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ONO-5046, an elastase inhibitor, attenuates liver mitochondrial dysfunction after endotoxin
1Department of Anesthesiology, University of Hirosaki School of Medicine, Aomori, Japan.
Critical Care Medicine
|January 15, 1998
Summary
ONO-5046, an elastase inhibitor, improved liver mitochondrial function and blood pressure in endotoxin-induced shock in guinea pigs. This suggests ONO-5046 may protect against endotoxin-induced liver damage.
Area of Science:
- Biochemistry
- Pharmacology
- Physiology
Background:
- Endotoxemia can cause severe liver mitochondrial dysfunction.
- Elastase plays a role in the inflammatory response during endotoxemia.
Purpose of the Study:
- To evaluate the efficacy of ONO-5046, an elastase inhibitor, in mitigating liver mitochondrial dysfunction following endotoxin administration.
- To assess the impact of ONO-5046 on physiological parameters during endotoxin shock.
Main Methods:
- A prospective, randomized, controlled animal study was conducted using male Hartley guinea pigs.
- Endotoxin shock was induced via intravenous lipopolysaccharide (LPS) infusion.
- Animals were treated with varying doses of ONO-5046 or saline post-LPS administration.
Main Results:
- ONO-5046 demonstrated dose-dependent improvements in liver mitochondrial oxidative phosphorylation, including oxygen uptake, respiratory control ratio, and ATP synthesis.
- The drug also improved the adenosine 5'-diphosphate/oxygen (ADP/O) ratio and arterial ketone body ratio.
- The highest dose of ONO-5046 (30 mg/kg/hr) significantly improved mean blood pressure in endotoxemic guinea pigs.
Conclusions:
- ONO-5046 effectively attenuates endotoxin-induced liver mitochondrial dysfunction.
- The protective effects of ONO-5046 may be linked to improved liver blood flow.
- Elastase inhibition presents a potential therapeutic strategy for managing endotoxemia.
