NADPH- and NADH-dependent oxygen radical generation by rat liver nuclei in the presence of redox cycling agents and iron

Kukielka, E.; Cederbaum, Arthur I.

doi:10.1016/0003-9861(90)90650-n

Cited by 25 publications

(14 citation statements)

References 44 publications

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“…These observations indicate that cardiac lipid peroxidation proceeds via reactive intermediates that must be different from hydroxyl radical, as the formation of this species would be favored, rather than inhibited, by H 2 O 2 (8). In this setting, Minotti and Aust (32,33,64) and several other research groups (65)(66)(67)(68)(69)(70) have proposed that the hydroxyl radical cannot promote lipid peroxidation, inasmuch as it exhibits a diffusion-limited reactivity and cannot migrate from the site(s) of generation to the hydrophobic membrane phases where the bis-allylic bonds are buried. Lipid peroxidation would occur anytime iron oxidizes incompletely to the ferric form, yielding perferryl ions [Fe(II)O 2 -Fe(III) ] or oxygen-bridged Fe(II)-Fe(III) complexes that are more stable and can substitute for hydroxyl radical (33,(64)(65)(66)(67).…”

Section: Discussionmentioning

confidence: 91%

Paradoxical inhibition of cardiac lipid peroxidation in cancer patients treated with doxorubicin. Pharmacologic and molecular reappraisal of anthracycline cardiotoxicity.

et al. 1996

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Anticancer therapy with doxorubicin (DOX) and other quinone anthracyclines is limited by severe cardiotoxicity, reportedly because semiquinone metabolites delocalize Fe(II) from ferritin and generate hydrogen peroxide, thereby promoting hydroxyl radical formation and lipid peroxidation. Cardioprotective interventions with antioxidants or chelators have nevertheless produced conflicting results. To investigate the role and mechanism(s) of cardiac lipid peroxidation in a clinical setting, we measured lipid conjugated dienes (CD) and hydroperoxides in blood plasma samples from the coronary sinus and femoral artery of nine cancer patients undergoing intravenous treatments with DOX. Before treatment, CD were unexpectedly higher in coronary sinus than in femoral artery (342 Ϯ 131 vs 112 Ϯ 44 nmol/ml, mean Ϯ SD; P Ͻ 0.01), showing that cardiac tissues were spontaneously involved in lipid peroxidation. This was not observed in ten patients undergoing cardiac catheterization for the diagnosis of arrhythmias or valvular dysfunctions, indicating that myocardial lipid peroxidation was specifically increased by the presence of cancer. The infusion of a standard dose of 60 mg DOX/m 2 rapidly ( ‫ف‬ 5 min) abolished the difference in CD levels between coronary sinus and femoral artery (134 Ϯ 95 vs 112 Ϯ 37 nmol/ml); moreover, dose fractionation studies showed that cardiac release of CD and hydroperoxides decreased by ‫ف‬ 80% in response to the infusion of as little as 13 mg DOX/m 2 . Thus, DOX appeared to inhibit cardiac lipid peroxidation in a rather potent manner. Corollary in vitro experiments were performed using myocardial biopsies from patients undergoing aortocoronary bypass grafting. These experiments suggested that the spontaneous exacerbation of lipid peroxidation probably involved preexisting Fe(II) complexes, which could not be sequestered adequately by cardiac isoferritins and became redox inactive when hydrogen peroxide was included to simulate DOX metabolism and hydroxyl radical formation.

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Section: Discussionmentioning

confidence: 91%

Paradoxical inhibition of cardiac lipid peroxidation in cancer patients treated with doxorubicin. Pharmacologic and molecular reappraisal of anthracycline cardiotoxicity.

et al. 1996

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“…CYP2E1, for example, has been shown in microsomal studies to generate oxidants and lipid peroxidation by-products following treatment of rats with either ingestion of ethanol or exposure to a 95% oxygen atmosphere (16,17,19,23). Generation of superoxide, hydrogen peroxide, and hydroxyl radical has been shown in vitro using reconstituted membrane vesicle systems with purified CYP1A2, CYP2B4, or CYP2E1 enzymes (18,20,21,24). In vivo studies suggest indirectly the possible involvement of CYP in oxidative damage to DNA as an increase in 8-oxo-2'-deoxyguanosine (oxo8dG) production observed upon treatment of rats with agents (i.e., peroxisome proliferators, phenobarbital) that are known to result in, among other effects, an associated elevation in CYP2B or CYP4 activity (25,26).…”

mentioning

confidence: 99%

Induction of cytochrome P4501A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin or indolo(3,2-b)carbazole is associated with oxidative DNA damage.

Park

Shigenaga

Ames

1996

Proc. Natl. Acad. Sci. U.S.A.

229

120

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Induction of cytochrome P4501A1 (CYPlA1) in the hepatoma Hepalclc7 cell line results in an elevation in the excretion rate of 8-oxoguanine (oxo8Gua), a biomarker of oxidative DNA damage and the major repair product of 8-oxo-2'-deoxyguanosine (oxo8dG) residues in DNA. Treatment of this cell line with 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD), a nonmetabolized environmental contaminant, and indolo(3,2-b)carbazole (ICZ), a metabolite of a natural pesticide found in cruciferous vegetables, is shown to both induce CYPlAl activity and elevate the excretion rate of oxo8Gua; 7,8-benzoflavone (7,8-BF or ai-naphthoflavone), an inhibitor of CYPlAl activity and an antagonist of the aryl hydrocarbon (Ah) receptor, reduced the excretion rate of oxo8Gua. The essential role of Ah-receptor, which mediates the induction of CYPlAl, is shown by the inability of TCDD to induce CYPlAl and to increase excretion of oxo8Gua in Ah receptor-defective c4 mutant cells. While there was a significant 7.0-fold increase over 2 days in the excretion rate of oxo8Gua into the growth medium of TCDD-treated Hepalclc7 cells compared to control, no significant increase was detected in the steady-state level of oxo8dG in the DNA presumably due to efficient DNA repair. Thus, the induction of CYPlAl appears to lead to a leak ofoxygen radicals and consequent oxidative DNA damage that could lead to mutation and cancer.Cytochrome P450 (CYP) is a family of enzymes involved in the oxidative metabolism of both synthetic and natural compounds (1, 2). Humans are exposed to many CYP inducers (3-6) from eating plant chemicals such as indolo(3,2-b)carbazole (ICZ), from broccoli and other cruciferous vegetables (5), and also from environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It is possible that the carcinogenic effects of TCDD (7,8) and phenobarbital (9) may, in part, reside in the capacity of the induced CYP enzymes to leak oxidants and thus promote cell division (10) and oxidative DNA damage.The mechanisms of CYPlAl induction by TCDD (11-13) and its involvement in the metabolism of xenobiotics (4, 14, 15) has been investigated extensively. The CYP catalytic cycle involves binding of the substrate followed by binding and activation of molecular oxygen to a reactive intermediate, which hydroxylates the substrate. Most studies designed to investigate the toxicological consequences of CYP induction have been directed toward understanding pathways by which substrate molecules are bioactivated to reactive and genotoxic compounds. The formation of hydrogen peroxide and water as end products of CYP catalysis has been well described (16-21), but the biological consequences of this oxidant leakage from CYP in vivo has received relatively little attention. A postulated mechanism of production of activated 02 is the autoxidation of the oxycytochrome P450 complex, generating superThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance...

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“…To explain these high • OH concentrations in placental and fetal tissues observed in the rat and expected in the other species (actually reported in pathological states), H 2 O 2 could diffuse across the membranes and react with redox minerals (mainly Fe) in the cytoplasma [44], at the level of the nuclear membrane [43] or within the nucleus [45]. Direct formation of O −• 2 production at the level of the nuclear membrane through an NAD(P)H dependent mechanism is possibly of major importance and can end in the interaction of this radical with iron to produce • OH [43]. More means of • OH formation can be recruited, such as interactions between H 2 O 2 or O −• 2 and iron [17] or interactions between various peroxides of proteins, lipids or catechols and redox minerals [2,10,42,46].…”

Section: Origin Of Ros Production During Gestationmentioning

confidence: 89%

“…ROS can also be formed after electron escape from the mitochondria of proliferating cells, favored by high rates of multiplication and metabolism and increased activity of mitochondrial superoxide dismutase (Mn-SOD) [39,40] or, in human placental mitochondria, after interaction between NADPH and iron [41]. Other sources of ROS are increased activities of NADPH oxidases by contact between tissues from the embryo and mother or between replicating cells [33], interactions between estrogens and minerals [42] or triggering of NADPH peroxidases associated to the membranes inside the cells [43].…”

Section: Origin Of Ros Production During Gestationmentioning

confidence: 99%

“…In those instances, high rates of storage of iron occur in the placenta and in the fetus observed in various species including the bovine, starting from the early stages of pregnancy [47] and can be released through many different mechanisms [48]. The • OH radical seems essential in several pathways of signal transduction, although it also induces risks of severe oxidative stress [42,43,49].…”

Section: Origin Of Ros Production During Gestationmentioning

confidence: 99%

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Gestation linked radical oxygen species fluxes and vitamins and trace mineral deficiencies in the ruminant

2006

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-In mammals, radical oxygen species (ROS) are essential factors of cell replication, differentiation and growth (oxidative signal), notably during gestation, but are also potentially damaging agents. In Women, ROS play a role in remodeling of uterine tissues, implantation of the embryo, settlement of the villi and development of blood vessels characteristic of gestation. The body stores of vitamins and minerals of gestating females are used to keep ROS fluxes at a level corresponding to oxidative signals and to prevent an imbalance between their production and scavenging (oxidative stress), which would be detrimental to the mother and fetus. There is some evidence that, although based on different regulatory mechanisms, most of the effects of ROS reported in humans also occur in pregnant ruminant females, some of which have been actually reported. Many vitamins and trace elements have dual effects in the organism of mammals: (a) they are involved in the control of metabolic pathways or/and gene expression, (b) but most of the time they also display ROS trapping activity or their deficiencies induce high rates of ROS production. Deficiencies induce different disorders of gestation and can be induced by different kinds of stress. An example is given, corresponding to the decreased contents of cobalt of forages, when exposed to sustained heavy rains, so that the supply of vitamins B12 to the organism of the ruminant that grazes them is reduced and failure of gestation is induced. Outdoor exposure of ruminants to adverse climatic conditions by itself can increase the vitamin and trace element requirements. Adaptation of production systems taking into account these interactions between gestation and sources of stress or change of the quality of feeding stuffs as well as further developments of knowledge in that field is necessary to promote sustainable agricultural practices.gestation / ovine / bovine / vitamins / trace elements / antioxidant enzymes / radical oxygen species / radical phenomena

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NADPH- and NADH-dependent oxygen radical generation by rat liver nuclei in the presence of redox cycling agents and iron

Cited by 25 publications

References 44 publications

Paradoxical inhibition of cardiac lipid peroxidation in cancer patients treated with doxorubicin. Pharmacologic and molecular reappraisal of anthracycline cardiotoxicity.

Paradoxical inhibition of cardiac lipid peroxidation in cancer patients treated with doxorubicin. Pharmacologic and molecular reappraisal of anthracycline cardiotoxicity.

Induction of cytochrome P4501A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin or indolo(3,2-b)carbazole is associated with oxidative DNA damage.

Gestation linked radical oxygen species fluxes and vitamins and trace mineral deficiencies in the ruminant

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