Abstract

The state of the mitochondrial megapore (mitochondrial permeability transition pore-mPTP), respiration and oxidative phosphorylation of rat liver and pancreas mitochondria in streptozotocin (STZ) - induced diabetes were studied, considered the ways of correction of the detected membrane damage with the flavone luteolin isolated from the plant Inula caspica. It was shown that, under conditions of experimental diabetes mellitus, the rate of swelling of rat liver and pancreas mitochondria is higher than of the healthy ones; this means that mPTP of rat liver and pancreas mitochondria is in the open state in pathology. Luteolin recovers mPTP to the normal condition, thus removing the effect of STZ on mitochondria. It was also shown that, the respiration rate of liver and pancreatic mitochondria in the state 3 and state 4 states increases in STZ - induced diabetes, which significantly reduces the respiratory control (RC) and ADP/O coefficients in comparison with the control. The data obtained indicate the disconnection of respiration and oxidative phosphorylation in STZ - induced diabetes. Luteolin (oral dose is 50 mg/kg of body weight, during 8 days) eliminates the detected functional disorders of rat liver and pancreas mitochondria, probably due to its antioxidant properties.

Highlights

  • Study of cells’ structural and functional damage mechanisms in pathology and methods of correcting these injuries with the help of pharmacological agents is a priority of modern endocrinology

  • The aim of this work was to study the mechanisms of damage to mPTP, the respiratory and phosphorylating functions of liver and pancreatic mitochondria in STZinduced diabetes, as well as the possibility of correcting the detected disorders with the help of luteolin

  • Under the experimental conditions we used, the swelling of mitochondria can be considered as a result of the open state of mPTP and the suppression of swelling, as closed, i.e. using this technique, it is possible to assess the state of mPTP in STZ-induced diabetes and the action of luteolin

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Summary

Introduction

Study of cells’ structural and functional damage mechanisms in pathology and methods of correcting these injuries with the help of pharmacological agents is a priority of modern endocrinology. In spite of the variety of means for diabetes mellitus treatment, the search for novel pharmacological targets in demand In the cell, such “targets” are mitochondrial membranes and structures localized in them, primarily the respiratory chain and mPTP) [1, 2]. The formation of reactive oxygen species in the cell and the excessive activation of free radical oxidation processes underlie the development of diabetes mellitus [4, 5]. These processes are considered as a universal mechanism that unites the main biochemical pathways of the toxic effect of hyperglycemia on the body. It is known that the mitochondrial respiratory chain is the main source of reactive oxygen species [6]

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