Olprinone, a Selective Phosphodiesterase III Inhibitor, Has Protective Effects in a Septic Rat Model after Partial Hepatectomy and Primary Rat Hepatocyte

Masaya Kotsuka ¹, Tetsuya Okuyama ¹, Yuki Hashimoto ¹

⁰Department of Surgery, Kansai Medical University, Hirakata 573-1010, Japan.

International Journal of Molecular Sciences +

|

July 13, 2024

View abstract on PubMed

Summary

Olprinone (OLP), a heart failure drug, shows hepatoprotective effects by reducing inflammation and liver injury after surgery. OLP suppresses key inflammatory pathways, improving survival in endotoxin-induced liver damage models.

Area Of Science

Pharmacology
Hepatology
Immunology

Background

Olprinone (OLP) is a phosphodiesterase III inhibitor used for heart failure.
Its hepatoprotective effects, especially after liver resection, are largely unknown.
Endotoxin-induced liver injury models are crucial for studying liver damage mechanisms.

Purpose Of The Study

To investigate the hepatoprotective potential of Olprinone (OLP) in rat models.
To elucidate the mechanisms underlying OLP's effects on endotoxin-induced liver injury post-hepatectomy.
To assess OLP's impact on inflammatory mediators and nuclear factor kappa B (NF-κB) activation.

Main Methods

In vivo: Rats underwent 70% partial hepatectomy and lipopolysaccharide (LPS) treatment (PH/LPS).
In vitro: Primary cultured rat hepatocytes were treated with interleukin-1β (IL-1β).
OLP administration, survival rates, mRNA expression (TNF-α, CXCL1, iNOS), NF-κB activity, and pathological liver damage were assessed.

Main Results

OLP increased survival rates by 85.7% in the PH/LPS model.
OLP significantly decreased mRNA expression of inflammatory mediators (TNF-α, CXCL1, iNOS).
OLP suppressed NF-κB activation and nuclear translocation, reducing liver damage and neutrophil infiltration. It also inhibited IL-1β-stimulated iNOS induction in vitro.

Conclusions

Olprinone (OLP) demonstrates significant hepatoprotective effects against endotoxin-induced liver injury following hepatectomy.
OLP's mechanism involves suppressing inflammatory mediator induction via inhibition of NF-κB activation.
These findings suggest OLP's potential therapeutic value in preventing liver injury after liver resection.

Keywords:

acute liver injury inducible nitric oxide synthase nuclear factor kappa B olprinone partial hepatectomy with lipopolysaccharide primary cultured hepatocytes