[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.

[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.

[The effect of methotrexate on phenobarbital induction of monooxygenases and UDP-glucuronyltransferases in rat liver]. / Vliianie metotreksata na fenobarbitalovuiu induktsiiu monoksigenaz i UDF-gliukuronoziltransferazy pecheni krys.

Methotrexate (N10-methyl-4-amino-4-deoxyfolic acid), administered to rats subcutaneously at a dose of 0.25 mg/kg within 14 days, was found to decrease content of microsomal protein in liver tissue and content of cytochromes P-450 and b5 as well as the drug decreased activity of amidopyrine- and ethylmorphine-N-demethylases, aniline-p-hydroxylase, UDP-glucuronosyltransferase and urinary excretion of glucuronides by 21%, 60%, 39%, 33%, 53%, 21%, 41% and 28%, respectively. Phenobarbital, administered subcutaneously at a dose of 60 mg/kg within 14 days, elevated the parameters by 28%, 187%, 63%, 163%, 162%, 100%, 95% and 60%, respectively. The effect of phenobarbital in combination with methotrexate was decreased by 77%, 49%, 55%, 52%, 43%, 42% and 22%, respectively.

[A comparative study of the effects of nicotinamide and diethylnicotinamid on hepatic monooxygenase, glucuronyl and glutathione conjugating systems]. / Sravnitel'noe izuchenie vliianiia nikotinamida i diétilnikotinamida na monooksigenaznuiu, gliukuronil- i glutationkon"iugiruiushchuiu sistemy pecheni.

The nicotinamide administration to rats (50 mg/kg, subcutaneously, over 5 days) increased the concentration of liver cytochrome b5, the activities of cytosol and microsomal glutathione S-transferase, UDP-glucuronosyltransferase and urinary excretion of bound glucuronic acid by 26.7, 33.1, 33.3, 53.0 and 31.0%, respectively. The chloral hydrate-induced sleep time in mice was reduced by 65%. Under similar experimental conditions the administration of equimolar amounts of diethylamide of nicotinic acid (75 mg/kg) exerted a more pronounced enzyme-stimulating effect. The cytochrome P-450 concentration, the activities of cytosol and microsomal glutathione S-transferase, UDP-glucuronosyltransferase as well as the sulphobromophthalein elimination from blood plasma and urinary excretion of bound glucuronic acid were increased by 37.0, 33.1, 54.6, 80.5, 24.5 and 49.0%, whereas the chloral hydrate-induced sleep time decreased by 75%. The nicotinamide and diethylamide of nicotinic acid stimulating effects on xenobiotic biotransformation in rat liver are assumed to be due to enhanced NADPH, glutathione and UDP-glucuronic acid biosynthesis as well as their antioxidant properties.

[Changes in UDP-glucuronosyl-, glutathione-S-transferase and lipid peroxidation in rat liver microsomes during gamma-irradiation and protective effect of alpha-tocopherol]. / Izmenenie aktivnosti UDP-gliukuronozil-, gliutation-S-transferaz i perewkisnogo okisleniia lipidov mikrosom pecheni krys pri gamma-obluchenii i zashchitnoe deistvie alpha-tokoferola.

Stimulation of lipid peroxidation, accompanied by a decrease in activity of UDP-glucuronyl- and glutathione-S-transferases, was observed in rat liver microsomes within one day after gamma-irradiation. Maximal alteration of the patterns studied was detected within 5 days. Preadministration of alpha-tocopherol, within 14 days at a dose of 200 mg/kg of body mass, prevented distinctly the impairing effect of irradiation.

[The effect of diethylnicotinamide (cordiamine) on the activity of the hydroxylating and glucuronyl-conjugating systems in humans]. / Vliianie diétilnikotinamida (kordiamina) na aktivnost' gidroksiliruiushchei i gliukuronilkon''iugiruiushchei sistem u liudei.

Administration of diethylnicotinamide (250 mg orally three times for 8 days) to healthy subjects increased antipyrine (AP) elimination from the saliva by 23% and decreased its half-life by 26%. The excretion in the urine of the products of AP hydroxylation 3-carboxymethylantipyrine and nor-antipyrine as well as glucuronides 3-hydroxymethylantipyrine increased. A positive correlation between the dynamics of the excretion of antipyrine metabolites and glucuronic acid was observed. The elimination from blood of bilirubin glucuronides increased. Diethylnicotinamide in therapeutic doses is supposed to stimulate the processes of hydroxylation and glucuronyl conjugation in humans.

[The effect of folic acid and methotrexate on the activity of the glucuronyl- and glutathione-conjugating systems of the liver in rats]. / Vliianie folievoi kisloty i metotreksata na aktivnost' gliukuronil- i glutationkon''giruiushchikh sistem pecheni krys.

Administration to intact male rats of folic acid (25 mg/kg intragastrically for 14 days) was shown to increase and that of methotrexate (0.5 mg/kg subcutaneously) for 14 days) to decrease the activities of the rat liver uridine-diphosphate-glucuronosyl- and glutathione-S-transferases.

[The role of lipid peroxidation in the pathogenesis of viral hepatitis]. / K voprosu o roli perekisnogo okisleniia lipidov v patogeneze virusnogo gepatita.

Content of blood bilirubin was increased 3.3-11.4-fold as well as 4-10-activation of alanine aminotransferase and glutathione S-transferase was found in patients with virus hepatitis as compared with normal state. At the same time, lipid peroxidation was activated 1.9-3.5-fold in blood plasma as shown by means of chemoluminescence procedure, while the antioxidative activity was decreased 2.2-2.3-fold.

[Effect of nicotinic acid, nicotinamide and its combination with ziksorin and phenobarbital on the UDP glucuronyl transferase activity of the hepatic endoplasmic reticulum in the rat]. / Vliianie nikotinovoi kisloty, nikotinamida i ego kombinatsii s ziksorinom i fenobarbitalom na aktivnost' UDF-gliukuroniltransferazy éndoplazmaticheskogo retikuluma pecheni krys.

Nicotinic acid and nicotinamide (100 mg/kg) increase the activity of the rat liver microsomal uridine diphosphate-glucuronyltransferase by 55 and 73.8%. Administration of nicotinamide in combination with ziksorin or phenobarbital enhanced the enzyme-inducing effects of the latter.

[Effect of nicotinamide on lipid peroxidation]. / Vliianie nikotinamida na protsessy perekisnogo okisleniia lipidov.

Nicotinamide (10-100 mM) caused a decrease in total "fast" flash of chemoluminescence, in rates of NADPH- and ascorbate dependent lipid peroxidation in microsomal fraction of rat liver tissue. Content of cytochrome P-450 (carbonyl complex) as well as rates of amidopyrine N-demethylation and aniline p-hydroxylation were also decreased in microsomal fraction. At the same time, inhibition of chemoluminescence was found after addition of 50, 100 mM nicotinamide to blood plasma or to solution of oxidized oleic acid. With an increase in nicotinamide concentration its inhibitory effect on lipid peroxidation was more distinct.

[Effect of folic acid on the activity of monooxygenase system, UDP-glucuronyl- and glutathione-S-transferase in the normal and regenerating rat liver]. / Vliianie folievoi kisloty na aktivnost' monooksigenaznoi sistemy, UDF-gliukuronil- i glutation-S-transferaz normal'noi i regeneriruiushchei pecheni krys.

After administration into rats of folic acid at a dose of 25 mg/kg within 14 days activities of NADPH-cytochrome P-450 and NADH-cytochrome b5 reductases, content of cytochromes P-450 and b5 as well as the rates of NADPH and NADH oxidation were increased in liver microsomes. The stimulating action of the vitamin was also observed within later periods of liver tissue regeneration during 8 days after partial hepatectomy. Content of cytochrome b5, binding of cytochrome P-450 with aniline, N-demethylation of ethylmorphine as well as activities of UDP-glucuronyl- and glutathione-S-transferases were increased by 23-46% after the treatment as compared with control partially hepatectomized animals. At the period of high mitotic activity of hepatocytes, within 2 days after the operation, the vitamin did not affect the parameters studied.

[Action of substances altering the intracellular cAMP level on the enzymes of the oxidative metabolism of xenobiotics]. / Deistvie veshchestv, izmeniaiushchikh vnutrikletochnyi uroven' tsAMF, na fermenty okislitel'nogo metabolizma ksenobiotikov.

The substances decreasing (insulin subcutaneously 30 U/kg single dose) and increasing (isadrin, theophylline orally 30 mg/kg five times with 12-hour intervals) the intracellular level of cAMP exert varying effects of the activities of mono-oxygenases of the rat liver endoplasmic reticulum. Insulin decreases aniline binding with cytochrome P-450 and the rate of its p-hydroxylation (after 6, 12 hours), the content of cytochrome P-450 and the rate of NADP.H oxidation (after 12 hours), the rate of NAD.H oxidation (after 24 hours). The activity of NADP.H-nitrotetrazolium reductase, content of cytochrome B5, the rate of aniline p-hydroxylation are increased by theophylline, and the rate of NADP.H and NAD.H oxidation and the content of cytochrome P-450 are increased by theophylline and isadrin.

[Effect of folic acid and methotrexate on the function of the hydroxylating system and the cholesterol and phospholipid content in the liver microsomes of rats]. / Vliianie folievoi kisloty i metotreksata na funktsiiu gidroksiliruiushchei sistemy, soderzhanie kholesterina i fosfolipidov v mikrosomakh pecheni krys.

Folic acid and its antivitamin methotrexate exert contrary actions on the activity of monooxygenases of the rat liver endoplasmatic membranes. Under the influence of folic acid (intra-abdominally, 100 mg/kg-6 days, 25 mg/k-14 days) there is a growth in the B5 and P-450 cytochrome content, NADP.H-cytochrome P-450 and NAD.H-cytochrome B5-reductase activity and in the oxidation rate of NADP.H, NAD.H and ethylmorphine N-demethylation. In similar experimental conditions, methotrexate (subcutaneously 0.25 and 1 mg/kg for 6 days, 0.25 mg/kg for 14 days) decreases the rate of NAD.H and NADP.H oxidation and NAD.H-cytochrome B5-reductase activity, the content of cytochromes B5 and P-450 and the binding degree of the latter with ethylmorphine, aniline and their metabolic rate. A decrease of the dose of the agents with a simultaneous increase of the time of administration enhances the vitamin action and reduces that of the antivitamin.