Generation of superoxide anion as a source of hydrogen peroxide in a reconstituted monooxygenase system

Kuthan, Hartmut; Tsuji, Hiroshi; Graf, Hermann; Ullrich, Volker; Werringloer, J.; Estabrook, Ronald W.

doi:10.1016/0014-5793(78)81206-x

Cited by 148 publications

(39 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thereby, a ratio of 0; to H202 close to 2: 1 is obtained. This result is in agreement with our former quantifications of 0; radicals generated in the reconstituted and microsomal cytochrome P450 system using xanthine oxidase/xanthine standards of 0 2 production for the calibration [12,15].…”

Section: Stoichiometry Of 0: and H202 Formationsupporting

confidence: 92%

“…In previous experiments with a reconstituted monooxygenase system we could show that hydrogen peroxide was formed by a dismutation of free superoxide radicals generated by cytochrome P450 [12]. As was later confirmed by Ingelman-Sundberg et al [13], these radicals were probably released by decomposition of oxygenated cytochrome P450.…”

Section: Abbreviation Hepes 4-(2-hydroxyethyl)-l-piperazineethanesumentioning

confidence: 52%

“…Partially succinoylated ferricytochrome c in combination with superoxide dismutase was used for the detection of 0; radicals as reported previously [12,14]. The reduction of the succinoylated ferricytochrome c was monitored in an Aminco DW-2 spectrophotometer using the wavelength pair 550 nm minus 557 nm.…”

Section: Test For Superoxide Anion Radicalsmentioning

confidence: 99%

See 2 more Smart Citations

Oxidase and Oxygenase Function of the Microsomal Cytochrome P450 Monooxygenase System

Kuthan

Ullrich

1982

European Journal of Biochemistry

Self Cite

191

View full text Add to dashboard Cite

The rates of the NADPH-dependent formation of superoxide radicals and hydrogen peroxide have been measured in liver microsomes from phenobarbital-pretreated rats. Correcting a quenching of 0; radicals by microsomes, a stoichiometry of 0; to Hz02 close to 2 : 1 was obtained. This, and the fact that pseudo-substrates of microsomal cytochrome P450 like perfluoro-n-hexane and perfluorinated cyclohexane did not increase H2Oz formation in a catalase-inhibited assay, rules out a two-electron reduced oxygen species as the source of HzO2.The rates of 0; as well as HzO2 generation in the presence of 7-ethoxycoumarin were equally inhibited by carbon monoxide (75%) and resulted in photochemical action spectra with a maximum reactivation at 450 nm. Using the same conditions the monooxygenation was inhibited to a high degree (83%) but without exogenous substrate the inhibition of H202 formation dropped to 55 "/,.It was concluded that most of the 0; originated from the oxycomplex of cytochrome P450 and that substrates can modify the rates of its decomposition and sensitivity to carbon monoxide. No correlation of H202 formation or of substrate monooxygenation with the optical substrate binding spectra could be observed. From the pH dependence a proton-assisted decomposition of oxy-cytochrome P450 appears likely. H202 formation was only slightly decreased at 20 pM dioxygen suggesting that H202 formation via cytochrome P450 should also occur in vivo.After the early observation by Gillette et al. [I] it was confirmed repeatedly that liver microsomes generate hydrogen peroxide during the oxidation of NADPH [2-41. The reaction seemed to be linked to the monooxygenation system for xenobiotics, since pretreatment of the animals with phenobarbital or pregnenolone-l6a-carbonitrile increased the rate of H202 formation [3], and inhibitors of cytochrome P450 affected the production of H202 and the N-demethylation of ethylmorphine in a similar fashion [4]. However, the underlying mechanisms of hydrogen peroxide formation are not well understood [5]. It was found that some substrates of the monooxygenase system stimulate Hz02 formation whereas others are either not effective or are effective only in animals pretreated with phenobarbital but not with pregnenolone16a-carbonitrile [3,4]. A correlation of H202 formation with the spectral binding and hydroxylation of hexobarbital was observed by Heinemeyer et al. [6] from which a hypothetical peroxide complex of cytochrome P450 was postulated as a common intermediate for Hz02 formation and substrate hydroxylation.If this hypothesis is correct, an increased H202 formation should be observable upon addition of pseudo-substrates [7,8] of the microsomal cytochrome P450 monooxygenase system. This was reinvestigated in the present study.As a second possible pathway of NADPH-dependent formation of H202 in liver microsomes the release of superoxide anion radicals by autoxidation of microsomal redox systems, and the subsequent disproportionation of these Saarland, Homburg-Saar, Federal Republic of German...

show abstract

Section: Stoichiometry Of 0: and H202 Formationsupporting

confidence: 92%

Section: Abbreviation Hepes 4-(2-hydroxyethyl)-l-piperazineethanesumentioning

confidence: 52%

See 1 more Smart Citation

Oxidase and Oxygenase Function of the Microsomal Cytochrome P450 Monooxygenase System

Kuthan

Ullrich

1982

European Journal of Biochemistry

Self Cite

191

View full text Add to dashboard Cite

show abstract

“…Both H202 and OT• were released by microsomes incubated with TCB+NADPH. SOD abolished HE oxidation, indicating that there was release of OT• following addition of one electron, as shown for other CYP (Kuthan et al, 1978). H202 could result either from dismutation of 02-· or from direct formation after addition of a second electron.…”

Section: Discussionmentioning

confidence: 55%

Involvement of Cytochrome P450 1A in the toxicity of aryl hydrocarbon receptor agonists : alteration arachidonic acid metabolism and production of reactive oxygen species

Schlezinger¹

1998

View full text Add to dashboard Cite

“…The one electron oxidation of APAP by CYPs may generate reactive oxygen species (ROS). Hydrogen peroxide and superoxide are produced during metabolic activation of APAP in the mixed function oxidase system [31,32,33].…”

Section: Determination Of the Enzymatic Activity Of Antioxidantsmentioning

confidence: 99%

Evaluation of Acetaminophen Effect on Oxidative Stressed Mice by Peroxide Hydrogen

Zoubair¹,

Azzahra²,

Hmimid³

et al. 2013

AJBR

View full text Add to dashboard Cite

Acetaminophen (Paracetamol) is among the most commonly used analgesic and antipyretic drugs worldwide, it's often, but anomalously, classified as non-steroidal anti-inflammatory drugs (NSAIDs) in textbooks of pharmacology [1,2]. This study aims to evaluate if paracetamol has an antioxidant effect, relative to its analgesic antipyretic and weak anti-inflammatory activities, or it possesses a cytotoxic potential. Oxidative stress was induced by intraperetoneal injection of peroxide hydrogen (H 2 O 2 ), and then a comparative study is made concerning the activities of the antioxidant enzymes SOD, CAT, and GR as well as lipid peroxidation levels in liver. An increase in SOD, CAT, GR activity and lipid peroxidation in mice treated with H 2 O 2 accompanied by paracetamol; compared to the group treated by vitamin C + H 2 O 2 showed that acetaminophen doesn't show any antioxidant effect. Moreover this study has suggested that acetaminophen induced cytotoxicity in liver mediated by increased oxidative stress and altered redox metabolism. Keywords: acetaminophen (paracetamol), peroxide hydrogen, oxidative stressCite This Article: BENKHASSI Zoubair, LAHLOU Fatima Azzahra, HMIMID Fouzia, LOUTFI Mohammed, BENAJI Brahim, and BOURHIM Noureddine, "Evaluation of Acetaminophen Effect on Oxidative Stressed Mice by Peroxide Hydrogen

show abstract

Generation of superoxide anion as a source of hydrogen peroxide in a reconstituted monooxygenase system

Cited by 148 publications

References 17 publications

Oxidase and Oxygenase Function of the Microsomal Cytochrome P450 Monooxygenase System

Oxidase and Oxygenase Function of the Microsomal Cytochrome P450 Monooxygenase System

Involvement of Cytochrome P450 1A in the toxicity of aryl hydrocarbon receptor agonists : alteration arachidonic acid metabolism and production of reactive oxygen species

Evaluation of Acetaminophen Effect on Oxidative Stressed Mice by Peroxide Hydrogen

Contact Info

Product

Resources

About