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Acidic Sphingomyelinase Inhibition Limits CCl 4 Induced Hepatic Fibrosis
Author(s) -
Quillin Ralph Cutler,
Wilson Gregory,
Nojima Hiroyuki,
Wang Jiang,
Schuster Rebecca,
Blanchard John,
Edwards Michael,
Gulbins Erich,
Lentsch Alex
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.387.5
Subject(s) - cirrhosis , acid sphingomyelinase , fibrosis , hepatic stellate cell , hepatic fibrosis , steatosis , medicine , chemistry , pharmacology , endocrinology , sphingomyelin , cholesterol
Existing evidence suggests that acidic sphingomyelinase (ASMase) controls hepatic stellate cell activation and may contribute to fibrosis. The objective of this study was to determine if the pharmacologic inhibition of ASMase limits CCl 4 induced hepatic fibrosis. C57BL/6 mice were given intraperitoneal injections of CCl 4 for 8 weeks to induce fibrosis. Some animals received amitriptyline in their drinking water to inhibit ASMase activity. Liver sections were examined and fibrosis stage (0–4) was scored. Treatment with CCl 4 generated significant hepatic fibrosis after week 4 (3.0 ± 0 vs. 1.2 ± 0.3) and week 6 (3.6 ± 0.2 vs. 1.3 ± 0.2) when compared to vehicle. Hepatic cirrhosis (stage 4 fibrosis) was induced after 8 weeks of CCl 4 treatment compared to vehicle (3.83 ± 0.41 vs. 0.67 ± 1.0, p<0.05). Inhibition of ASMase caused a significant decrease in hepatic collagen deposition at week 4 (2 ± 0), week 6 (2 ± 0) and week 8 (2.5 ± 0.3) when compared to CCl 4 treatment (p<0.05 for each). These data suggest that inhibition of ASMase may be a therapeutic target in hepatic fibrotic disorders and may prevent the progression to cirrhosis.