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Biomedical subjects

W Klinger

Publications and source records attributed to W Klinger.

At least 55 records · Page 3Linked to original sources
PubMed1991

Experimental treatment of thioacetamide-induced liver cirrhosis by metenolone acetate. A morphological and biochemical study.

The influence of metenolone acetate (1 mg/kg b.m. orally) on intact and chronically thioacetamide-injured rat liver (experimental liver cirrhosis) was investigated over 14 d. Histological examination revealed nodular transformation of liver structure according to cirrhosis like lesions with hepatocellular and cholangiocellular proliferations. These structural alterations were more serious in the group treated with metenolone compared with the group without metenolone. Metanolone administration to animals with thioacetamide-induced experimental liver cirrhosis led to an increase in liver injury. This treatment seems to promote hepatic preneoplastic lesions induced by thioacetamide reflected by histology and induction of gamma-glutamyltranspeptidase and 7-ethoxycoumarin O-deethylase in injured livers. Metenolone did not interfere directly with the processes of connective tissue synthesis and degradation after thioacetamide pretreatment. Only little changes of the investigated biochemical parameters were seen after metenolone administration to animals with intact liver function: increases in serum cholinesterase and tissue N-acetyl-beta-D-glucosaminidase activity; decreases in N-acetyl-beta-D-glucosaminidase in serum, liver hydroxyproline content and hepatic gamma-glutamyltranspeptidase activity. The observed changes reflect hepatic adaption processes under the influence of metenolone. The results of this study indicate that the risk of anabolic steroids in adjuvant therapy of liver cirrhosis cannot be calculated at present.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1991

The influence of "essential" phospholipids (EPL) on phase-I- and phase-II-reactions and on the glutathione status in the liver of aging rats.

"Essential" phospholipids (EPL; polyene-phosphatidylcholine) were administered orally to aging male rats in doses of 100 and 300 mg/kg b.wt. over 10 weeks. One and 7 days after the last treatment cytochrome P-450 concentration, epoxide hydrolase and glutathione-S-transferases were found to be unchanged, but ethylmorphine N-demethylation, ethoxycoumarin O-deethylation and UDP-glucuronosyltransferase activities were enhanced, as were the concentrations of both reduced and oxidized glutathione, the values being similar to those in young adult rats. These results are discussed in terms of an increase in endoplasmic reticulum membrane fluidity.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1991

Gamma-glutamyltranspeptidase (GGT) in experimental liver cirrhosis induced by thioacetamide: a biochemical and enzymehistochemical study.

Micro- and macronodular experimental cirrhosis-like liver lesion was induced in female rats by administration of 0.03% thioacetamide (TAA) in drinking water for 3 or 6 months. The activity of gamma-glutamyltranspeptidase (GGT) and the distribution pattern of this enzyme within the liver structure were investigated 14 d after withdrawal of TAA in comparison to neonatal and adult normal liver. GGT activity was extremely high at birth. Chronic TAA administration led to a strong increase in hepatic GGT activity in dependence on duration of TAA administration in comparison to adult controls. In accordance to these results we observed by enzyme-histochemistry a small to moderate hepatocellular GGT activity after 3 months of TAA treatment. GGT activity was also demonstrable in epithelia of proliferated ductuli biliferi of single enlarged portal tracts. After 6 months of TAA administration the hepatocellular GGT activity was moderate to strong. It was demonstrable both in parenchymal (preneo-plastic) nodules and in cholangiocellular/cholangioductular proliferates. A GGT activity of mesenchymal cells was not demonstrable. We conclude that the increased hepatic GGT activity after chronic TAA administration can be correlated with the process of development of preneoplastic nodules. A relation between increased GGT activity and the process of cirrhogenesis does not seem to be probable in this animal cirrhosis model.

Animals↗
PubMed1991

The influence of the radiation syndrome on cytochrome P450-dependent monooxygenation in rat liver.

Cytochrome P-450 concentration and the monooxygenation activities of some cytochrome P-450 forms were determined in rat liver in the course of the acute radiation sickness. Ethylmorphine N-demethylation, ethoxycoumarin, ethoxyresorufin, and pentoxyresorufin O-dealkylation were used as indicator reactions. After radiation a distinct decrease in the hepatic biotransformation capacity can be observed, most pronounced at the climax of the radiation syndrome. Phenobarbital treatment (60 mg/kg b. m. at 3 consecutive days each) increases the concentration and the monooxygenase activities of some cytochrome P-450 forms. The degree of this induction effect is not altered at the third day after radiation, whereas at day 7 no significant inducibility can be observed.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1991

Influence of aging, training and acute physical exercise on plasma glutathione and lipid peroxides in man.

In trained (long-distance runners) and untrained volunteers aged 22 to 57 years, basal plasma glutathione (GSH) concentration decreased significantly with increasing age. In most age groups basal GSH concentration of oxidized glutathione (GSSG) and lipid peroxides (LPO) was not influenced either by age or by training. Following acute physical exercise (bicycle ergometric test), which was maximal for each person and thus different in trained and untrained persons, plasma GSH, GSSG, and LPO concentrations were not changed at all in untrained volunteers. In trained persons, however, GSH concentration was significantly decreased by about 30%. Surprisingly, we observed a decrease in plasma LPO content by about 40%. GSSG content was not altered. The comparison with some physical-physiological parameters indicates that the changes in GSH and LPO concentrations depend on the extent of acute physical exercise rather than on previous training. Alterations of GSH and LPO in plasma could be of physiologic significance.

Adult↗
PubMed1991

[The effect of hadacidin, ultraviolet irradiation of blood (UVB) and thiamine on the prenatal development of Uje:WIST rats: correlation with the hepatic activity of gamma-glutamyltranspeptidase (GGT)].

The influence of hadacidin, a model substance for induction of cheilognathouranoschisis in rat fetuses (2,550 mg/kg b.m. at gestation day 12), ultraviolet irradiation (UVB) of blood (1 week before gestation) and thiamine (25 mg/kg b.m. from gestation days 12 to 15) on the prenatal development of rats at the 20th day of gestation was investigated. Using the body mass and the hepatic GGT-activity as parameters. Hadacidin caused a distinct retardation of the fetal somatic development. Partially, the embryotoxic effect was compensated by UVB or thiamine. The combination of both procedures was more effective. There is a good correlation between the maturation grade of fetuses at day 20 of gestation and the hepatic GGT activity.

Animals↗
PubMed1991

Ontogenetic changes in hepatic glutathione system (synthesis, catabolism, export) of male Uje:WIST rats.

The age-courses of concentrations of reduced (GSH) and oxidized (GSSG) glutathione, of GSH synthesizing enzyme activities, of glutathione S-transferase (GST), of GSSG-reductase (GR) and of biliary GSH and GSSG export were measured in livers from male Uje:WIST rats. Additionally, the age-courses of plasma GSH and GSSG concentrations were investigated. The hepatic level of GSH showed a biphasic pattern with a first maximum immediately after birth and a small second peak at the 50th day of life. The GSSG level increased continuously up to day 60 of life. The cytosolic GSH synthesizing enzyme activities showed diverse developmental patterns indicating different regulation principles. The hepatic activity of GR was relatively constant in the different age groups after birth. The GST activity (with o-dinitrobenzene as substrate) was relatively low at birth (about 30% of the maximum measured at day 60 of life). The maximum of GSH plasma level was found at birth. With increasing age a significant decrease in this level was observed. The excretion rate of total GSH (GSH + 2 GSSG) in bile was found to increase about 9-fold between 15 and 105 days of age. The results indicate that changes of hepatic GSH concentration with age are dependent on numerous factors. The balance between synthesis, catabolism and export is important for the maintenance of this level.

Aging↗
PubMed1991

Influence of neonatal and postnatal administration of diethylstilbestrol on hepatic monooxygenase activities and lipid peroxidation in adult rats.

Treatment of adult male and female rats with DES caused a significant reduction of cytochrome P450 concentration, ethylmorphine N-demethylation and ethoxycoumarin O-deethylation. These decreases are not modified by a neonatal treatment with this hormone. In contrast to monooxygenase activities the NADPH-induced lipid peroxidation shows only a tendency to decrease if animals received DES as adults. But a decrease of about 50% is observed after "neonatal plus treatment of adults" with DES. The role of formation of reactive oxygen species characterized by chemiluminescence methods in connection with lipid peroxidation is discussed.

Animals↗
PubMed1990

The hepatic glutathione system--influences of xenobiotics.

The hepatic glutathione (GSH) system and the influences of xenobiotics have been reviewed. Key steps in the regulation of hepatic GSH are GSH biosynthesis, the GSH-peroxidase/reductase cycle, the cystathionine pathway, and the carrier-mediated export processes. Influences of xenobiotics on these different pathways are discussed. Xenobiotics may lead to liver injury after biotransformation to highly reactive electrophilic metabolites (mainly cytochrome P-450 mediated), which easily conjugate with GSH, thus producing GSH depletion. This GSH depletion and probably an additional loss of protein sulfhydryl groups cause a disturbance of the intracellular calcium homeostasis which leads to an irreversible cell injury. The different acinar distribution of cytochromes P-450 and of GSH and GSH-related detoxication pathways points to a greater susceptibility of perivenous hepatocytes to xenobiotic-induced damage. Also, the intracellular compartmentation of GSH is important for the understanding of hepatocellular injury induced by several xenobiotics.

Animals↗
PubMed1990

Influence of acute physical exercise on glutathione and lipid peroxides in blood of rat and man.

In rats physical exercise (30 min running on a treadmill) lowered total glutathione, oxidized glutathione and lipid peroxide concentration in blood. In man (young healthy male volunteers, moderate to excellent physical condition) running (30 min) did not influence these parameters. It is concluded that by normal life and psychophysical vigilance the moderate oxidative stress could be compensated.

Adult↗
PubMed1990

Glutathione levels in liver and brain of newborn rats: investigations of the influence of hypoxia and reoxidation on lipid peroxidation.

1. The levels of reduced glutathione (GSH) in the liver and brain of newborn rats were independent of the birth mechanism (Cesarean section or natural birth). A significant increase of GSH content could be demonstrated 3 h after birth in the liver only. 2. The influence of reversible hypoxia (9 vol. % O2 in the respired air for one hour) on GSH and oxidized glutathione (GSSG) levels and the content of thiobarbituric acid (TBA) reagible products were investigated in the liver and brain of newborn rats in dependence on the duration of reoxygenation. Only small changes were observed in the liver indicating a relative resistance of this organ to hypoxic stress and reoxygenation. Distinct effects were found in the brain, indicating that the glutathione status is altered by increased lipid peroxidation.

Animals↗
PubMed1990

Influence of age, phenobarbital and beta-naphthoflavone on hepatic microsomal lipid peroxidation in rats.

The NADPH-dependent lipid peroxidation is low in liver microsomes of newborns and increases to day 30 of life. Thereafter nearly no changes in lipid peroxidation occur. The relatively high rate of lipid peroxidation in fetal liver microsomes is of interest. The well known inducers of the monooxygenase system phenobarbital and beta-naphthoflavone change lipid peroxidation only in liver microsomes of newborns. Lipid peroxidation is connected with the formation of reactive oxygen species and organic radicals characterized by the chemiluminescence with the amplifiers luminol and lucigenin. Chemiluminescence increases with increasing age depending on the amplifier. Treatment of the animals with phenobarbital causes the most pronounced increase in chemiluminescence of the 10-day-old animals, independent of the amplifier used. beta-naphthoflavone leads to an increase in chemiluminescence in microsomes of all age groups investigated except the luminol chemiluminescence

Aging↗
PubMed1989

Hepatic actions of levonorgestrel: correlations between biochemical and morphological findings.

The influence of the synthetic sexual steroid levonorgestrel (LN) on rat liver in various doses and at different structural levels was investigated. A slight reactive hepatosis was found by histological examination after administration of LN in a dose of 10 mg per kg body wt. The same dose caused exclusively distinct lesions of the mitochondria, however, only in centrilobular parenchymal cells, whereas in the periportal hepatocytes only the lipid droplet content appears somewhat elevated. LN decreased the total glutathione content of the liver. The mitochondrial glutathione was decreased more intensively. One mg/kg body wt. of LN decreased the cytochrome P-450 content, but 10 mg/kg body wt. increased ethyl-morphine N-demethylation and 7-ethoxycoumarin O-deethylation activities. Distinct correlations could be shown between the biochemical changes and the ultrastructural findings.

Animals↗
PubMed1989

Glutathione synthesis and export in experimental liver cirrhosis induced by thioacetamide: relations to ultrastructural changes.

Micro-and macronodular experimental liver cirrhosis was induced in female rats by administration of 0.03% thioacetamide (TAA) in drinking water for 3 or 6 months, respectively. The glutathione (GSH) status (content, synthesis, export) and ultrastructural changes of liver were investigated 14 d after withdrawal of TAA. The hepatic level of GSH was increased after 6 months TAA treatment. The levels of oxidized glutathione (GSSG) were not changed after 3 months or 6 months TAA administration. The GSH synthesis was not disturbed in the cirrhotic livers; only the ratio between the 2 synthesizing enzymes was changed in macronodular liver cirrhosis. The plasma GSH content was reduced in both cases, independent of the stage of liver cirrhosis. The electron microscopic studies on cirrhotic rat livers revealed a series of characteristic structural changes, such as disorganization and total lack of the microvilli border, appearance of basement membrane-like deposits within the narrowed space of Disse, disappearance of the highly porous endothelial cell lining and partly an intensively detoriated blood supply within the pseudolobules. It is suggested that all these changes may contribute to a disturbance of the GSH export from the hepatocytes into the blood. It is very likely, however, that the alterations of the sinusoidal cell surface play the most important role. 1. The GSH/GSSG redox potential is shifted in favour of the reduced form in this cirrhosis model. This shift seems to be connected with later stages of cirrhogenesis. 2. A GSH export disturbance is responsible for the decreased plasma GSH level in liver cirrhosis.

Animals↗
PubMed1989

Influence of prenatal administration of cadmium on postnatal development and inducibility of hepatic monooxygenases in rats.

Cadmium inhibits hepatic monooxygenases in rats of different ages. But also in the offspring of dams which had received cadmium during pregnancy changes in biotransformation activities and their inducibilities could be observed. In the 30- and 60-day-old offspring a decrease in the inducibility of ethoxyresorufin O-deethylation by the specific inducer beta-naphthoflavone could be demonstrated, whereas cytochrome P-450 concentration, ethylmorphine N-demethylation and ethoxycoumarin O-deethylation were not influenced.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1989

gamma-Glutamyltranspeptidase in liver homogenates of rats of different ages: enzyme kinetics and age course of Km and Vmax.

Optimum incubation conditions for the determination of gamma-glutamyltranspeptidase with liver homogenates from rats of different ages have been determined: about 1 mg protein/assay, 4.4 mM L-gamma-glutamyl-p-nitroanilide, 40 mM glycylglycine, 9.6 mM MgCl2 in 0.1 M Tris-HCl buffer, pH 8.0; final volume 1.3 ml. The enzyme activity is very high at birth, the increase before birth is not continuous. After birth the enzyme activity decreases quickly over the first postnatal days. The ENDRENYI-KWONG-plot was linear with homogenates from newborn and 3-day-old animals. For all other age groups the graphs showed an angle. Statistical analysis carried out that a two-enzyme model plots the experimental data only insignificantly better than a one-enzyme model. It may be concluded that there are different GGT isozymes which show different affinities towards the substrate and which show different developmental patterns.

Aging↗