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A I Cederbaum

Publications and source records attributed to A I Cederbaum.

At least 181 records · Page 10Linked to original sources
PubMed1982

Role of catalase and hydroxyl radicals in the oxidation of methanol by rat liver microsomes.

In view of the presence of adventitious catalase in isolated microsomes, and the requirement for H2O2, it has been suggested that NADPH-dependent oxidation of methanol by rat liver microsomes was mediated exclusively by the peroxidatic activity of catalase. However, H2O2 may also serve as a precursor of the hydroxyl radical, and methanol reacts with hydroxyl radicals to produce formaldehyde. Inhibition of H2O2 production should therefore decrease methanol oxidation by either a hydroxyl radical-dependent pathway or a catalase-dependent pathway. To attempt to clarify some of the controversies concerning the roles of H2O2 and catalase in the microsomal pathway of oxidation of short chain alcohols, studies were carried out to determine the nature of the pathway responsible for methanol oxidation by isolated microsomes. In the absence of the catalase inhibitor azide, methanol may be oxidized primarily by the peroxidatic activity of catalase since there was little effect on methanol oxidation by competing hydroxyl radical scavengers. Azide, which inhibited catalase activity greater than 95%, inhibited NADPH-dependent oxidation of methanol by 30-50%. The azide-insensitive (catalase-independent) pathway of methanol oxidation was inhibited by scavengers of hydroxyl radicals. The inhibition of the scavengers reflected the rate constant for interaction with hydroxyl radicals and was greater at lower concentrations of methanol than at higher concentrations, suggesting competition between the scavengers and methanol. The addition of H2O2 stimulated the oxidation of methanol in the presence of azide; H2O2 may serve as a precursor of the hydroxyl radical. Iron-EDTA, which is known to increase hydroxyl radical production, stimulated the oxidation of methanol in the absence and presence of azide. The stimulation by iron-EDTA was blocked by the competing hydroxyl radical scavengers even in the absence of azide, suggesting that the added iron-EDTA favorably with microsomal catalase for H2O2 to produce hydroxyl radicals (or a species with the oxidizing power of the hydroxyl radical). These results suggest that in microsomes, depending on the absence or presence of azide, methanol may be oxidized by two primary pathways, one involving the peroxidatic activity of catalase, and the other in which hydroxyl radicals, generated from microsomal electron transfer, play a role. In view of the crucial role played by H2O2 in both pathways, inhibition of H2O2 formation should not be interpreted solely as evidence for a role for catalase in the microsomal oxidation of alcohols.

Animals↗
PubMed1982

Abnormal serum transaminase levels in patients with hemophilia A.

In a cooperative study of 1,332 hemophiliacs, the results of a variety of liver function tests were correlated with the intensity and type of exposure to plasma products. After three sets of measurements of six-month intervals, 72% of patients had at least one abnormal transaminase value and 21.1% and 23.6% of patients had persistently elevated SGOT and SGPT levels, respectively, on all three measurements. Patients who had received no factor VIII during the previous year had fewer abnormalities than treated patients. Only those treated patients who received less than 50 units of factor VIII per kilogram per six months had fewer transaminase abnormalities if they used cryoprecipitate than if they used concentrate, but these patient groups are not strictly comparable, in that the cryoprecipitate-treated group contained a higher proportion of patients with mild hemophilia than did the concentrate-treated group.

Alanine Transaminase↗
PubMed1981

The effect of cyanamide on acetaldehyde oxidation by isolated rat liver mitochondria and on the inhibition of pyruvate oxidation by acetaldehyde.

Compared to other substrates, the oxidation of pyruvate by isolated mitochondria is especially sensitive to inhibition by acetaldehyde. It is not known whether this inhibition represents a direct effect of acetaldehyde or requires the metabolism of acetaldehyde. Experiments were therefore carried out in the presence of cyanamide, an inhibitor of aldehyde dehydrogenase. After a brief incubation period, cyanamide inhibited the state 4 and state 3 rate of acetaldehyde (0.1-1.0 mM) oxidation by isolated rat liver mitochondria. Little inhibition was found in the absence of the incubation period. Maximum inhibition was found at cyanamide concentrations of 0.01 to 0.033 mM. Cyanamide also inhibited the activity of aldehyde dehydrogenase assayed in disrupted mitochondrial fractions. The inhibition by cyanamide was specific since cyanamide did not affect mitochondrial oxidation of succinate, glutamate, or pyruvate. Acetaldehyde inhibited the state 3 rate of pyruvate oxidation by liver mitochondria. Despite preventing acetaldehyde oxidation, cyanamide did not prevent the inhibition of pyruvate oxidation by acetaldehyde. These results indicate that (a) cyanamide can be used as an effective in vitro inhibitor of acetaldehyde oxidation and (b) the unique sensitivity of pyruvate oxidation to acetaldehyde represents a direct effect of acetaldehyde on pyruvate dehydrogenase.

Acetaldehyde↗
PubMed1980

Role of hydroxyl radicals in the iron-ethylenediaminetetraacetic acid mediated stimulation of microsomal oxidation of ethanol.

The microsomal oxidation of ethanol or 1-butanol was increased by ferrous ammonium sulfate-ethylenediaminetetraacetic acid (1:2) (Fe-EDTA) (3.4-50 microM). The increase was blocked by hydroxyl radical scavenging agents such as dimethyl sulfoxide or mannitol. The activities of aminopyrine demethylase or aniline hydroxylase were not affected by Fe-EDTA. The accumulation of H2O2 was decreased in the presence of Fe-EDTA, consistent with an increased utilization of H2O2. Other investigators have shown that Fe-EDTA increases the formation of hydroxyl radicals in systems where superoxide radicals are generated. The stimulation by Fe-EDTA appears to represent a pathway involving hydroxyl radicals rather than catalase because (1) stimulation occurred in the presence of azide, which inhibits catalase, (2) stimulation occurred in the presence of 1-butanol, which is not an effective substrate for catalase, and (3) stimulation was blocked by hydroxyl radical scavenging agents, which do not affect catalase-mediated oxidation of ethanol. A possible role for contaminating iron in the H2O or buffers could be ruled out since similar results were obtained with or without chelex-100 treatment of these solutions. The stimulatory effect by Fe-EDTA required microsomal electron transfer with NADPH, and H2O2 could not replace the NADPH-generating system. In the absence of microsomes or catalase, Fe-EDTA also stimulated the coupled oxidation of ethanol during the oxidation of xanthine by xanthine oxidase. These results suggest that during microsomal electrom transfer, conditions may be appropriate for a Fenton type or a modified Haber-Weiss type of reaction to occur, leading to the production of hydroxyl radicals.

Animals↗
PubMed1980

Role of hydroxyl radicals in microsomal oxidation of alcohols.

A series of hydroxyl radical (.OH) scavenging agents competitively inhibited microsomal oxidation of ethanol and 1-butanol. The inhibition by the scavengers was specific since these agents had no effect on catalase-dependent oxidation of ethanol, microsomal drug metabolism or microsomal electron transfer. Chemical evidence for production of .OH during microsomal electron transfer was provided by the generation of appropriate products from .OH scavenging agents. H2O2 was shown to play a role as a precursor of .OH. Fe-EDTA increased microsomal oxidation of ethanol without affecting drug metabolism. A role for cytochrome P-450 in catalyzing . OH generation remains to be evaluated. These results suggest that the molecular mechanism underlying the oxidation of ethanol by liver microsomes reflects the ability of ethanol to interact with .OH generated from microsomal electron transfer.

Alcohols↗
PubMed1980

Renal cell carcinoma in polycystic kidneys: case report and review of literature.

A case of polycystic kidneys associated with a sarcomatoid variant of renal cell carcinoma is reported. The patient presented with hilar lymphadenopathy, para-aortic lymph node enlargement with an abnormal lymphangiogram and splenomegaly. Biopsy of the hilar lymph node, para-aortic lymph node and spleen showed reactive hyperplasia only but biopsy of the left kidney, liver and mesentery revealed poorly differentiated renal cell carcinoma with sarcomatous changes.

Adenocarcinoma↗
PubMed1980

Oxidoreductase activities in normal rat liver, tumor-bearing rat liver, and hepatoma HC-252.

Experiments were carried out to determine if the difference in rates of cell proliferation between normal and neoplastic cells may be related to altered levels of oxidative enzymes. Assays were performed using homogenates from hepatocellular carcinoma HC-252, a rapidly growing and moderately well-differentiated tumor; from normal liver; and from the liver of the tumor-bearing ACI rat. Results of the mitochondrial enzymes indicated that the activities of cytochrome oxidase and succinate dehydrogenase were 3-fold lower in tumor homogenates than in liver homogenates. Monoamine oxidase activity could not be detected in HC-252; mixing experiments indicated no inhibitor was present in HC-252. Activities of th peroxisomal enzymes, urate oxidase, D-amino acid oxidase, and L-alpha-hydroxy acid oxidase were either undetected in the tumor or were 12-fold lower than in liver homogenates. The activity of xanthine oxidase, a cytoplasmic enzyme, was 5- to 6-fold lower in the tumor. Catalase activity in the tumor was also lower than in liver; this may be indicative of a lower oxidative environment at the cellular level. These enzyme activities of the liver of tumor-bearing rats were in the same range as those of normal rat liver, except that D-amino acid oxidase activity was slightly lower, and catalase activity was markedly lower and varied in a wide range. These results show an inverse correlation between the activities of oxygen-utilizing enzymes and rates of proliferation of one tumor line and its control. The possible implications of these results in neoplasia, cell proliferation, and cellular aging are discussed.

Animals↗