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V K Brovtsyn

Publications and source records attributed to V K Brovtsyn.

13 recordsLinked to original sources

The prevention of cisplatin-induced renal dysfunction by hydroxyl-containing dithiocarbamates.

Two hydroxyl containing dithiocarbamates, sodium N-methyl-D-glucamine dithiocarbamate (NaG) and sodium dihydroxyethyl dithiocarbamate (NaY) have been examined as agents for the control of the renal dysfunction in rats given cisplatin. Of these, NaG was found to be the more effective in controlling such renal dysfunction when administered at 1 and 3 h after 5 mg cisplatin kg-1, i.p. Renal function was examined 5 days after the administration of cisplatin by measurement of serum and urinary levels of creatinine and urea, creatinine clearance, serum and urinary levels of Na+, K+, Mg2+, Ca2+, as well as the concentrations of these ions in the renal medulla and cortex. Treatment of rats given cisplatin with NaG at 1 and 3 h post cisplatin resulted in indices of renal function which were not significantly different from those of animals which had received no cisplatin. The sole difference was found to be a slight increase in renal cortical Na+ concentration.

Animals↗

Cisplatin: nephrotoxic action in vertebrates and its prevention.

1. The kidney of frog and black sculpin appeared to be much less sensitive to the toxic action of CP in comparison with rat and pigeon. 2. The impairment of renal function after CP administration resulted in increased serum urea in rat, uric acid in pigeon and magnesium in black sculpin. 3. Kidney swelling is important feature of CP nephrotoxicity in rat and pigeon but not in frog and fish. 4. Pretreatment with choline chloride, PAH, furosemide and ethacrynic acid reduced the nephrotoxic action of CP in rat but did not prevent the accumulation of platinum in renal tissue which appeared to be a function of the dose injected to investigated animals.

Animals↗

[Characteristics of the action of cisplatin and cycloplatam on the rat kidney].

On the 5th day after intraperitoneal injection of cisplatin the rats developed renal insufficiency. The concentration of creatinine and urea in blood serum increased 9-fold, the glomerular filtration rate decreased 7.7-fold, the weight of kidney increased by 44%. The content of tissue sodium was found to increase, while that of K to decrease. The intraperitoneal injections of cycloplatam (up to 25 mg/kg) induced in rats no renal insufficiency, the kidney weight and the ion and water content in the tissue did not change. In the experiments with cisplatin the Pt level in kidney reached 59.1 +/- 3.05 micrograms/g dry substance, after the injection of cycloplatam 25 mg/kg it was 104.9 +/- 2.95. No nephrotoxic action of cycloplatam may be due to the presence in the molecule of the cyclopentyl substitute.

Animals↗

Effect of methotrexate on the pharmacokinetics and renal excretion of cisplatin.

The kinetics of platinum in plasma and erythrocytes, and its renal excretion, have been examined in five patients with non-small cell carcinoma of the lung, after treatment with cisplatin 50 mg/m2 (Platidiame) and, three weeks later, a combination of 50 mg/m2 cisplatin and 40 mg/m2 methotrexate. The patients were given 0.9% saline 1 l 1 h prior to drug application. Plasma platinum elimination was biphasic with a short initial phase (t1/2 alpha 10-31 min) and a long beta-phase (t1/2 beta 65-91 h). With the exception of increased AUC values in all five patients 0-8 h after the injection, no significant change in the kinetics of platinum in plasma was found after coadministration of methotrexate. In four of the five patients renal platinum excretion was reduced in the first 6 h after administration of methotrexate. The renal clearance of platinum was 50% lower in those four patients 0-3 h after the injection. With the exception of one patient, no signs of nephrotoxicity were observed after combined drug administration. Other toxic effects were mild and showed no increase after the initial administration of methotrexate.

Adult↗

[Activation analysis with reactor and 14 MeV neutrons in an experimental study of oxoplatinum].

The authors described a procedure of the instrumental neutron activation analysis of biomedical material on reactor and 14 MeV neutrons for determination of the platinum, silicon, chlorine, phosphorus, sodium and zinc content using the anticompton system of detection together with a programmed analyser and an automatic sample changer. The procedure was tested on rat small intestinal samples within the interval of 10 min-30 days after a single i. v. administration of oxoplatinum (15 mg per 1 kg of the animal body mass). Platinum redistribution with relative concentration maximum on the 15th day was noted. Changes in the phosphorus, chlorine, sodium and silicon content within the interval of 3-30 days were suggestive of a possible toxic effect of oxoplatinum metabolites during this period. In a clinical application of oxoplatinum one should take into account a possible toxic effect of metabolites in a long-term period after repeated administration of the agent.

Activation Analysis↗

[Neutron activation analysis in modelling the elimination from the kidneys of cis-dichlorodiammineplatinum].

A neutron activation analysis was used for a study of platinum elimination from the kidneys of male rats after administration of cis-DDP at a dose of 7 mg per 1 kg of the animal body mass. The literature data on beagles were taken for comparison. A simple mathematical model for platinum elimination from the kidneys was proposed: the platinum content was 2.27 micrograms per 1 g of raw tissue for the time interval of 3h less than or equal to t less than or equal to 1 day; 2.34 X X t(-0,51) micrograms/g for t greater than 1 day and a dose of 1 mg per 1 kg of the animal body mass. An opportunity to predict the platinum content in the human kidneys was tested.

Activation Analysis↗

The antitumor activity of oxoplatinum.

A coordination complex cis-dichlorodiamminedihydroxoplatinum (IV) (oxoplatinum) was first synthesized in the USSR by Chugaev and Khlopin in 1927 [3]. Its marked antitumor properties were revealed by one of the authors of this article at the All-Union Cancer Research Center of the Academy of Medical Sciences of the USSR. The paper gives data on the antiblastic and side effects of oxoplatinum and also on the results of pharmacokinetic studies of the drug. Particular attention was paid to the similarity and differences of biological properties of oxoplatinum and cis-dichlorodiammineplatinum(II) (DDP) which has found wide use in oncological practice. It has been established that, on principle, oxoplatinum differs from DDP in action on the body and tumors. The new drug is 10 times less toxic than DDP. Oxoplatinum has a wide spectrum of antineoplastic action resulting in marked inhibition of growth of solid and ascitic forms of transplantable tumors. The drug has a longer duration of antitumor effect after the end of the therapeutic course. An important property of oxoplatinum is its high therapeutic index. The new drug manifests high antitumor activity with different ways of its administration into the body. Oxoplatinum in therapeutic doses does not produce necrotic lesions in the kidneys. The new drug exerted no cross-resistance with DDP and the alkylating antitumor agent sarcolysin. At the present time oxoplatinum is undergoing preclinical investigation.

Animals↗

[Characteristics of the disorder in the composition of the internal medium and kidney function of vertebrate animals after cisplatin administration].

In rats, 5 days after injection of cisplatin (5 mg/kg of body weight) the urea content of the blood serum significantly increased; in pigeons, elevation of the uric acid was observed. No significant changes were found in the blood serum of the frog Rana temporaria even after injection of 40 mg/kg of cisplatin. In the black sculpin Myoxocephalus scorpius, injections of 50 mg/kg of cisplatin resulted in hypermagnesemia. Swelling of the kidney and changes in its electrolyte content were observed in rats, pigeons, and frogs, the wet weight of the kidney increased in rats and pigeons. In all the animals, accumulation of platinum in the kidney was observed, its content being dependent on the injected dose. The data obtained reveal lower sensitivity of the kidney in cold blood vertebrates to toxic effect of cisplatin and demonstrate that the pattern of disturbances in composition of the blood serum is related to the extent of the excretory function of the kidney within the species.

Animals↗