It is intended to explore the mechanism involved in the development of membrane damages in the mitochondria of brain and liver tissues of rats given dicumarol (3, 3-methylene-bis (4-hydroxycoumarin) ) by assessing the effects of dicumarol administration on the activities of superoxide dismutase and ATPase which are intimately associated both with active transport of NaT and K+ and with electrical potential of neuronal membrane.
In this study the contents of inorganic phosphorus, gerneration rate of superoxide and the activities of ATPase, catalase and superoxide dismutase in the major organs of rats- to which dicumarol was administered orally were determined. In dicumarol-treated rats, body temperature increased(+1.9C), whereas body weight decreased(2. 4%) compared with control group.
The content of inorganic phosphorus and the generation rate of superoxide also increased in all tissues that obtained from animals administered this compound, especially these variations were the highest in the liver. The activity of ATPase in rats tissues was enhanced by the administration of dicumarol, but it did not induce the Na´, K+-ATPase or Mg+z-ATPase selectively. The activity of catalase in the liver of animals treated with dicumarol increased about 73% of control one, but in other tissues the increment of activity of catalase was not observed. The total activity of superoxide dismutase increased in all tissues of animals treated with dicumarol compared with control one, but the activity of cytosolic superoxide dismutase `vas slightly decreased, whereas mitochondrial superoxide dismutase activity was increased significantly.
These results indicated that uncoupling of the oxidative phosphorylation and of respiratory chain by dicumarol stimulates the generation of superoxide in the tissues. The action of those oxygen free radicals might have caused the swelling and destruction of mitochondrial membranes. However, a selective induction of Na*, K+-ATPase which may play an important role in the membrane potential was not observed in the all tissues of animals treated with this compound.
|