The effect of hydroxyl-containing dithiocarbamates on cisplatin-induced long-term renal dysfunction in Wistar rats.

The possibility of a slow, longer term deterioration in renal function following the administration of cisplatin has been little studied in animal models. To obtain data on this we have examined renal function and histopathology at 30 days post i.p. cisplatin (5 mg/kg) treatment in female Wistar rats with and without the administration of hydroxyl-containing dithiocarbamates as a protective measure. In contrast to the studies terminated at shorter times, the degree of protection furnished by the use of dithiocarbamates at longer times post-treatment is less impressive. Results suggest that a continuing deterioration in renal function occurs at times greater than 1 week post-treatment when such dithiocarbamates are administered at 1 and 3 h post cisplatin. This was evidenced in both several measures of renal function and in the histopathology of the S3 segment of the proximal tubule.

[Possibilities for Ellman reaction application in the presence of detergents]. / Vozmozhnosti primeneniia reaktsii Ellmana v prisutstvii detergentov.

Triton X-100, triton X-305, twin-80 and sodium deoxycholate in definite concentrations lower the colour intensity of the solution which contains the product of the Ellman reaction. In the case of triton X-100 the colour disappearance is due to resynthesis of the Ellman reagent from 5-thio-2-nitrobenzoate with the presence of detergent in the concentration which is higher than the critical concentration of micelle-formation.

[Effect of amiloride on the activity of membrane-bound and soluble Na+-,K+-ATPase preparations]. / Vliianie amilorida na aktivnost' membranosviazannogo i rastvorimogo preparatov Na+-,K+-ATPazy.

Amiloride (8 X 10(-4), an inhibitor of sodium channels of nonexcited membranes, inhibits the activity of Na+,K+-ATPase in the kidney cortex homogenate as well as that of the partially purified membrane-bound and lubrol-soluble Na+,K+-ATPase preparations from the cattle brain. Inhibition of Na+,K+-ATPase from different organs of various animals by amiloride, a blocker of sodium channels, indicates similarity of the molecular organization of the Na+-recognizing component both of sodium channels and sodium centres of Na+,K+-ATPase.

[Effect of vasopressin on the osmotic permeability of the bladder wall in the frog and its content of cAMP, cGMP and inositol triphosphate]. / Vliianie vazopressina na osmoticheskuiu pronitsaemost' stenki mochevogo puzyria liagushki i soderzhanie v nei tsAMF, tsGMF i inozittrifosfata

An increase in the water permeability of the frog urinary bladder due to vasopressin, correlates with an increase of cAMP content in the bladder tissue. The osmotic permeability reached its maximum in 15-20 min. The sharp increase of inositol triphosphate content was observed within 20 sec after vasopressin administration, whereas cGMP content significantly decreased within 5 min. The augmentation of cAMP content seems to lead to a rise in water permeability white inositol triphosphate and cGMP acted, probably, as modulators of the vasopressin effect.

[Effect of ionophores A 23187 and valinomycin on acetyocholinesterase activity in rabbit erythrocytes]. / Vliianie ionofora A23187 i valinomitsina na aktivnost' atsetilkholinésterazy éritrotsitov krolika.

Activity of cholinesterase was higher in young erythrocytes when the cell populations of various age were studied; the enzymatic activity was increased after addition of valinomycine into a medium independently on the antibiotic concentration and the enzyme activation was more pronounced in the old population of erythrocytes. The same alterations were observed in presence of calcium ionophore A 23187 and nystatin. Alterations in the enzymatic activity appear to depend on changes of erythrocyte membrane properties in ageing as well as on introduction of ionophore into the membrane.

[Inhibition of Na+, K+-ATPase activity by sodium channel blockers]. / Ugnetenie aktivnosti Na+, K+-ATFazy blokatorami natrievykh kanalov.

Blocking agent of sodium channels in membranes of epithelial cells amiloride and triamterene as well as tetrodotoxin, which blocked sodium channels in electroexcitable membranes, were found to be effective inhibitors of Na, K-ATPase. A similarity between sodium sites of sodium channels and that of Na, K-ATPase is considered.

[Sodium and chlorine reabsorption system in the kidney of fetal and neonatal rats]. / Sostoianie sistemy reabsorbtsii natriia i khlora v pochke plodov i novorozhdennykh krysiat.

It has been demonstrated that already to the end of embryonic period, foetal rats have rather developed kidney system which is sensitive to one of the most effective diuretics--furosemide (lasix), an inhibitor of chloride channels. Investigation of the activity of transport ATPases revealed the developed system of sodium transport in the kidney of foetal rats.

[Protein level and Na,K-ATPase activity of rat kidney tissues following cis-platin administration]. / Soderzhanie belka i aktivnost' Na,K-ATFazy v tkaniakh pochki krys pri deistvii tsis-platiny.

Concentrations of protein and electrolytes as well as activity of Na,K-ATPase were studied in renal tissue of rats within 5 days after cisplatinum administration (5 mg/kg of body mass, intraperitoneally). There were a significant reduction in the ATPase activity and an increase in water content and sodium concentration in renal cortex tissue, while K+, Ca2+ and Mg2+ were unaltered. At the same time, concentration of electrolytes did not shift in blood serum and muscle tissue. After intraperitoneal administration of choline chloride at a dose of 290 mg/kg of body mass within 40 min before the cisplatinum treatment less distinct alterations were observed in the urea content and in the Na,K-ATPase activity.

[Effect of adrenalectomy on the enzymatic activity in thin kidney slices and homogenates]. / Vliianie adrenéktomii na aktivnost' fermentov v tonkikh srezakh i gomogenatakh pochki.

A method of "thin slices" was developed for estimation of enzymatic activities in cells, in which relationship between structure elements was maintained and the cells were readily permeable for substrates. Activities of Na, K-ATPase and succinate dehydrogenase were markedly higher in thin slices than in homogenates; activities of choline esterase and lactate dehydrogenase were of the same value in both tissue preparations. As compared with controls, adrenalectomy caused a decrease in Na, K-ATPase activity in the tissue slices, activities of succinate- and lactate dehydrogenases were unaltered and the choline esterase activity was increased. Comparison of the enzymatic activities in homogenates and thin slices indicates that some contradictions in data on the effect of the adrenal cortex hormones on the activity of the enzymes involved in the ion transport porcesses are due mainly to unadequateness of the methods used.

[Adenosine triphosphatase activity in the osmoregulatory organs of vertebrates]. / Aktivnost' adenozintrifosfataz v osmoreguliruiushchikh organakh pozvonochnykh.

Studies have been made on the activity of cation- and anion-stimulated ATPases, as well as succinic dehydrogenase in homogenates and subcellular fractions from osmoregulatory organs of marine (elasmobranch and teleost) and freshwater (teleost) fishes, amphibians, reptiles, birds and mammals. The activity of Na+, K+-ATPase was found to be rather similar in almost all osmoregulatory organs of the species investigated. The highest level of Cl-stimulated ATPase was found in microsomal fraction of the kidneys from birds and mammals. Succinic dehydrogenase activity is significantly higher in the renal tissue of mammals, both in total homogenates and in mitochondrial fraction.

[Characteristics of the disorder in the composition of the internal medium and kidney function of vertebrate animals after cisplatin administration]. / Osobennosti narusheniia sostava vnutrennei sredy i funktsii pochki u nekotorykh pozvonochnykh zhivotnykh posle vvedeniia tsis-platiny.

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.

[Succinate dehydrogenase activity in the mesonephros in the process of development of chick embryos]. / Aktivnost' suktsinatdegidrogenazy v mezonefrose v protsesse razvitiia émbrionov tsypliat.

The activity of succinate dehydrogenase in the mesonephros tissue of chick embryos is rather high on the 6th day of embryonal development and is not subjected to significant changes up to the 17th day. The absence of wide variations in the activity of this enzyme during the period of degeneration of the mesonephros may be due to a parallel decrease in the organ's mass and in the number of its mitochondria.

[The effect of regulatory peptides on water absorption in the large intestine of the frog]. / Vliianie reguliatornykh peptidov na vsasyvanie vody v tolstoi kishke liagushki.

Preparation of isolated large intestine of the frog was filled with Ringer's solution diluted with distilled water (1:5) and was placed into the glass with normal Ringer's solution. The preparation was weighed within every 30 min and the osmotic permeability was determined for water of the mucous and serous layers of the intestine. Then one of the peptides was added to Ringer's solution and the experiment continued. It is stated that bombesin, neurotensin, encephalins, substance P, somatostatin, pituitrin are able to change liquid absorption from the large intestine cavity when the concentration of Ringer's solution in the cavity and from its serous surface is the same. Bombesin and neurotensin inhibited while encephalins stimulated liquid absorption and these effects depended on the transport of ions. Liquid absorption by the osmotic gradient decreased using bombesin, substance P and increased using somatostatin. More complex peptide-peptide relations are observed if using pituitrin and other peptides. cAMP is shown to participate in bombesin effects.

[Inhibition of cholinesterase activity in the brain of rats by phosphoorganic inhibitors with different degrees of hydrophobia]. / Ugnetenie kholinésterazoi aktivnosti v mozga krys fosfororganicheskimi ingibitorami s razlichnoi stepen'iu gidrofobnosti

The activity of cholinesterase in different areas of the rat brain was studied as affected by two organophosphophorous inhibitors of the enzyme from the group of O-alkyl-S-hexylthiophosphonates, GA-89 and GA-95. Hydrophobity of GA-95 is two order higher than that of GA-89. Under the effect of GA-89 inhibition of cholinesterase in the brain is considerably higher than in blood, under the effect of GA-95 an inverse relation is observed. When both compounds are administered, the activity of cholinesterase in the cerebral cortex is most inhibited.

Protective effect of antiinflammatory corticosteroid triamcinolone in cisplatin nephrotoxicity.

The corticosteroid, triamcinolone, was examined as a potential antagonist for the nephrotoxicity of cisplatin in female Wistar rats. The changes in renal function and renal morphology were assessed on the 3rd day after administration of cisplatin (7.5 mg/kg BW) and in animals given triamcinolone retard (4 mg/kg BW) 6 h before administration of cisplatin. Pretreatment with triamcinolone resulted in much less severe changes in renal function after cisplatin administration (serum urea: triamcinolone plus cisplatin 14.29 +/- 1.90 mg/l, cisplatin alone 21.60 +/- 2.34 mg/l, p < 0.05, control 2.78 +/- 0.19 mg/l, serum creatinine: triamcinolone plus cisplatin 0.21 +/- 0.02 mg/l, cisplatin alone 0.30 +/- 0.02 mg/l, p < 0.05, control 0.06 +/- 0.01 mg/l). In contrast to cisplatin-treated animals in triamcinolone-pretreated rats alterations of water content were found neither in renal cortex (triamcinolone plus cisplatin 3.39 +/- 0.16 g/g dry weight, cisplatin alone 4.07 +/- 0.07 g/g dry weight, control 3.07 +/- 0.07 g/g dry weight) nor in outer medulla (triamcinolone plus cisplatin 4.20 +/- 0.22 g/g dry weight, cisplatin alone 4.98 +/- 0.21 g/g dry weight, control 3.84 +/- 0.11 g/g dry weight) compared to control. The structure of the kidney following cisplatin administration demonstrated extensive lesions of S3 segments of the proximal tubule. The changes in proximal convoluted tubules were widespread and ranged from the decrease of the amount of microvilli to loss of brush border or even to cell death. In triamcinolone-pretreated rats the structure of the cortex appeared to be virtually normal and tissue of medulla was only slightly damaged.

[Mechanism of activation of acetylcholinesterase in brain tissue homogenates by detergents]. / Mekhanizm aktivatsii detergentami atsetilkhinestera3y V gomogenatakh golovnogo mozga.

The mechanisms of activation of acetylcholinesterase (AChE) in the homogenates of rat and frog forebrains and medullae oblongatae under effects of non--ionic detergents (Triton X-100 and Tw-en 80) were studied. Titration of the active centers of enzyme by the highly selective phosphoorganic inhibitor HD-42 showed that the inhibitor-induced activation is due to the appearance of previously masked active sites of the enzyme. Activation of AChE in the homogenates of rat brain medulla oblongata was caused by lysis of the structural elements of nervous tissue which were not destroyed by homogenization. Another mechanism of AChE activation by the detergents (frog brain homogenate) is the destruction of the vesicular membrane structures present in the homogenate with AChE centers located on the inner surface of the vesicles.

Does the gradual hydroosmotic response to antidiuretic hormone depend on intracellular cAMP accumulation or on the formation of intramembrane particle aggregates?

In experiments on frog urinary bladder the mechanisms behind the gradual development of a hydroosmotic reaction to antidiuretic hormone (ADH) were investigated. It was suggested that the velocity of hydroosmotic reaction may be limited by (a) formation and insertion of particle aggregates into the apical membrane or (b) by velocity of cAMP formation. The urinary bladders were exposed to 23 nM ADH for different times (from 1 to 20 min) and water flow was measured over a period of 40 min. It was found that the value of the full hydroosmotic response increased progressively with the time of exposure to the hormone; however, the enhancement of water flow was equal during each time interval before reaching the reaction maximum. A direct correlation between the value of ADH-stimulated water flow, cAMP content in bladder tissue and frequency of particle aggregates in the granular cell apical membrane was observed. The content of cAMP in ADH-treated bladders was higher by 80% in the absence than in the presence of an osmotic gradient. Pretreatment of urinary bladders with 50 microM cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, significantly accelerated the development of the hydroosmotic reaction and increased the magnitude of water flow in comparison with the effect of ADH only. No changes in cyclic AMP phosphodiesterase activity were found in the urinary bladder homogenates under the action of ADH, so it seems likely that accumulation of cAMP depends only on the increase of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)