Publication: Role of nitric oxide in the regulation of fibrogenic
factors in experimental liver fibrosis in mice
Authors
Leung, Tung-Ming ; Fung, Man-Lung ; Liong, Emily C. ; Lau, Thomas Y.H. ; Nanji, Amin A. ; Tipoe, George L.
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Publisher
Murcia: F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Previously, we have shown that an increased
expression level of iNOS but a reduction in the
expression of eNOS is associated with increased
oxidative stress markers in CCl4-induced experimental
liver fibrosis. The present study aimed to investigate the
effect of L-arginine and 5-methylisothiourea hemisulfate
(SMT) in the expression of profibrogenic factors in
chronic liver injury. ICR mice were treated with CCl4
with or without treatment of L-arginine, an NO donor, or
SMT, an iNOS inhibitor. The expression of matrix
metalloptroteinases (MMPs), tissue inhibitors of
metalloproteinases (TIMPs), α-smooth muscle actin (α-
SMA), tumor necrosis factor-α (TNF-α) and
cyclooxygenase-2 (COX-2) were investigated by RTPCR.
The activity of the MMP-2 and MMP-9 were
measured by zymography. Our results showed that CCl4-
treated mice showed significant up-regulation of
expression of pro-fibrogenic factors, TNF-α and COX-2.
Treatment with L-arginine or SMT showed a significant
reduction in CCl4-induced expression of these profibrogenic
factors, TNF-α and COX-2. In conclusion,
both SMT and L-arginine effectively attenuated the
progression of CCl4-induced liver fibrosis. SMT
suppresses iNOS mediated NO production. However, Larginine
augments NO production. The similar effect of
the two drugs on liver fibrosis indicates that there may
be two distinct pathways of NOS mediated fibrogenesis
in chronic liver injury by iNOS and eNOS. Our results
suggest that eNOS-mediated liver fibrogenesis may play
a more important role than that of iNOS in chronic liver
injury. Taken together, these results support the contention that NO plays an active role in the
progression of liver fibrosis and hepatocellular damage.
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