Dataset Information

Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models.

ABSTRACT:

Background/aims

Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects.

Methods

The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis.

Results

The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2.

Conclusion

The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

SUBMITTER: Kang SH

PROVIDER: S-EPMC9271712 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models.

Kang Seong Hee SH Yim Hyung Joon HJ Hwang Ji-Won JW Kim Mi-Jung MJ Lee Young-Sun YS Jung Young Kul YK Yim Hyungshin H Kim Baek-Hui BH Park Hae-Chul HC Seo Yeon Seok YS Kim Ji Hoon JH Yeon Jong Eun JE Um Soon Ho SH Byun Kwan Soo KS

The Korean journal of internal medicine 20220608 4

<h4>Background/aims</h4>Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects.<h4>Methods</h4>The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, ...[more]

PMID: 35811365

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Dataset Information

Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models.

Background/aims

Methods

Results

Conclusion

Publications

Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models.

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