Abstract
Introduction: Influence of the endogenous opioid system on the liver has not been studied enough. To understand the damaging effects of stress on the liver and the hepatoprotective effects of opioids, a study was performed on stress-re- sistant and stress-susceptible animals.
 Materials and methods: The investigation was performed on 725 Wistar male-rats. Various types of stress were mod- eled: acute immobilization stress of various duration (3, 6 and 12 hours), chronic stress of limited mobility, swimming stress and traumatic stress (resection of 70% of the liver). Agonists of various types of opioid receptors in equimolar doses were injected to stressed animals at equimolar doses: DAGO – a mu-receptor agonist – at a dose of 6.3 mcg/kg, DSLET – a delta-receptor agonist – at a dose of 10 mcg/kg, and kappa receptor agonist dynorphin A (1-13) – at a dose of 20.1 mcg/kg.
 Results and discussion: The stress-limiting action of the studied opioids is characterized by the reduced hepatocyte dystrophy, microcirculation correction, a decreased concentration of lipid peroxidation metabolites, a suppressed cy-tolytic syndrome, a stimulated synthetic ability of the liver, and is more pronounced in stress- susceptible animals.
 The greatest stress-protective effect is shown after administering dynorphin A (1-13) in immobilization stress, and DAGO – in swimming stress. Dynorphin A (1-13) and DAGO manifested the most pronounced effect on the liver regeneration after resection. A preliminary stress simulation accelerates liver regeneration at the initial stage after re- section.
 Conclusion: The hepatoprotective effect of opioids in stress depends on the typological peculiarities of animals. The results obtained offer a challenge of synthesizing new hepatoprotectors.
Highlights
Influence of the endogenous opioid system on the liver has not been studied enough
Simulation of a 3-hour immobilization stress increased in the content of intermediate and final lipid peroxidation (LPO) metabolites in plasma only 39 hours after the end of exposure: the concentration of MDA increased 2.5 times (p
The data of the present study confirm the development of dystrophic changes in hepatocytes and impaired intrahepatic microcirculation
Summary
To understand the damaging effects of stress on the liver and the hepatoprotective effects of opioids, a study was performed on stress-resistant and stress-susceptible animals. Results and discussion: The stress-limiting action of the studied opioids is characterized by the reduced hepatocyte dystrophy, microcirculation correction, a decreased concentration of lipid peroxidation metabolites, a suppressed cytolytic syndrome, a stimulated synthetic ability of the liver, and is more pronounced in stress- susceptible animals. Dynorphin A (1-13) and DAGO manifested the most pronounced effect on the liver regeneration after resection. Conclusion: The hepatoprotective effect of opioids in stress depends on the typological peculiarities of animals. Solin AV et al.: Hepatoprotective effect of opioid peptides in stress people to stress is the functioning of stress-mediating and stress-limiting systems (Pshennikova 2003). The development of stress is accompanied by the inhibition of microsomal reductases, a disruption of hydroxylation, and disturbed synthesis of coenzymes
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