Biomedical subjects
Publications and source records attributed to F P Pel'kis.
The toxic and antitumor effects of cisplatin were shown to depend upon the activity of microsomal oxidation system enzymes. Administration of the drug in combination with K-2-9 enterosorbent was followed by an increase in its antitumor effect and amelioration of toxicity.
The K-2-9 preparation was determined to change cis-platinum pharmacokinetics, that resulted in its pharmacodynamics alterations. The higher Pt concentrations in the blood of animals which were given the K-2-9 preparation provided selectivity of cytostatic accumulation in the tumour tissue, that was accompanied by more prolonged inhibition of the DNA synthesis. A decrease in the toxicity of cis-platinum is associated with a change in the elimination pathway and acceleration of its removal from the organism.
It is determined that the organism may adapt in principle to alkylating antitumour preparations, to thiophosphamide in particular, being administered for a long time. The development of cell adaptation reactions in the systems of hemopoiesis and microsomal oxidation of hepatocytes is studied. An increase in the activity of enzymes of the microsomal liver oxidation system is found as accompanied by a lower concentration of 35S-thiophosphamide in the studied tissues and blood serum. The reactivity of tissue and serum SH-groups is observed to decrease with the organism adaptation to the preparation.
The effect of complex-forming sorbent K-2-9 on cisplatin toxicity was studied experimentally. Simultaneous treatment with the preparations was shown to lower the nephro- and gastroenterotoxicity of cisplatin did not detract from the antitumor effect of cisplatin.
The effect of interferon (IF) on the activity of multipurpose hepatic oxidases (MHO) in animals in the process of metastatic tumour development as well as interaction of IF and vinblastine (VBL) in the cell culture have been studied. IF activates MHO under conditions of their inhibition at the beginning of the tumour development and inhibits them to the normal level under activation in the postmetastatic period. Contrary to the data obtained in vivo IF does not decrease the toxicity of VBL for the tumour cells in vitro. The data obtained evidence for the modulating effect of IF on the MHO system under the tumour development.
It is established that the preparation K-2-9 being administered in combination with cis-dichlorodiaminoplatinum (DDP) lowers the DDP toxic effects, in particular nephrotoxicity and enterotoxicity, increases the activity of the enzymes participating in microsomal liver oxidation, the activity of kidney transamidinase, the quantity of SH-groups of the liver and kidney tissue, intensifies the antitumour effect of DDP.
A combined administration of cis-dichlorodiaminoplatinum (DDP) and phenobarbital increases the activity of nonspecific oxidases, decreases the toxic effect of DDP especially its nephrotoxic action, but does not decrease the antiblastic action of DDP in rats. On the basis of experimental data the optimum regime of DDP repeated administrations is suggested.
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