popov 2, J. Zaks 2, D. Schuppan 2, V. Buko 1
1 Department Of Hepatology, Institute Of Pharmacology And
Biochemistry, Grodno, Belarus; 2 Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA, USA
Background/Aims: Previous data indicate that statins may have antifibrotic properties independently of its lipid-lowering efficacy. Currently, nothing is known on efficiacy of these drugs to reverse liver fibrosis. The aim of this study was to assess and compare the effects of two statins, fluvastatin (FLU) and simvastatin (SIM) in rat model of thioacetamide (TAA)-induced liver fibrosis reversal.
Materials and Methods: Advanced liver fibrosis was induced by TAA treatment (200 mg/kg, i.p.) twice a week for 12w. Resolution of fibrosis was assessed after 2 months of TAA withdrawal. During this period, fibrotic rats were daily administered with FLU (10 mg/kg) and SIM (5 and 10 mg/kg) by oral gavage. The severity of liver fibrosis and degree of its reversal was assessed by morphometric evaluation of liver slides stained with Azan-Mallory, hydroxyproline (Hyp) determination and mRNA the steady state levels of procollagen I, MMP-13 and TIMP-1 as assessed by QRT-PCR using the TaqMan technique.
Results:
The TAA treatment resulted in advanced fibrosis/cirrhosis with complete fibrous septa formation and dramatic increase in liver hydroxyproline (Hyp) content, procollagen I, TIMP-1 and MMP-13 mRNA expression. These signs were significaltly impaired in rats with TAA withdrawal. Only treatment with high dose SIM (10 mg/kg) significantly decreased the square of liver connective tissue stained by Azan-Mallory compared to the vehicle-treated group, whereas no
significant reversion was observed in rats treated with low dose SIM (5 mg/kg) and FLU (10mg/kg). The tested statins did not changed tota and relative HYP content in the liver. Interestingly, both doses of SIM increased hepatic levels of interstitial collagenase (MMP-13) mRNA expression, while FLU did not.
Conclusion:
Our study suggests that statins with similar lipid-lowering properties may have a different antifibrotic activity. Simvastatin, but not Fluvastatin demonstrated a moderate antifibrotic effect in a model of TAA-induced liver fibrosis reversal. This is likely due to a difference in MMP-13 induction.
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