[COMBINATION OF TAURINE WITH ZINC DIASPARTATE FOR CORRECTION OF METABOLISM DISTURBANSES IN NEPHRONS AND RENAL FUNCTION IN RATS WITH CONTRAST-INDUCED NEPHROPATHY].

The nephroprotective properties of a combination of taurine with zinc diaspartate (taucin) in rats with contrast-induced nephropathy have been estimated. It is established that the combination of taurine with zinc diaspartate (20 and 1 g/mol, respectively, ingested in doses 250 and 500 mg/kg in the stomach during 14 days) produces a dose-dependent nephroprotective action on rats with contrast-induced (sodium and meglumin amidotrizoates, 800 mg/kg/day intraperitoneally, 14 days) nephropathy.

[Therapeutic effect of acetylcysteine on rats with gentamicin-induced nephropathy].

Gentamicin (60 mg/kg, i.p., once per day for 10 days) produces a nephrotoxic effect in rats, which is manifesting by the epithelium necrosis of proximal convoluted tubules (especially of cortical nephrons), decreasing creatinine clearance, and increasing protein in the urine. Acetylcysteine (40 mg/kg, i.p., once per day for 10 days) significantly decreases manifestations of the gentamicin nephrotoxicity. Acetylcysteine administration leads to the appearance of normal tubules (absent in rats treated by gentamicin), decreases the number of necrotized proximal convoluted tubules of cortical nephrons and reduces their internal diameter, and increases the height of paving epitheliocytes. The content of detrite in tubules of juxtamedullar nephrons decreases, while the activity of alkaline phosphatase in proximal convoluted tubules of cortical and juxtamedullar nephrons and the activity of lactatedehydrogenase in cortical nephrons increases.

[Comparative analysis of the role of individual peculiarities of kidney structure in predisposition to the nephrotoxicity of gentamicin in intact and hydronephrotic rabbits].

Comparative analysis of relationships between individual peculiarities of the structure of nephrons in intact and hydronephrotic right rabbit kidneys, on one hand, and the degree of expression of nephrotoxicity of gentamicin with respect to the only intact and as well hydronephrotic left kidney, on the other hand, was undertaken. Damage of the kidney by this antibiotic is more expressed in rabbits with smaller diameter of distal convoluted tubules of nephrons and smaller size of the cells lining their lumen. These peculiarities of the structure of nephrons lead to predisposition to the gentamicin-induced nephropathy in intact rabbits to a higher degree than in animals with hydronephrosis. The method of predicting individual predisposition to gentamicin-induced nephropathy has been patented (No. 7722 of 13.10.2005).

[Individual activity of renal enzymes in the susceptibility of hydronephrotic rabbits to aminoglycoside (gentamicin) nephrotoxicity].

A correlation between the individual features of the activity of renal enzymes and the expression of aminoglycoside (gentamicin) induced nephrotoxicity is established in hydronephrotic rabbits. The level of gentamicin-induced damage of the kidney is more significant in rabbits with initially (prior to gentamicin administration) increased activity of lactate dehydrogenase, decreased activity of succinate dehydrogenase and acid phosphatase, and low content of ribonucleoproteins.

Role of individual structural features of rabbit kidneys in the predisposition to gentamicin nephrotoxicity.

A relationship between congenital features in the structure of rabbit kidneys and sensitivity to gentamicin nephrotoxicity was revealed. Gentamicin nephrotoxicity is more pronounced in rabbits with lower diameter of nephron convoluted tubules and with smaller cells lining their lumen.

[The role of liver antioxidant system in predisposition of rats to hepatotoxic effect of ethanol]. / Rol' antioksidantnoi sistemy pecheni v predraspolozhennosti krys k gepatotoksicheskomu deistviiu étanola.

A new methodological approach capable of revealing factors responsible for the susceptibility of rat liver to ethanol hepatotoxicity has been developed. Using the correlation, dispersion, iteration, multifactor regression, and canonical analyses, a relation was established between the initial state of the liver antioxidant system and the character and degree of the subsequent ethanol-induced damage. In particular, it was found that intact animals with initially low level of reduced glutathione and retinols in the liver, as well as those with enzymopathy of cytosol HDNB-glutathione-8-transferase, are more susceptible to the ethanol liver damage.

LPO and ethanol biotransformation systems in the liver as markers of predisposition to ethanol hepatotoxicity.

An original experimental model for detecting organ-specific markers of predisposition to ethanol hepatotoxicity is proposed. A relationship between congenital activity of LPO processes in rat liver (before ethanol intoxication) and the type and severity of ethanol-induced damage to the liver was demonstrated using methods of mathematical modeling. It was proven that intact rats with genetically high MDA levels in the liver and more active systems of MDA generation in ascorbate- and NADPH-dependent reactions are prone to ethanol-induced damage to the liver.

Inhibition of enzymes of drug metabolism in rat liver by ultrasound and correction by heparin.

After 6 days following the local effect (during operation) of ultrasound (2 Wt/cm2, 1 min) the microsomal fraction showed decreased total content of cytochromes P-450 (P-450), rate of NADPH oxidation, activity of NADPH-cytochrome P450 reductase and P450 IIE1 (aniline as substrate) by 40, 28, 16 and 42 %, respectively. In addition, after 12 days the activities of P450 IIIA1 (ethylmorphine as substrate) and cytosolic sulphobromophthalein glutathione transferase (SBPh-GT) were decreased by 59 and 26 %. The administration of heparin (intramuscularly, 250 ED/kg, in a day, 3 and 6 times) exerted a normalizing effect. The P450 concentration, NADPH oxidation rate and P450 IIB1 activity (amidopyrine as substrate), IIE1 and IIIA1, SBPh-GT and 1-chloro-2,4-dinitrobenzene-GT in microsomes and cytosol exceeded the corresponding values in untreated animals by 31, 40, 68, 224, 68, 42, 24 and 36 %. The administration of heparin to control animals (intramuscularly, 250 and 500 mg/kg, in a day, 5 times) essentially unaffected both the monooxygenase, glucuro- and glutathione-conjugating systems and the elimination of antipyrine (substrate of preferably P-450 IA2) and SBPh (substrate of GT) from rat blood plasma. The experimental results provide evidence for a possible role of endogenous heparin in maintaing the optimal level of the activities of the enzyme systems of xenobiotics microsomal oxidation and conjugation in liver injury. One of the most important functions of the liver is its ability to execute biotransformation of a wide range of xenobiotics and some endogenous substances [1]. The activities of the enzyme systems catalyzing these reactions are under a sophisticated regulatory control. Among the natural factors capable of changing the function of enzymes involved in the xenobiotic biotransformation are vitamins [2], phospholipids [3], hormones [4] and many others. We studied the effect of heparin on the activities of the monooxygenase, glucuro- and glutathione transferase systems of the intact and ultrasound-treated rat liver. The significance of this study consists in the elucidation of a putative participation of heparin in the control of the activities of the enzyme system of xenobiotic biotransformation in the intact liver and under membranous pathology of the organ.

[The action of Essentiale and its combination with cordiamine and vitamin E on the processes of xenobiotic biotransformation and lipid peroxidation and on liver structure in rats with cholestasis]. / Deistvie essentsiale, ego kombinatsii s kordiaminom i vitaminom E na protsessy biotransformatsii ksenobiotikov, perekisnogo okisleniia lipidov i struktury pecheni krys s kholestazom.

Intensive regeneration of cholangia and cholangioles, fibrosis, microglobular cirrhosis, vacuolar and granular dystrophy, and necrosis of hepatocytes were found in the liver of rats 36 days after ligation of the common bile duct. Lipid peroxidation was activated, the activity of the mono-oxidase system was inhibited in maintained function of glucuro- and glutathione transferase. Essentiale (per os in starch mucilage, 1 ml/kg. for 35 days) increased the activity of cytosol glutathione-S-transferase and normalized the decreased blood plasma antioxidant activity. Combination of essentiale with cordiamin (nikethamide) and viatmin E (50 mg/kg for 35 days) considerably activated the mono-oxigenase, glucoro- and glutathione transferase systems of the liver: the free-radical processes became less intense. The structure of the liver improves insignificantly in both methods of treatment.

[The effect of nicotinamide, methionine and alpha-tocopherol on the liver conjugating and mono-oxygenase systems and on lipid peroxidation in hepatosis-hepatitis in rats]. / Vliianie nikotinamida, metionina i al'fa-tokoferola na aktivnost' kon''iugiruiushchei i monooksigenaznoi sistem pecheni i perekisnoe okislenie lipidov pri gepatozogepatite u krys.

Four days after a single intragastric injection of CCl4 (5 mg/kg as a 50% oil solution) increased intensity of a chemoluminescence "quick flush" in the hepatic microsomes and blood serum, as well as hepatocyte cytolysis (increased ALT activity) and decreased rate of antipyrine elimination from the blood were recorded in rats. The content of cytochromes P-450 and b5 activity of NADH-cytochrome b5 reductase and cytosol glutathione transferase in the hepatic microsomal fractions reduced in this case. Administration of methionine (200 mg/kg) and its combination with nicotinamide (60 mg/kg) without and, particularly, with additional prescription of vitamin E (150 mg/kg) produced a marked antioxidant and enzyme-normalizing effects in the rats.

[The effect of heparin on the activity of the mono-oxygenase glucuronyl- and glutathione transferase systems in ultrasonic damage to the rat liver]. / Vliianie geparina na aktivnost' monooksigenaznoi gliukuro- i glutationtransferaznoi sistem pri ul'trazvukovom povrezhdenii pecheni krys.

Six days after local exposure of the rat liver (during operation) to ultrasound (2 W/cm2, 1 min), the cytochrome P-450 content in the microsomal fraction reduced, and the rate of NADPH oxidation, the NADPH cytochrome P-450 reductase activity, ethylmorphine demethylation and aniline hydroxylation decreased in 12 days the activity of NADPH-cytochrome b5 reductase and cytosol sulfobromophthalein-glutathione-S-transferase also reduced. Heparin administration (250 U/kg i.m. every other day 3 and 6 times) had an enzyme-activating effect (particularly in the late-term restoration period) in animals which had been exposed to ultrasound.

[Effect of long-term administration of undevit and its combination with cordiamine on hydroxylation, glucuronidation and glutathione conjugation systems and lipid peroxidation in rat liver]. / Vliianie dlitelnogo vvedeniia undevita i ego kombinatsii s kordiaminomna gidroksiliruiushchuiu, gliukuro-, glutationkoníugiruiushchuiu sistemy i perekisnoe okislenie lipidov pecheni intaktnykh krys.

Increase of N-demethylase and antioxidant activities and decrease of amount of hydroperoxides were observed in liver of rats after intragastric administration of Undevit (1/8 dragee/rats/day, 5 times a week during 2 months). Combination of Undevit with Cordiamin (5 mg/rat/day) resulted in augmentation of cytochromes P-450 and b5 content and activities of their reductases, velocity of amidopyrine and ethylmorphine N-demethylation and oxidation of HADPH. Activities of UDP-glucuronyltransferase, glutathionetransferase and hydrophobity of microsomal membranes were also increased. Antioxidant activity was increased and amount of hydroperoxides in liver microsomes and homogenates and in plasma was decreased in greater degree after administration of combination two compounds than after administration of Undevit alone.