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At least 19 recordsLinked to original sources
PubMed2005

Expression of a fungal cyanamide hydratase in transgenic soybean detoxifies cyanamide in tissue culture and in planta to provide cyanamide resistance.

Embryogenic tissue cultures of soybean were transformed by particle bombardment with a vector pCHZ-II that carries the coding sequence for cyanamide hydratase (Cah), an enzyme that converts toxic cyanamide to urea, from the soil fungus Myrothecium verrucaria. The Cah gene was driven by the constitutive Arabidopsis thaliana actin-2 promoter and terminated with its cognate terminator. This vector also carries the hygromycin phosphotransferase gene (hpt) driven by the potato (Solanum tuberosum) ubiquitin-3 promoter. Twelve individual lines of transgenic plants that were obtained under hygromycin selection expressed Cah mRNA and exhibited resistance to hygromycin in leaf tissue culture, while the untransformed tissues were sensitive. Cah enzyme activity was present in extracts of transformed leaves and embryogenic tissue cultures when measured by a colorimetric assay and the presence of the Cah protein was confirmed by enzyme-linked immunosorbent assay (ELISA). Cah expression detoxified cyanamide in leaf callus and embryogenic cultures as well as in whole plants as shown by cyanamide resistance. The Cah-expressing plants grew and set seeds normally indicating that the Cah enzyme activity did not affect soybean plant metabolism. We also describe a test whereby callus was formed on cultured leaf tissue in the presence of hygromycin or cyanamide only if the hpt or Cah gene was expressed, respectively. This test is a convenient and cost-effective way to follow the marker gene in the primary regenerated plants and subsequent generations, which is particularly reliable for the hpt gene expression using hygromycin.

Cyanamide↗
PubMed2005

Direct quantitative determination of cyanamide by stable isotope dilution gas chromatography-mass spectrometry.

Cyanamide is a multifunctional agrochemical used, for example, as a pesticide, herbicide, and fertilizer. Recent research has revealed that cyanamide is a natural product biosynthesized in a leguminous plant, hairy vetch (Vicia villosa). In the present study, gas chromatography-mass spectrometry (GC-MS) equipped with a capillary column for amines was used for direct quantitative determination of cyanamide. Quantitative signals for ((14)N(2))cyanamide, ((15)N(2))cyanamide (internal standard for stable isotope dilution method), and m-(trifluoromethyl)benzonitrile (internal standard for correcting errors in GC-MS analysis) were recorded as peak areas on mass chromatograms at m/z 42 (A(42)), 44 (A(44)), and 171 (A(IS)), respectively. Total cyanamide content, ((14)N(2))cyanamide plus ((15)N(2))cyanamide, was determined as a function of (A(42)+A(44))/A(IS). Contents of ((14)N(2))cyanamide and ((15)N(2))cyanamide were then calculated by multiplying the total cyanamide content by A(42)/(A(42)+A(44)) and A(44)/(A(42)+A(44)), respectively. The limit of detection for the total cyanamide content by the GC-MS analysis was around 1ng. The molar ratio of ((14)N(2))cyanamide to ((15)N(2))cyanamide in the injected sample was equal to the observed A(42)/A(44) value in the range from 0.1 to 5. It was, therefore, possible to use the stable isotope dilution method to quantify the natural cyanamide content in samples; i.e., the natural cyanamide content was derived by subtracting the A(42)/A(44) ratio of the internal standard from the A(42)/A(44) ratio of sample spiked with internal standard, and then multiplying the resulting difference by the amount of added ((15)N(2))cyanamide (SID-GC-MS method). This method successfully gave a reasonable value for the natural cyanamide content in hairy vetch, concurring with the value obtained by a conventional method in which cyanamide was derivatized to a photometrically active compound 4-cyanimido-1,2-naphthoquinone and analyzed with reversed-phase HPLC (CNQ-HPLC method). The determination range of cyanamide in the SID-GC-MS method was almost the same as that in the CNQ-HPLC method; however, the SID-GC-MS method was much simpler than the CNQ-HPLC method.

Cyanamide↗
PubMedDate not supplied

Catalase mediated conversion of cyanamide to an inhibitor of aldehyde dehydrogenase.

A minor pathway for cyanamide metabolism catalyzed by catalase is responsible for the conversion of cyanamide to an inhibitor of aldehyde dehydrogenase. Catalase itself is also inhibited by cyanamide. Both the activation of cyanamide by catalase and the inhibition of catalase by cyanamide were blocked in vivo by ethanol pretreatment, suggesting that these two processes are closely linked. Like other catalase oxidation reactions, the catalase mediated activation of cyanamide was inhibited by 3-amino-1,2,4-triazole in vivo and sodium azide in vitro. The relative formation of the active cyanamide metabolite was assessed in vitro by following the loss of yeast aldehyde dehydrogenase activity with time. Inhibition of the yeast enzyme by activated cyanamide was dependent on NAD+ or NADP+, a requirement not fulfilled by NADH or NADPH. Although H2O2 inhibited yeast aldehyde dehydrogenase in vitro and cyanamide inhibited hepatic catalase in vivo, the possible in hepatic H2O2 concentration following cyanamide administration does not account for the effects of cyanamide on ethanol metabolism. While the cyanamide activating enzyme has been identified as catalase, the reaction products of this reaction and, in particular, the structure of the active metabolite involved in the inhibition of aldehyde dehydrogenase remain unknown.

Aldehyde Dehydrogenase↗
PubMed2000

Comparison of cyanamide and disulfiram in effects on liver function.

BACKGROUND: Cyanamide, an aversive drug widely used in Japan, develops ground-glass inclusion bodies in the hepatocytes at high incidences, which may be associated with portal inflammation and fibrosis. When cyanamide-treated alcoholics relapse drinking, the combined effect of cyanamide and alcohol produce more severe portal inflammation along with the emergence of ground-glass inclusions. Disulfiram also causes hepatitis, but there have been no comparative studies of effects of cyanamide and disulfiram on liver function. METHODS: We reviewed the laboratory data of 408 alcoholics admitted for a 3 month course of alcohol detoxification and rehabilitation. Patients tested negative for hepatitis virus markers and were diagnosed as not having cirrhosis. Among the subjects, 222 patients received cyanamide treatment (a daily dose of 70 mg) without a history of disulfiram treatment, and 186 received disulfiram (a daily dose of 200 mg) without a history of cyanamide treatment. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels obtained at 0, 4, 8, and 12 weeks of administration of each aversive drug were compared between the two alcoholic groups. RESULTS: Elevation of serum transaminases (AST > ALT) probably due to alcoholic liver disease quickly fell after abstinence. In patients who took cyanamide, the ALT levels were significantly higher at 4 and 12 weeks than in those who took disulfiram. Re-elevations of ALT after alcohol detoxification were more frequently observed in those who took cyanamide than in those who took disulfiram (19.4% vs. 5.9%, p < 0.001). The re-elevations of ALT were slight to moderate, being more than 3-fold in three (1.4%) patients who took cyanamide and four (2.2%) who took disulfiram. The re-elevations occurred more frequently in those with a history of cyanamide treatment before the present treatment than in those who took cyanamide for the first time (31.1% vs. 16.4%, p < 0.05). CONCLUSIONS: Cyanamide, compared with disulfiram, was more frequently associated with elevations of ALT that persisted after abstinence.

Adult↗
PubMed1983

Metabolic activation of cyanamide to an inhibitor of aldehyde dehydrogenase in vitro.

The inhibition of aldehyde dehydrogenase (AIDH) by cyanamide is dependent on the conversion of the latter to an active metabolite. This accounts for the in vivo activity of cyanamide in raising ethanol-derived blood acetaldehyde levels to the mM range in the rat (ED50 for cyanamide = 0.11 mmole/kg) and its lack of inhibitory activity in vitro with purified AIDH enzymes. Liver mitochondria were shown to catalyze this activation. The Low Km mitochondrial AIDH isozyme was strongly inhibited by cyanamide when measured in intact rat liver mitochondria (I50 = 2.0 microM). Cyanamide also inhibited yeast AIDH when incubated in the presence, but not in the absence, of rat liver mitochondria (I50 = 7.8 microM). Using yeast AIDH activity as a measure of cyanamide activation, the subcellular distribution of the cyanamide-activating system was assessed. Microsomes plus an NADPH generating system were equally active as mitochondria in activating cyanamide. In the absence of NADPH, microsomal activity was about half that of mitochondria. Little or no activity was found in the cytosolic fraction. A series of cyanamide analogs and derivatives were screened for their ability to inhibit the low Km AIDH isozyme measured in intact mitochondria. Only monoalkylcyanamides exemplified by n-butylcyanamide showed significant inhibition. Other cyanamide analogs and derivatives including N-acetylcyanamide, the major urinary metabolite of cyanamide, were inactive in this system.

Acetaldehyde↗
PubMed1985

Enzymatic requirement for cyanamide inactivation of rat liver aldehyde dehydrogenase.

The in vitro inactivation of aldehyde dehydrogenase (ALDH) by cyanamide in rat liver slices, in intact mitochondria, and at various stages of purity was characterized. Low-Km ALDH was more susceptible to cyanamide inactivation than was the high-Km form. In addition, the presence of NAD or NADH was necessary for cyanamide inhibition of the ALDH activity. Cyanamide at low concentrations required enzymatic conversion to a reactive derivative that could inhibit ALDH. The data in this study are consistent with the suggestion of DeMaster et al. [Biochem. biophys. Res. Commun., 122, 358 (1984)] that catalase is the cyanamide-converting enzyme. An inhibitor of catalase activity, malonate, decreased the rate of cyanamide inactivation of ALDH in intact mitochondria. Furthermore, affinity chromatography-purified ALDH, free of catalase activity, was not susceptible to cyanamide inactivation. This affinity-purified ALDH was only inactivated by high concentrations of cyanamide. Thus, an alternative pathway for ALDH inactivation may exist in which enzymatic modification of cyanamide is not necessary. It is more likely, however, that a contaminating enzyme in the ALDH preparation is capable of activating cyanamide.

Aldehyde Dehydrogenase↗
PubMed2000

Ethanol patch test: a simple method for identifying the effectiveness of cyanamide in alcoholics.

BACKGROUND: To identify the pharmacological effectiveness of cyanamide, 144 alcoholics treated with cyanamide were subjected to a test that used an acetaldehyde dehydrogenase (ALDH) inhibitor, the ethanol patch test, which is considered to be a good indicator of ALDH2 phenotype. METHODS: We placed 100 microl of 70% ethanol on a lint pad and, as a control, placed the same volume of distilled water on a second pad. The ethanol patch test was performed on 144 alcoholics more than 2 weeks after abstinence from alcohol before and after treatment with cyanamide for 1 week. The dose of cyanamide was increased up to 150 mg until the patch test yielded a positive result. RESULTS: In the ethanol patch test, 36 alcoholics (25.0%) gave a positive result before treatment with cyanamide and might have been ALDH2(1)/2(2) heterozygotes. Among 108 alcoholics who were not positive, the distribution of the cyanamide dose that yielded a positive ethanol patch test result was 30 mg in 42 cases (38.9%), 50 mg in 33 cases (30.6%), 70 mg in 5 cases (4.6%), 100 mg in 6 cases (5.6%), and 150 mg in 2 cases (1.9%). Prevalence of liver cirrhosis was significantly higher in alcoholics who showed a positive ethanol patch test result at doses of less than 50 mg cyanamide than those at doses more than 70 mg (p = 0.029). The prevalence of adverse effects was significantly higher in alcoholics who showed a positive ethanol patch test result at doses of more than 70 mg than at doses of less than 50 mg cyanamide (p = 0.002). CONCLUSIONS: The ethanol patch test is a useful method for identifying pharmacological effectiveness of cyanamide and may reduce the prevalence of side effects in cyanamide-treated alcoholics.

Adult↗
PubMed2000

Cyanamide-induced liver dysfunction after abstinence in alcoholics: a long-term follow-up study on four cases.

BACKGROUND: Cyanamide, an aversive agent widely used in Japan, is known to induce various degrees of hepatic lesion with ground-glass inclusion bodies. When cyanamide-treated alcoholics relapse into drinking, more severe inflammation develops in the liver. However, it is controversial whether progressive hepatic lesions develop in complete abstainers as a result of long-term cyanamide treatment. CASE REPORTS: Case 1: A 53-year-old male alcoholic received cyanamide treatment for 4.5 months and completely abstained without cyanamide treatment for 6 years. A liver biopsy shortly after abstinence showed extensive pericellular fibrosis, but a biopsy after 6 years showed very mild fibrosis. Case 2: A 43-year-old male alcoholic remained completely abstinent with cyanamide treatment for 5 years and complained of general fatigue. His serum transaminases were slightly elevated and hepatic hyperechogenicity was observed on ultrasonography. Only mild pericellular fibrosis was present in the liver biopsy specimen obtained shortly after abstinence, but after 5 years the second liver biopsy showed that thin septum-like fibrosis that formed portal-to-portal and portal-to-central linkage had developed and ground-glass hepatocytes had emerged extensively. Case 3: A 29-year-old female alcoholic complained of general fatigue and a slight fever after 1.5 years of abstinence with cyanamide treatment. Slight elevation of serum transaminases and hepatic hyperechogenicity were observed. The liver biopsy showed extensive ground-glass hepatocytes and thin septum-like fibrosis that formed portal-to-portal linkage. Case 4: A 61-year-old male alcoholic who remained completely abstinent while taking cyanamide for 3 years showed slight elevation of serum transaminases. Liver biopsy showed extensive ground-glass hepatocytes and extension of thin septum-like fibers from portal tract to the lobule. Ultrasonography revealed hepatic hyperechogenicity. CONCLUSION: In some abstainers who take cyanamide for several years, thin septum-like liver fibrosis progresses along with the emergence of ground-glass hepatocytes. Hepatic hyperechogenicity on ultrasonography and slight elevation of serum transaminases might erroneously lead to a diagnosis of hepatic steatosis without liver histology.

Adult↗
PubMed1991

Urinary excretion of acetylcyanamide in rat and human after oral and dermal application of hydrogen cyanamide (H2NCN).

The main urinary metabolite of hydrogen cyanamide (syn.: cyanamide) in rat and man is acetylcyanamide (syn.: N-acetylcyanamide). An analytical method was developed to determine acetylcyanamide in the urine with a limit of quantification of less than 10 micrograms/l (mean recovery 96.1% using spikes of 20 micrograms/l; relative standard deviation less than 4%). This methodology is based upon ion chromatography using column-switch techniques and UV detection. It could be demonstrated that in rats an average of 45.6% of oral applied cyanamide (10 mg/kg) was excreted in the urine as acetylcyanamide. In male human volunteers a mean of 40% of oral administered cyanamide (mean dose 0.25 mg/kg body weight) was excreted via the urine as acetylcyanamide. The same group of volunteers participated in a skin absorption study with dermal application of the above cyanamide dose onto a skin surface area of 32 cm2. Within an application period of 6 h an average cyanamide quantity of 2.3 mg was available for skin absorption. A mean portion of 7.7% of this quantity was found as acetylcyanamide in the urine of the participants. Findings from literature state that cyanamide is metabolized in vitro to cyanide. According to examinations performed in vivo, however, such a metabolic pathway seems to be irrelevant for man. In comparison with the control values there was no significant increase of both the cyanide concentrations in the blood and the thiocyanate concentrations in the urine of the above volunteers after the described oral cyanamide administration.

Administration, Oral↗
PubMed1999

Cyanamide reduces brain catalase and ethanol-induced locomotor activity: is there a functional link?

The present study was designed in an attempt to assess a previously suggested role of brain catalase activity in ethanol-induced behaviour by examining ethanol-induced locomotor activity in cyanamide-treated mice. Mice were pretreated with IP injections of the catalase inhibitor cyanamide (3.75, 7.5, 15, 30 or 45 mg/kg) or saline. Following this treatment, animals in each group received IP injections of ethanol (0.0, 1.6, 2.4 or 3.2 g/kg) and locomotion was recorded. Several time intervals (0, 5, 10, 15, 20 or 25 h) between the two treatments were also evaluated. Results indicated that cyanamide administration produced a dose-dependent decrease in ethanol-induced locomotor activity that depends on the time between treatments. However, cyanamide did not change spontaneous or d-amphetamine-induced locomotor activity. Moreover, an additive effect of cyanamide and another brain catalase inhibitor, 3-amino-1,2,4-triazole (AT), on the reduction of ethanol-induced locomotor activity was observed. Perfused brain homogenates of mice treated with cyanamide, AT or cyanamide+AT showed a significant reduction of brain catalase activity. The dose and time patterns of both effects were closely related and a significant correlation between them was obtained. These results suggest that cyanamide could reduce locomotor activity through its inhibition of brain catalase, giving further support to the notion that brain catalase may be an important regulator of some ethanol-induced behavioural effects.

Analysis of Variance↗
PubMed1984

Effect of acetaldehyde and cyanamide on the metabolism of formaldehyde by hepatocytes, mitochondria, and soluble supernatant from rat liver.

Formaldehyde can be metabolized primarily by two different pathways, one involving oxidation by the low-Km mitochondrial aldehyde dehydrogenase, the other involving a specific, glutathione-dependent, formaldehyde dehydrogenase. To estimate the roles played by each enzyme in formaldehyde metabolism by rat hepatocytes, experiments with acetaldehyde and cyanamide, a potent inhibitor of the low-Km aldehyde dehydrogenase were carried out. The glutathione-dependent oxidation of formaldehyde by 100,000g rat liver supernatant fractions was not affected by either acetaldehyde or by cyanamide. By contrast, the uptake of formaldehyde by intact mitochondria was inhibited 75 to 90% by cyanamide. Acetaldehyde inhibited the uptake of formaldehyde by mitochondria in a competitive fashion. Formaldehyde was a weak inhibitor of the oxidation of acetaldehyde by mitochondria, suggesting that, relative to formaldehyde, acetaldehyde was a preferred substrate. In isolated hepatocytes, cyanamide, which inhibited the oxidation of acetaldehyde by 75 to 90%, produced only 30 to 50% inhibition of formaldehyde uptake by cells as well as of the production of 14CO2 and of formate from [14C]formaldehyde. The extent of inhibition by cyanamide was the same as that produced by acetaldehyde (30-40%). In the presence of cyanamide, acetaldehyde was no longer inhibitory, suggesting that acetaldehyde and cyanamide may act at the same site(s) and inhibit the same formaldehyde-oxidizing enzyme system. These results suggest that, in rat hepatocytes, formaldehyde is oxidized by cyanamide- and acetaldehyde-sensitive (low-Km aldehyde dehydrogenase) and insensitive (formaldehyde dehydrogenase) reactions, and that both enzymes appear to contribute about equally toward the overall metabolism of formaldehyde.

Acetaldehyde↗
PubMed1989

Inactivation of low-Km rat liver mitochondrial aldehyde dehydrogenase by cyanamide in vitro. A catalase-mediated reaction.

The inactivation of the affinity chromatography purified low-Km rat liver mitochondrial aldehyde dehydrogenase (ALDH)--free of catalase activity--by the alcohol sensitizing agent cyanamide was studied in vitro. This ALDH-purified preparation was not susceptible to cyanamide inactivation at concentrations up to 2.5 mM. On the other hand, ALDH activity appears to be irreversibly inhibited when the incubation mixture contained ALDH, catalase, NAD+ and cyanamide. Influence of catalase, NAD+ and cyanamide concentrations in the incubation mixtures on the ALDH activity were also established. The time course of the concentration of cyanamide in an incubation mixture when ALDH activity was inhibited by cyanamide in the presence of catalase and NAD+, was evaluated by HPLC. No disappearance of cyanamide was observed for a period of time up to 24 hr. This result suggests that no metabolic conversion of cyanamide to an active inhibitory form takes place, as has been suggested recently.

Aldehyde Dehydrogenase↗
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↗
PubMed2006

Quantification of cyanamide contents in herbaceous plants.

Cyanamide (NH2CN) is found in nature, although it has long been recognized as an industrial product. Distribution of cyanamide in the plant kingdom was investigated using a direct quantitative determination method to detect and measure cyanamide by stable isotope dilution gas chromatography-mass spectrometry (the SID-GC-MS method). The SID-GC-MS method proved to be a robust way to quantify cyanamide contents in the extracts of 101 species of herbaceous plants. The average recovery of cyanamide from all plants tested was 55.6+/-20.3%. Vicia villosa and V. cracca contained cyanamide at 369-498 microg/gFW and 3,460-3,579 microg/gFW respectively, while the other 99 species contained no detectable cyanamide (<1 microg/gFW). This result suggests that distribution of cyanamide in the plant kingdom is limited and uneven.

Cyanamide↗
PubMed1989

Effect of cyanamide on transaminases and other serum proteins in the rat.

The changes of the serum biochemical features induced by cyanamide, a drug used in the pharmacological treatment of alcoholism, were studied in Wistar rats. Sixty five Wistar rats were divided into 6 groups, 4 experimental and 2 control. Two experimental groups received cyanamide intraperitoneally, at a dose of 1 and 16 mg per kg of body weight, for 8 weeks. One experimental group received CCl4 and the other one CCl4 and cyanamide for 13 weeks. In addition to a delay in the increase of body weight as compared with the control group, the rats receiving cyanamide underwent a marked dispersion of the transaminase and LDH values. This could be explained by the double effect of cyanamide: its capacity to depress the cellular activity (lowered synthesis of proteins, transaminase and LDH among them) and cellular damage. Therefore, some animals showed a marked depression of protein synthesis, causing low enzyme values while cytolysis prevailed in the rest as seen in higher enzyme values. When cyanamide and CCl4 were employed simultaneously, the cyanamide tended to diminish the higher enzyme values caused by CCl4 when used alone. These findings can explain why patients on cyanamide may develop severe liver damage without serious alterations in tests for liver function.

Alanine Transaminase↗
PubMed2005

Cyanamide-induced aplastic anemia.

OBJECTIVE: To report a case of aplastic anemia in a patient treated with cyanamide, an alcohol-aversive drug. A 67-year-old man was admitted to hospital because of fever and pancytopenia. He had taken cyanamide for 6 months as an alcohol deterrent. No other risk factors for aplastic anemia were identified by interviewing the patient using a structured validated questionnaire. The results of bone-marrow biopsy showed severe aplastic anemia. Cyanamide was discontinued and the patient was treated according to a prespecified treatment protocol. One year after hospital admission, the patient was completely recovered with no need of immunosuppressive therapy. An objective causality assessment revealed that an adverse drug reaction was probable. DISCUSSION: As the efficacy of cyanamide has been questioned, due to the failure of various trials to show any benefit over placebo, its overall benefit/risk ratio should be reconsidered. The complete and rapid hematological recovery after discontinuation of the drug, and the absence of other factors that could explain the condition support the association of the present case of aplastic anemia with cyanamide. The mechanism remains unknown. Aplastic anemia is a rare but potentially serious adverse drug effect of cyanamide treatment. CONCLUSIONS: Given the poor evidence on the efficacy of cyanamide and the associated risk of aplastic anemia, its use in reducing alcohol consumption should be reconsidered.

Aged↗
PubMed1984

The metabolic activation of cyanamide to an inhibitor of aldehyde dehydrogenase is catalyzed by catalase.

The inhibition of aldehyde dehydrogenase by cyanamide is dependent on an enzyme catalyzed conversion of the latter to an active metabolite. The following results suggest that catalase is the enzyme responsible for this bioactivation. The elevation of blood acetaldehyde elicited by cyanamide after ethanol administration to rats was attenuated more than 90 percent by pretreatment with the catalase inhibitor, 3-amino-1,2,4-triazole. This attenuation was dose dependent and was accompanied by a reduction in total hepatic catalase activity. Although hepatic catalase was also inhibited by cyanamide, a positive correlation between blood acetaldehyde and hepatic catalase activity was observed. In vitro, the activation inhibitor, 3-amino-1,2,4-triazole. This attenuation was dose dependent and was accompanied by a reduction in total hepatic catalase activity. Although hepatic catalase was also inhibited by cyanamide, a positive correlation between blood acetaldehyde and hepatic catalase activity was observed. In vitro, the activation of cyanamide was catalyzed by a) the rat liver mitochondrial subcellular fraction, b) the 50-65% ammonium sulfate mitochondrial fraction and c) purified bovine liver catalase. Cyanamide activation was inhibited by sodium azide. Since much of the hepatic catalase is localized in the peroxisomes and since peroxisomes and mitochondria cosediment, the cyanamide activating enzyme, catalase, is likely of peroxisomal and mitochondrial origin.

Acetaldehyde↗