Effect of ethanol on the DNA-polymerase activity in the liver subcellular fractions of adult and old rats

The effect of 5% ethanol on DNA polymerase activity in nuclei, mitochondria, microsomes and cytosol of intact and regenerating liver of adult and old rats has been studied. No changes in DNA polymerase activity were detected in subcellular fractions of adult rat liver. On the contrary, the increased activity of intact liver nuclei and decreased activity of regenerating liver microsomes was observed with ageing. These age-dependent peculiarities of DNA polymerase activity in response to 5% ethanol may be related to changes in the enzyme molecules or microenvironment associated with ageing.     

DNA-polymerase activity of the liver of adult and old rats

The DNA-polymerase activity was determined in the cytosol of the intact and regenerating liver of adult and old rats under conditions of free passage of enzymes from nuclei and mitochondria. The DNA-polymerase activity of the intact liver is significantly increased in adult rats. The regeneration results in about 2-fold and 10-fold increase of the activity in the liver of adult and old rats, respectively. As a result, the DNA-polymerase activity in the regenerating liver of old rats significantly increased as compared to that of adult rats. The revealed age-related changes in the DNA-polymerase activity of the liver do not correlate with the decrease in the replication rate in the process of aging.     

Effect of caloric restricted diet on the liver microsomal monooxygenase system in rats of various ages

Dietary restriction is the only known experimental method to extend lifespan in mammals, but the mechanisms of this phenomenon are still unknown. It is determined that the keeping of animals on the calorie restricted diet results in essential changes of a drug-metabolizing enzymes contents, that is also confirmed by the change of response of the enzyme system to thyroxine action. As a whole, the results obtained will be coordinated with the point of view, according to which the action mechanisms of the dietary restriction consist in considerable change of a wide spectrum of biochemical processes, including the change of the level of monooxygenase system functioning.     

Effect of praseodymium chloride on liver microsomal enzymes of rats

A single i.v. dose (5 mg/kg) of a light lanthanon, praseodymium, prolonged the duration of hexobarbital-induced sleep and zoxazolamine-induced paralysis, as well as it modified pharmacokinetic parameters of hexobarbital and zoxazolamine, in rats. Half-lives (t1/2) and area under the curve (AUC) were increased, while elimination coefficient (beta) and clearance (Cl) were decreased. However, in daily doses of 1 mg/kg i.p. for 15 days, praseodymium did not alter pharmacological effects and pharmacokinetic parameters. The in vitro hydroxylation of hexobarbital and zoxazolamine by liver microsomes was inhibited when the animals were treated previously with a single i.v. dose (5 mg/kg) of praseodymium chloride. In these animals, the amount of cytochromes P-450 and b5 were reduced significantly, whereas that of NADPH-cytochrome c reductase remained unchanged. The pretreatment of animals with phenobarbital normalized the microsomal enzyme impairment caused by praseodymium.     

Effect of contraceptive treatment on thymic glucocorticoid receptors and hepatic microsomal enzyme system of adult rats.

Contraceptive steroid treatment accounted for about a 30 per cent decrease in the number of thymic glucocorticoid receptors of adult rats. Neonatal allylestrenol treatment had no influence on that treatment. The activity of the hepatic microsomal (PSMO) enzyme system was not changed by the contraceptive treatment. It appears that contraceptive treatment may account for overlaps on receptors in adulthood.     

Effect of sodium sulfate on the microsomal oxidation system in the liver and the morphological status of the internal organs of the white rat

The morphological state of the internal organs as well the changes of microsomal oxidation in liver of white rats exposed to the action of sodium sulfate in doses 200 and 600 mg per 100 g of body weight have been studied. The sodium sulfate in dose 600 mg per 100 g of body weight has been found to decrease the cytochrome P450 content, increase its inactivation rate and have an injurious effect on the membranes of hepatocytes. Sodium sulfate administration through the gastroenteric tract causes the destructive and pathological histochemical changes in liver, stomach, duodenum and small intestine. The alternative changes are expressed most of all in duodenum and small intestine.     

The antioxidative activity of drugs in the liver microsomal system of rats]

The antioxidative properties of drugs--diethylcarbamazine citrate--DECC, dipyridamole-DP, levamisole and labinzarit--have been investigated in various microsomal lipid peroxidation (LPO) models: NADPH-, ascorbate- and CCl4-dependent. The most strong antioxidant of direct action turned out to be DP, DECC exhibited the antioxidative properties as a result of metabolic activity in monooxygenases system of rat liver microsomes. Levamisole and labinzarit turned out to be weak antioxidants. The control of microsomal membrane stability against Fe(2+)-ADP, NADPH-induced LPO, after being isolated from rat liver after the action of CCl4 without and with DECC, showed that DECC protected microsomal membranes from CCl4 in vivo and they remained stable against LPO in vitro.     

Oxidative stress, microsomal and peroxisomal fatty acid oxidation in the liver of rats treated with acetone

Parameters of oxidative stress, microsomal cytochrome P450 activity and peroxisomal fatty acid oxidation were studied in liver of rats following acetone (1% v/v) consumption for 7 days. Acetone treatment increased the activity of catalase and decreased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GTPx), but did not significantly modify the liver content of malondialdehyde (MDA) and reduced glutathione. Also, acetone increased the total content of cytochrome P450, the microsomal lauric acid hydroxylation, aminopyrine N-demethylation and the peroxisomal beta-oxidation of palmitoyl CoA. These effects were similar to those found previously in starved and ethanol-treated rats, supporting the hypothesis that ketone bodies would be the common inducer of microsomal and peroxisomal fatty acid oxidation in these metabolic states.     

The microsomal oxidation system of the liver in the aging of animals with various specific lifespans

Experiments, carried out on adult and old animals with different specific lifespan (rat, guinea pig, rabbit, and dog), revealed age-related changes in content and activity of liver microsomal oxidation enzymes (cytochrome P-450, b5, aminopyrine demethylase, aniline hydroxylase). The changes become more pronounced with age. This allows to classify these species as chronobiological ones. A negative correlation between the specific lifespan and the level of decrease in activity of aminopyridine demethylase, an integral index of electron transport rate in microsomal chain, in aged animals was established.     

Effect of thiourea on microsomal oxidation of alcohols and associated microsomal functions.

Thiourea and diethylthiourea, two compounds which react with hydroxyl radicals, inhibited NADPH-dependent microsomal oxidation of ethanol and 1-butanol. Inhibition by both compounds was more effective in the presence of the catalase inhibitor, azide. Inhibition by thiourea was noncompetitive with respect to ethanol in the absence of azide but was competitive in the presence of azide. Urea, a compound which does not react with hydroxyl radicals or H2O2, was without effect. Thiourea had no effect on NADH- and NADH-cytochrome c reductase, NADPH oxidase, and NADH- and NADPH-dependent oxygen uptake. Thiourea inhibited the activities of aniline hydroxylase and aminopyrine demethylase. Thiourea, but no other hydroxyl radical scavengers, e.g., dimethyl sulfoxide, mannitol, and benzoate, reacted directly with H202 and decreased H2O2 accumulation in the presence of azide. Therefore the actions of thiourea are complex because it can react with both hydroxyl radicals and H2O2. Differences between the actions of thiourea and those previously reported for dimethyl sulfoxide, mannitol, and benzoate, e.g., effects on drug metabolism, effectiveness of inhibition in the absence of azide, or kinetics of the inhibition, probably reflect the fact that thiourea reacts directly with H2O2 whereas the other agents do not. The current results remain consistent with the concept that microsomal oxidation of alcohols involves interactions of the alcohols with hydroxyl radicals generated from microsomal electron transfer.     

Effect of nonsteroidal anti-inflammatory drugs on the microsomal monooxygenase system of rat liver

The effect of acetylsalicylic acid, ibuprofen, indomethacin, ketoprofen, naproxen, phenylbutazone, and salicylic acid on the microsomal oxidative drug metabolism of rat liver was studied. Pretreatment of the rats with pharmacologic doses of acetylsalicylic acid, indomethacin, and ketoprofen decreased both the demethylase and hydroxylase activities of rat liver microsomes. These effects were paralleled by decreases in microsomal cytochrome P-450 content. The rate of the microsomal reactions was increased after pretreatment with ibuprofen and naproxen but only the former increased the concentration of cytochrome P-450. Phenylbutazone and salicylic acid had no in vivo effect on the hepatic monooxygenase. The addition of 1 mM of ibuprofen, indomethacin, ketoprofen, naproxen, and phenylbutazone to rat liver microsomes inhibit both the aminopyrine N-demethylase and p-nitro-anisole O-demethylase activities. The extent of the inhibition varied between 21 and 73% of the control incubation. Indomethacin, naproxen, and phenylbutazone also decreased the aniline hydroxylase activity to roughly 60% of the control value. Acetylsalicylic acid and salicylic acid had no in vitro effect on the microsomal monooxygenase. The nonsteroidal anti-inflammatory drugs produced a reverse type I binding spectrum with oxidized cytochrome P-450; indomethacin and phenylbutazone were the strongest ligands. There is no correlation between the effect of addition of nonsteroidal anti-inflammatory drugs to the hepatic microsomal homogenate and their in vivo effect on the monooxygenase activity.     

Survival of Pacinian corpuscles after denervation in adult rats

Summary The ultrastructure of Pacinian corpuscles located on the crural interosseous membrane was studied in adult rats 6 h to 10 months after transection of the right sciatic nerve. Axon terminals degenerated one day after transection and were engulfed and resorbed by cells of the inner core within one week. The axial space left after removal of the axonal debris was closed by the lamellae of the inner core. The main structural features of the inner core and capsule remained preserved after denervation throughout the period of study. The denervated inner cores, however, became atrophic 10 months after neurotomy, their mean diameter being reduced by 17.5% compared with that of contralateral control corpuscles. The number of capsular lamellae was unaltered, and perineurial pathways of the peripheral nerve stump remained preserved. Schwann cells proliferated and formed Büngner bands during the first month after denervation, but retracted their processes and became atrophic at later stages after neurotomy.Survival of Pacinian corpuscles after long-term denervation in adult rats is in contrast to their rapid degeneration within several days after nerve section in neonates.     

The effect of hypoxia and of subsequent baro-oxygenation on the function of the microsomal oxidation system in the rat liver]

The increase of cytochrome P-450 by 34% and its catalytic activity with substrate amidopyrine by 57% as compared with control has been shown under hypoxia (0.029 MPa, 1 h). Hyperoxia (0.2 MPa, 1 h) increases the metabolism of amidopyrine by 148%, benzo[a]pyrene by 158% and aniline by 114% and consecutive affection of hypoxia and hyperoxia--by 247, 45 and 138% correspondingly at fixed cytochrome P-450 amount in both series. The amount of diene conjugates and Schiff's bases under hypoxia increases by 40 and 69% correspondingly, the activity of SOD and catalase decreases by 25 and 23%. The activity of hyperoxia raises the diene conjugate content by 19% at all this SOD activity increases by 95%. Consecutive affection of hypoxia and hyperoxia increases the level of diene conjugates and Schiff's bases by 26 and 23% correspondingly, without changing SOD and catalase activity. The relative microsomal viscosity of lipid layer and zones of enzyme-lipid contacts decreased by 20 and 24% under hypoxia, but under hyperoxia and consecutive affection and hypoxia and hyperoxia it increases by 29-28% and 56-40% correspondingly.