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Biomedical subjects

O R Koch

Publications and source records attributed to O R Koch.

At least 19 recordsLinked to original sources
PubMed1997

Regression of morphological alterations and oxidative stress-related parameters after acute lindane-induced hepatotoxicity in rats.

Changes in rat liver oxidative stress-related parameters, morphological alterations, as well as circulating and tissue levels of lindane were studied 1-7 days after the administration of a single dose of 60 mg of lindane/kg. One day after lindane treatment, a significant enhancement in the oxidative stress status of the liver was observed, characterized by an increase in thiobarbituric acid reactants production and in the microsomal generation of superoxide radical (O.-2) coupled to cytochrome P450 induction, and a decrement in the activity of superoxide dismutase (SOD) and catalase. Consequently, the O.-2 production/SOD activity ratio was enhanced two-fold. In this condition, light microscopy studies revealed the incidence of liver lesions in periportal areas, together with significant changes at the mitochondrial level observed by electron microscopy, which coincide with the maximal levels of lindane in the liver, adipose tissue, plasma and whole blood. Changes in oxidative stress-related parameters observed after 1 day of lindane treatment regressed to normal from the third day and thereafter, together with the decrement in circulating and tissue levels of the insecticide. It is concluded that morphological and oxidative stress-related changes induced in the liver by acute lindane intoxication are readily reversible, depend on the hepatic content of the insecticide, and seem to be conditioned by the changes in O.-2 generation.

Adipose Tissue↗
PubMed1997

Pro- and anti-oxidant parameters in rat liver after short-term exposure to hexachlorobenzene.

The association between an in vivo oxidative stress condition of the liver and hepatic porphyria during HCB intoxication is postulated. After 30 days of treatment, HCB (25 mg/kg b.w.) promotes an induction of microsomal cytochrome P450 system, increase in microsomal superoxide anion generation accompanied by increased levels of liver lipid peroxidation, as measured by the production of thiobarbituric acid reactants and by spontaneous visible chemiluminescence. Concomitantly, liver antioxidant defenses are slightly modified, with decreased activity of glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase contributing to an oxidative stress condition of the liver. These liver biochemical alterations are closely related to increased levels of urinary coproporphyrin, plasma AST and ALT activities and to the onset of liver morphological lesions.

Animals↗
PubMed1994

Ethanol treatment up-regulates the expression of mitochondrial manganese superoxide dismutase in rat liver.

On the basis of the well-known effect of ethanol poisoning on the prooxidant/antioxidant balance of human and rodent liver we tested the response of the mitochondrial manganese-containing superoxide dismutase (MnSOD) in the liver of rats following an acute ethanol load or chronically intoxicated with an alcohol-supplemented solid diet for three weeks. In both conditions the enzyme activity and messenger RNA were monitored. In the acutely treated animals MnSOD was induced (post-)translationally already at 3 hours after ethanol injection, reached the maximum level (about 50% increment) at 9 hours and decreased thereafter. Chronic ethanol feeding caused an up-regulation of the enzyme at the mRNA level, with a good correlation between the transcript and the enzyme activity during the first two weeks of treatment. After 20 days the mRNA level dropped to normal, whereas the activity still remained high. Chronic alcohol intake also led to a significant decrease in the content of vitamin E in the liver mitochondrial and microsomal fractions, suggesting the occurrence of an enhanced lipid peroxidation, consequent to the ethanol-induced oxidative stress. The response of MnSOD appears to be a protective mechanism that the genetic machinery builds up to partially overcome such a condition.

Acute Disease↗
PubMed1991

Alcohol-induced oxidative stress in rat liver.

1. Livers from rats treated acutely with ethanol showed increased chemiluminescence, malondialdehyde production, and diene formation. Previous administration of (+)-cyanidanol-3 completely abolished acute ethanol-induced chemiluminescence. 2. Rats fed alcohol liquid diets for 3 weeks showed significant increases in microsomal and mitochondrial malondialdehyde formation, and in microsomal H2O2 and O2-. generation. 3. Rats fed a solid basal diet plus ethanol solution for 12 weeks also showed increased microsomal production of O2-. and increased content of microsomal cytochrome P-450. Hydroperoxide-induced chemiluminescence was higher in homogenates, mitochondria and microsomes from ethanol-treated rats than from controls. Vitamins E and A were more effective inhibitors of hydroperoxide-stimulated chemiluminescence in liver homogenates from ethanol-treated rats than from control animals. 4. Results are consistent with peroxidative stress leading to increased lipid peroxidation in liver of rats fed ethanol both acutely and after long-term dosing.

Animals↗
PubMed1988

Liver and heart mitochondria in rats submitted to chronic hypobaric hypoxia.

Mitochondrial mass was determined in the heart and liver of rats submitted to 4,400 m (simulated altitude) for 9 mo and their controls at sea level. This was done 1) by evaluation of isolated mitochondrial protein per gram of tissue, 2) by evaluation of the ratio between cytochrome oxidase activity in tissue homogenate and in isolated mitochondria, and 3) by evaluation of mitochondrial numerical and volume density in fixed tissues analyzed by electron microscopy. An increase in mitochondrial mass and a more homogeneous distribution of mitochondria were found in liver. In cardiac tissue an increase in numerical density of mitochondria accompanied by a slight decrease in their mean volume was observed. Maximal physiological rate of mitochondrial respiration (state 3, active respiration), resting respiration, ADP/O, and acceptor control ratio were determined in the isolated mitochondria. No differences were found in the intrinsic properties of mitochondria. The results suggest that chronic mild hypoxia promotes tissue adaptation by increasing the mitochondrial mass or number in liver and heart, respectively, and improves intracellular O2 diffusion by adopting a more homogeneous intracellular distribution of mitochondria in the liver.

Animals↗
PubMed1988

Lindane-induced oxidative stress. I. Time course of changes in hepatic microsomal parameters, antioxidant enzymes, lipid peroxidative indices and morphological characteristics.

1. Lindane (60 mg/kg) administered orally to rats increased liver cytochrome P-450 content and superoxide radical (O2-.) generation 24 h after treatment, while formation of thiobarbituric acid reactants and NADPH/ADP-supported microsomal chemiluminescence were significantly increased 4 h after treatment. 2. Hepatic superoxide dismutase (SOD) and catalase decreased 6 h after lindane treatment and SOD/O2-. ratio progressively decreased during 4 to 24 h after lindane treatment. 3. Morphological evidence of hepatic cell injury after lindane treatment was seen at all times studied, and appeared to increase with time. 4. Lindane administration results in time-dependent oxidative stress in liver which involves an early component (4-6 h) related to the reductive metabolism of lindane, and a late component (24 h) associated with the induction of cytochrome P-450; the biochemical changes correlated with the observed morphological lesions.

Animals↗
PubMed1987

Effect of vitamin E- and selenium-deficiency on rat liver chemiluminescence.

The role of vitamin E and selenium as protective agents against oxidative stress was evaluated by measuring liver chemiluminescence in situ. Weanling rats fed a vitamin E- and selenium-deficient diet showed liver chemiluminescence that was increased 60 and 100% over control values at 16 and 18 days respectively after weaning. At day 21, the double deficiency led to hepatic necrosis, as observed by optical and electron microscopy, and increased serum levels of lactate dehydrogenase and alanine aminotransferase. Single deficiencies, in either vitamin E or selenium, did not produce liver necrosis but increased liver chemiluminescence. Vitamin E deficiency led to a 23 and 50% increase in liver emission at days 18 and 20 respectively; selenium deficiency produced a 64% increase at day 16. The activity of liver selenium-glutathione peroxidase diminished to 13% of the control value in the rats fed doubly deficient and selenium-deficient diets. Activities of superoxide dismutase, catalase and non-selenium-glutathione peroxidase were not modified by the different diets. These results suggest that oxy-radical generation may play a major role in hepatic necrosis in vitamin E- and selenium-deficiency.

Animals↗
PubMed1984

[Liver ultrastructure in congenital atresia of the extrahepatic bile ducts].

Seven patients with diagnosis of biliary atresia (BA) and two patients with neonatal hepatitis were studied by electron microscopy. In all patients the diagnosis was done by clinical examinations, laboratory assays, histological studies by punch or surgical biopsies and or surgical examinations combined with intraoperatory cholangiography. The ultrastructural alterations found in both groups of patients were essentially similar to those described in other forms of cholestasis. In patients suffering from biliary atresia the main features found at hepatocytic livel were: Finely granular deposits of electron dense substance sometimes conforming lamellar structures; 2) Some increase and vesiculation of smooth endoplasmic reticulum membranes; 3) Reductions in number and length of sinusoidal microvilli; in some areas was also detected basal membrane and an increase in the amount of collagen fibers in the space of Disse; 4) Marked bile canaliculi dilatations with reduction of microvilli and thickening of the pericanalicular surrounding area, some canaliculi were constitued by several hepatocytes. Ductules were found in only 3 cases with the following alterations: 1) Intracytoplasmic electron dense deposits of granular material without limiting membranes; 2) A marked increase in the number of microfilaments mainly located in the apical portion of the cell or in the vicinity of the nuclei; 3) Inflammatory cells in the duct epithelium or in direct contact with the hepatocytes. The ultrastructural findings in the two cases of neonatal hepatitis (NH) resembled those described in the biliary atresia.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Ducts↗
PubMed1983

Increased chemiluminescence and superoxide production in the liver of chronically ethanol-treated rats.

Rats fed ethanol (1.74 +/- 0.12 g/day/100 g body wt for 12 weeks) showed a 45% increased microsomal production of O-2 (2.23 +/- 0.14 nmol/min/mg protein) and a 28% increased content of endoplasmic reticulum protein (26.8 +/- 1.4 mg/g liver). This could lead, at substrate saturation, to a 86% increased cytosolic production of O-2 which is not compensated by cytosolic superoxide dismutase levels that remain normal. It is claimed that this unbalance between O-2 production and superoxide dismutase leads to a peroxidative stress in agreement with the 54% increased spontaneous liver chemiluminescence (37 +/- 2 cps/cm2) measured in the ethanol-treated rats. Hydroperoxide-induced chemiluminescence was 57, 43, and 28% higher, respectively, in homogenates, mitochondria, and microsomes isolated from ethanol-treated rats as compared with controls. Vitamins E and A were more effective inhibitors of the hydroperoxide-stimulated chemiluminescence in the liver homogenates from ethanol-treated rats as compared with the effect on the homogenates from control animals. The results are consistent with a peroxidative stress in chronic alcoholism leading to increased lipoperoxidation and decreased levels of antioxidants.

Animals↗
PubMed1983

Hepatic alterations in rats fed ethanol at two levels of lipotropes.

Two groups of rats were fed for 4 months either a lipotrope deficient (E-D) or a lipotrope supplemented (E-S) diet, both containing about 30% of total calories as ethanol (E). Two control groups consumed similar lipotrope deficient (S-D) and lipotrope supplemented (S-S) diets, but with sucrose (S) replacing ethanol. The rate of ethanol disappearance, microsomal protein content and total microsomal H2O2 generation were about 50% higher in the E-D group than in the other groups. Morphological studies revealed moderate to severe fatty changes only in the livers of the lipotrope deficient groups (E-D; S-D), while mitochondrial enlargement was observed only in the alcohol fed groups (E-S; E-D), particularly in the E-S group. State 3 respiratory rates with succinate and with malate-glutamate as substrates were about 50% reduced in the liver mitochondria of the animals of the E-S group, as compared with the other groups. From these results it is inferred that the lipotrope supplemented diet effectively prevented the alcoholic fatty liver but counteracted the alcohol-associated increases of ethanol oxidation rate, microsomal protein content and total microsomal H2O2 generation. On the other hand, the lipotrope supplemented diet was a necessary factor for the impairment of the mitochondrial respiratory function observed after chronic ethanol feeding.

Animals↗
PubMed1979

[Hepatic function in vivo and in the isolated liver of rats poisoned with parathion].

Enzyme determinations and hepatic histological studies were carried out in normal rats and in rats intoxicated with the organophosphorus pesticide parathion. No significative evidence of hepatocellular damage was seen in parathion -- intoxicated rats as responsible of the impaired bile flow and sulfobromophthalein biliary excretion that were previously reported. On the contrary, the isolated perfused rat liver from normal and intoxicated rats showed a similar behavior when the perfusate flow through the liver was maintained at a similar rate. We conclude that altered hepatic blood flow may be a factor determinant of an impairment of bile flow and of biliary excretion of several organic anions like sulphobromopthalein that were observed in parathion -- intoxicated rats.

Alanine Transaminase↗