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At least 235 records · Page 13Linked to original sources
PubMed1986

Differential inhibition of rat tissue catalase by cyanamide.

The relative sensitivity of rat tissue catalase to inhibition by intraperitoneally administered cyanamide was liver greater than kidney greater than heart greater than brain, whereas the activity of the erythrocyte enzyme was affected minimally. The measured ED50 values for cyanamide in these tissues were 31, 44, 107 and 680 mumoles/kg body weight for liver, kidney, heart and brain respectively. On a molar basis, cyanamide was approximately twenty times more potent than 3-amino-1,2,4-triazole (3-AT) in inhibiting hepatic catalase in vivo in the rat. Like 3-AT, cyanamide inhibited erythrocyte catalase activity in vitro in the presence of hydrogen peroxide. The apparent similarities between the inhibition of hepatic catalase by cyanamide and 3-AT in vivo suggest that cyanamide belongs to the family of 3-AT-like catalase inhibitors.

Amitrole↗
PubMed1986

Catalase-dependent ethanol metabolism in vivo in deermice lacking alcohol dehydrogenase.

Pathways of ethanol elimination in alcohol dehydrogenase (ADH)-positive and -negative deermice were studied using the catalase inhibitor, 3-amino-1,2,4-triazole. To verify that aminotriazole inhibited catalase effectively, the characteristic decrease in catalase-H2O2 which occurs in saline-treated controls when ethanol is peroxidized was monitored at 660-640 nm in perfused deermouse livers. Following 1.5 hr of pretreatment with aminotriazole (1.5 g/kg), the peroxidatic activity of catalase measured in vitro was inhibited by greater than 99%. Under these conditions, ethanol did not decrease catalase-H2O2 in perfused livers, indicating that catalase was inhibited. Ethanol and aniline oxidation by microsomes were also inhibited by about 67-90% after 1.5 hr of pretreatment with aminotriazole. In ADH-positive deermice, pretreatment with aminotriazole for 1.5 hr prior to injection of ethanol (2.0 g/kg) decreased rates of ethanol elimination in vivo from 13.2 +/- 0.8 to 10.2 +/- 0.4 mmoles/kg/hr. In ADH-negative deermice, similar treatment decreased rates of ethanol elimination in vivo from 4.5 +/- 0.4 to 1.1 +/- 0.6 mmoles/kg/hr. Following pretreatment with aminotriazole (1.0 g/kg) for 6 hr, rates of ethanol elimination in ADH-negative deermice returned to near basal values. Under these conditions, the peroxidatic activity of catalase measured in vitro and the ethanol-dependent decrease in catalase-H2O2 in perfused livers also returned to near basal levels; however, the oxidation of ethanol by cytochrome P-450 was inhibited completely. It is concluded, therefore, that time of pretreatment with aminotriazole is an important variable which must be controlled carefully to inhibit catalase completely. Since catalase was active while cytochrome P-450 was not following 6 hr of pretreatment with aminotriazole, it is concluded that ethanol elimination occurs predominantly via catalase-H2O2 in ADH-negative deermice under these conditions.

Alcohol Dehydrogenase↗
PubMed1989

Hydroxylation of salicylate by activated neutrophils.

Salicylates are metabolized in vivo to hydroxylated compounds, including 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid (gentisic acid). The present study hypothesized that activated neutrophils represent one pathway for salicylate hydroxylation. Human neutrophils were incubated in medium containing 10 mM salicylate and stimulated with phorbol myristate acetate (PMA) for 1 hr. The cell-free supernatant fractions were analyzed by HPLC. Neutrophils (1 x 10(6) cells) produced 55 +/- 11 ng of gentisic acid. Neutrophils also produced smaller quantities of 2,3-dihydroxybenzoic acid. Antioxidant inhibitor experiments indicated that superoxide dismutase (SOD), heme protein inhibitors, and glutathione blocked gentisic acid formation, whereas catalase, mannitol, and deferoxamine failed to inhibit. Experiments with the reagent hypochlorous acid (HOCl) and the model myeloperoxidase (MPO) enzyme system did not support a role for the MPO pathway in gentisic acid formation. These findings demonstrate that activated neutrophils can hydroxylate salicylate by an unknown pathway. This pathway may contribute to the increased recovery of hydroxylated salicylates in patients with inflammatory disorders.

Amitrole↗
PubMed1991

Dose- and time-dependent effect of an acute 3-amino-1,2,4-triazole injection on rat brain catalase activity.

The results presented in this study demonstrate a progressive inhibition of rat brain catalase activity by AT in vivo. Furthermore, the inhibition of brain catalase by AT demonstrates the presence of hydrogen peroxide in brain, since AT inhibits catalase in the presence of this compound. The rate of inhibition of catalase seems to be dependent upon the rate by which H2O2 is generated. A time course study showed slower onset of the inhibition of brain as compared to liver catalase, possibly reflecting tissue hydrogen peroxide levels or, alternatively, a rate-limiting penetration of AT into brain and into the catalase compartment. The presence of AT in brain was confirmed over the time period of the observed inhibition of brain catalase. Catalase inhibitors are of particular interest in the study of the physiological role of catalase. This study further supports the use of AT in investigations designed to further understand the role of brain catalase.

Amitrole↗
PubMed1992

Ethanol metabolism in rat brain homogenates by a catalase-H2O2 system.

Homogenates of perfused rat brains incubated in the presence of ethanol (50-100 mM) and glucose (10 mM) were found to oxidize ethanol to acetaldehyde. The addition of glucose oxidase, a known hydrogen peroxide generator, to the incubation medium, significantly (P less than 0.05) increased the generation of acetaldehyde. The presence in the incubation medium of metyrapone, an inhibitor of cytochrome P450, or pyrazole, an alcohol dehydrogenase inhibitor, did not affect the levels of acetaldehyde obtained. Conversely, the presence of 3-amino-1,2,4-triazole, a known catalase inhibitor, induced a concentration-dependent reduction of the amount of acetaldehyde generated after incubation, even in the presence of glucose oxidase. Homogenates of perfused brains of rats treated with 3-amino-1,2,4-triazole or cyanamide (another H2O2-dependent catalase blocker) also showed a dose-dependent reduction of the acetaldehyde obtained. These findings support the notion that a catalase-mediated oxidation of ethanol is present in rat brain homogenates. It is suggested that this local oxidation of ethanol may have important biological implications. The data of both studies increase support for the notion that acetaldehyde is produced directly in the brain and that it may be the agent mediating some of the psychopharmacological properties of ethanol and be one of the factors determining the propensity of an animal to voluntarily consume ethanol.

Acetaldehyde↗
PubMed1992

Plasma membrane as a site of redox activation of daunomycin in intact human erythrocytes. Quantitative evaluation of the hydrogen peroxide produced by the membrane with respect to the cytosol.

The relative importance in human red blood cells of the plasma membrane as a site of redox activation of anthracyclines as compared to hemoglobin was evaluated by assaying the H2O2 produced upon exposure to daunomycin. The method of H2O2-dependent irreversible inhibition of catalase (EC 1.11.1.6) activity by 3-amino-1,2,4-triazole was applied to intact erythrocytes, as well as to isolated membranes with added purified catalase. The results obtained indicate a secondary role in daunomycin activation for the plasma membrane from a quantitative point of view, although membrane pathways can be more harmful than cytosolic pathways, especially towards extracellular targets, when the high efficiency of the cytosolic antioxidative defences and the external location of the membrane activation site are considered.

Amitrole↗
PubMed1993

Aminoguanidine: a drug proposed for prophylaxis in diabetes inhibits catalase and generates hydrogen peroxide in vitro.

Aminoguanidine (AG) has been proposed as a drug of potential benefit in prophylaxis of the complications of diabetes. We show here that AG irreversibly inhibits catalase with an efficacy similar to aminotriazole. AG also produces hydrogen peroxide, in a transition metal-catalysed process which may be partially dependent upon prior hydrolysis of AG to semicarbazide and hydrazine. These observations may be of importance in proposals for the long term administration of AG in diabetes.

Amitrole↗
PubMed1993

Increase in liver microsomal glutathione S-transferase activity by phenobarbital treatment of rats. Possible involvement of oxidative activation via cytochrome P450.

The possible involvement of oxidative activation of liver microsomal glutathione (GSH) S-transferase by the cytochrome P450 system was investigated. When rats were given phenobarbital (PB) intraperitoneally for 3 days, liver microsomal GSH S-transferase activity was stimulated 1.3-1.4-fold and the effect of PB on the transferase was potentiated by combination with a catalase inhibitor, 3-amino-1,2,4-triazole. Immunoblotting of microsomal proteins from PB-treated rats with anti-microsomal GSH S-transferase antibody after SDS-PAGE showed the presence of a dimer of the transferase. When microsomal suspensions prepared from PB-treated rats were placed on ice without GSH, the microsomal GSH S-transferase activity gradually increased with time and reached 200% of the initial level at 3 hr when activation of the transferase by N-ethylmaleimide was lost. The time-dependent increase in GSH S-transferase activity in PB-treated microsomes was prevented by addition of 0.1 mM GSH. The increase in microsomal GSH S-transferase activity by NADPH was depressed by cytochrome P450 inhibitors such as SKF 525-A (2-diethylaminoethyl-2,2-diphenylvalerate), metyrapone or isoniazid in agreement with the concomitant decrease in generation of hydrogen peroxide in microsomes. These results indicate that the increase in GSH S-transferase activity in liver microsomes by PB treatment of rats is due to the oxidative modification of the enzyme by reactive oxygen species which are concomitantly increased following induction of cytochrome P450.

Amitrole↗
PubMed1994

Aminotriazole is a potent inhibitor of alpha-oxidation of 3-methyl-substituted fatty acids in rat liver.

The production of CO2 and formate in isolated rat hepatocytes incubated in the presence of 3-methyl[1-14C]margaric acid was investigated. Production rates of formate were approximately 4-fold lower than those of CO2. Aminotriazole (3-amino-1, 2, 4-triazole), an irreversible inhibitor of catalase, potently suppressed alpha-oxidation of 3-methylmargaric acid, whereas beta-oxidation of palmitate, 2-methylpalmitate and trihydroxycoprostanic acid and conversion of exogenously added formate to CO2 were not or only slightly affected. This shows that aminotriazole is not only an inhibitor of catalase, but also of alpha-oxidation of 3-methyl-substituted fatty acids.

Amitrole↗