Formation of lamellar bodies in rat liver mitochondria in hyperthyroidism.

In the present work, ultrastructural changes of rat liver mitochondria in hyperthyroidism were studied. Hyperthyroidism was induced in male Wistar rats by daily administration of 100 µg thyroxin per 100 g body weight for 5 days. The level of triiodothyronine and thyroxine increased 3- and 4-fold, respectively, in comparison with the same parameters in the control group, indicating the development of hyperthyroidism in experimental animals. It was found that under this experimental pathology 58% of the mitochondria are swollen, with their matrix enlightened, as compared to the control. In 40% of the profiles, the swollen mitochondria in the liver under hyperthyroidism exhibited rounded mono- or multilayer membrane structures, called lamellar bodies (LBs), presumably at different stages of their development: from the formation to the release from the organelles. Most LBs were located in the mitochondria near the nuclear zone (27%), while their number was reduced in the part of the cell adjacent to the plasma membrane. In a number of swollen mitochondria the cristae were shown to change their orientation, being directed radially toward the center of the mitochondria. We suggested that it is the first stage of formation of LBs. The second stage can be attributed to the formation of monomembrane structures in the center of the organelles. The third stage is characterized by the fact that the membrane of the lamellar bodies consists of several layers, and in this case the bodies were located closer to the outer mitochondrial membrane. The evagination of the outer mitochondrial membrane and its connection with lamellar structure can be recognized as the fourth stage of formation of LBs. At the fifth stage the developed lamellar formations exited the mitochondria. At the same time, following the exit of LBs from the mitochondria, no damage to the mitochondrial membrane was registered, and the structure of the remaining part of the mitochondria was similar to the control. The nucleus of the hepatocyte also underwent structural changes in hyperthyroidism, exhibiting changes in the membrane configuration, and chromatin condensation. The nature and structure of the LBs, as well as their functional role in the liver mitochondria in hyperthyroidism, require further investigation.

Functioning of the mitochondrial ATP-dependent potassium channel in rats varying in their resistance to hypoxia. Involvement of the channel in the process of animal's adaptation to hypoxia.

The mechanism of tissue protection from ischemic damage by activation of the mitochondrial ATP-dependent K(+) channel (mitoK(ATP)) remains unexplored. In this work, we have measured, using various approaches, the ATP-dependent mitochondrial K(+) transport in rats that differed in their resistance to hypoxia. The transport was found to be faster in the hypoxia-resistant rats as compared to that in the hypoxia-sensitive animals. Adaptation of animals to the intermittent normobaric hypoxia increased the rate of transport. At the same time, the intramitochondrial concentration of K(+) in the hypoxia-sensitive rats was higher than that in the resistant and adapted animals. This indicates that adaptation to hypoxia stimulates not only the influx of potassium into mitochondria, but also K(+)/H(+) exchange. When mitoK(ATP) was blocked, the rate of the mitochondrial H(2)O(2) production was found to be significantly higher in the hypoxia-resistant rats than that in the hypoxia-sensitive animals. The natural flavonoid-containing adaptogen Extralife, which has an evident antihypoxic effect, increased the rate of the mitochondrial ATP-dependent K(+) transport in vitro and increased the in vivo tolerance of hypoxia-sensitive rats to acute hypoxia 5-fold. The involvement of the mitochondrial K(+) transport in the mechanism of cell adaptation to hypoxia is discussed.