Influence of cardioprotective cyclooxygenase and lipoxygenase inhibitors on peroxidative injury to myocardial-membrane phospholipid

Dr, Janero; Burghardt, Barbara; López, Rocío Gloria Fernández; Cardell, Monika

doi:10.1016/0006-2952(89)90646-1

Cited by 23 publications

(13 citation statements)

References 40 publications

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“…Taken together, our results strongly suggest that the decrease in ROS levels is responsible for attenuating effects of SPZ and 2Cl-SPZ on cardiac reperfusion injury. The sources of ROS generation in cardiac ischemiareperfusion studies are reported to be numerous, including NADPH oxidase (10,11), xanthine oxidase (12), cyclooxygenase (13), lipoxygenase (13), nitric oxide synthase (14,15), mitochondria respiratory chain (16), and CYP (17,18). Of these sources, CYP was chosen as one of the plausible candidates based on our previous studies (17).…”

Section: Discussionmentioning

confidence: 99%

“…A wide variety of potential ROS sources have been reported in cardiac ischemia-reperfusion studies, including NADPH oxidase (10,11), xanthine oxidase (12), cyclooxygenase (13), lipoxygenase (13), nitric oxide synthases (14,15), the mitochondria respiratory chain (16), and cytochrome P450 (CYP) (17,18). We previously reported that intravenous administration of a potent CYP inhibitor, sulfaphenazole (SPZ), at the time of reperfusion reduced myocardial infarct size and improved cardiac function in a rat model of ischemia-reperfusion (17).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Sulfaphenazole Derivatives on Cardiac Ischemia–Reperfusion Injury: Association of Cytochrome P450 Activity and Infarct Size

et al. 2010

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Abstract. Cardiac ischemia-reperfusion injury is evoked by reactive oxygen species (ROS). We previously reported that sulfaphenazole (SPZ) attenuated cardiac ROS levels and ischemia-reperfusion injury in rats. SPZ has distinct two actions: a) elimination of ROS and b) inhibition of cytochrome P450 (CYP) that is responsible for ROS production. The aim of this study is to determine which action contributes to the attenuation of cardiac ischemia-reperfusion injury using SPZ and its derivatives [acetyl-SPZ (Ac-SPZ) and dichloro-SPZ (2Cl-SPZ)]. Administration of 2Cl-SPZ or SPZ prior to ischemia significantly reduced myocardial infarct size, myocardial lipid peroxides, and ROS levels. In addition, they inhibited rat cardiac CYP activity. However, Ac-SPZ neither reduced infarct size nor inhibited cardiac CYP activity. The three compounds had similar effects on ROS scavenging activity in that they scarcely scavenged hydrogen peroxide and superoxide anions but reduced hydroxyl radicals with the same efficacy. The serum concentration of each compound was almost the same until 24 h after reperfusion. Collectively, our findings indicate that the suppressive effects of SPZ and 2Cl-SPZ on ischemia-reperfusion injury are associated with the reduction of ROS levels, which is primarily due to a decrease in ROS production via inhibition of cardiac CYP, not via ROS scavenging activity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Sulfaphenazole Derivatives on Cardiac Ischemia–Reperfusion Injury: Association of Cytochrome P450 Activity and Infarct Size

et al. 2010

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“…It is noteworthy that the concentration-response curve for antiperoxidant inhibition of cardiomyocyte LDH release (Fig. 8) evidenced a steep slope characteristic of processes mediated by lipid peroxidation (Janero et al, 1989).…”

Section: Inhibition Of Lethal Cardiomyocyte Oxidative Injury Induced mentioning

confidence: 99%

Hydrogen peroxide‐induced oxidative stress to the mammalian heart‐muscle cell (cardiomyocyte): Lethal peroxidative membrane injury

Janero¹,

Hreniuk²,

Sharif³

1991

Journal Cellular Physiology

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Oxidative stress induced by hydrogen peroxide (H2O2) may contribute to the pathogenesis of ischemic-reperfusion injury in the heart. For the purpose of investigating directly the injury potential of H2O2 on heart muscle, a cellular model of H2O2-induced myocardial oxidative stress was developed. This model employed primary monolayer cultures of intact, beating neonatal-rat cardiomyocytes and discrete concentrations of reagent H2O2 in defined, supplement-free culture medium. Cardiomyocytes challenged with H2O2 readily metabolized it such that the culture content of H2O2 diminished over time, but was not depleted. The consequent H2O2-induced oxidative stress caused lethal sarcolemmal disruption (as measured by lactate dehydrogenase release), and cardiomyocyte integrity could be preserved by catalase. During oxidative stress, a spectrum of cellular derangements developed, including membrane phospholipid peroxidation, thiol oxidation, consumption of the major chain-breaking membrane antiperoxidant (alpha-tocopherol), and ATP loss. No net change in the protein or phospholipid contents of cardiomyocyte membranes accompanied H2O2-induced oxidative stress, but an increased turnover of these membrane constituents occurred in response to H2O2. Development of lethal cardiomyocyte injury during H2O2-induced oxidative stress did not require the presence of H2O2 itself; a brief "pulse" exposure of the cardiomyocytes to H2O2 was sufficient to incite the pathogenic mechanism leading to cell disruption. Cardiomyocyte disruption was dependent upon an intracellular source of redox-active iron and the iron-dependent transformation of internalized H2O2 into products (e.g., the hydroxyl radical) capable of initiating lipid peroxidation, since iron chelators and hydroxyl-radical scavengers were cytoprotective. The accelerated turnover of cardiomyocyte-membrane protein and phospholipid was inhibited by antiperoxidants, suggesting that the turnover reflected molecular repair of oxidized membrane constitutents. Likewise, the consumption of alpha-tocopherol and the oxidation of cellular thiols appeared to be epiphenomena of peroxidation. Antiperoxidant interventions coordinately abolished both H2O2-induced lipid peroxidation and sarcolemmal disruption, demonstrating that an intimate pathogenic relationship exists between sarcolemmal peroxidation and lethal compromise of cardiomyocyte integrity in response to H2O2-induced oxidative stress. Although sarcolemmal peroxidation was causally related to cardiomyocyte disruption during H2O2-induced oxidative stress, a nonperoxidative route of H2O2 cytotoxicity was also identified, which was expressed in the complete absence of cardiomyocyte-membrane peroxidation. The latter mode of H2O2-induced cardiomyocyte injury involved ATP loss such that membrane peroxidation and cardiomyocyte disruption on the one hand and cellular de-energization on the other could be completely dissociated.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…If there is insufficient enzymatic protection, the presence of catalytically active metal ions will lead to the production of other, highly reactive, mem brane-destructive intermediates, such as hy droxyl radicals [23], Conflicting data have been reported on the possible connection between arachidonic-acid-derived eicosanoid production and reactive oxygen intermediates formed during ischemia-reperfusion. Since cycloox ygenase (and lipoxygenase) can be inhibited by several antioxidants and an increased production of molecular oxygen species may enhance oxygenase activity, an elevation in eicosanoid output and consequently the ef fectiveness of scavengers in limiting post ischemic eicosanoid production could be an ticipated [7,24], Such findings have actually been demonstrated in some experimental models [25,26]. Conversely, the generated oxygen radicals feed back to deactivate the cyclooxygenase, and antioxidant treatment could therefore lead to an enhanced eicosa noid synthesis [6,27], Severe free radical damage can result in major losses of mem brane phospholipids, reducing their avail ability for eicosanoid formation, and thus decreases in the production of 6-keto-PGFia and TxB2 could occur [28].…”

Section: Discussionmentioning

confidence: 99%

Effect of Antioxidant Therapy on Cyclooxygenase-Derived Eicosanoid Release during Intestinal Ischemia-Reperfusion

Boros¹,

Bako

Nagy³

1991

Eur Surg Res

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Conflicting data have been reported on the relationship between reactive oxygen intermediates and the formation of oxygenase-derived eicosanoids. Plasma levels of prostacyclin (PGI₂, measured as the stable metabolite 6-keto-PGF_1α) and thromboxane A₂ (TxA₂, measured as TxA₂) in the effluent blood of a canine ileal segment were determined following 1 or 2 h of ischemia. The synthesis of both eicosanoids was significantly stimulated during reperfusion, but extension of the ischemic interval from 60 to 120 min was not followed by a further increase. The role of oxidants potentially involved in the process was investigated by using materials that inactivate the xanthine-oxidase-generated intermediates. Previous studies on the same in vivo animal model had demonstrated the effectiveness of antioxidant therapy in reducing the postischemic histamine release. There was no significant alteration in the amount of eicosanoids synthesized following oral allopurinol, catalase, dimethylsulfoxide, mannitol or desferrioxamine treatment. Intravenously administered allopurinol, however, significantly elevated the postischemic 6-keto-PGF_1α/TxB₂ ratio. The results suggest that these antioxidants at doses inhibitory to histamine liberation are not effective in influencing the postischemic eicosanoid release. Intravenously administered allopurinol could exert a potentially beneficial effect through a mechanism other than the blockade of xanthine oxidase.

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Influence of cardioprotective cyclooxygenase and lipoxygenase inhibitors on peroxidative injury to myocardial-membrane phospholipid

Cited by 23 publications

References 40 publications

Effects of Sulfaphenazole Derivatives on Cardiac Ischemia–Reperfusion Injury: Association of Cytochrome P450 Activity and Infarct Size

Effects of Sulfaphenazole Derivatives on Cardiac Ischemia–Reperfusion Injury: Association of Cytochrome P450 Activity and Infarct Size

Hydrogen peroxide‐induced oxidative stress to the mammalian heart‐muscle cell (cardiomyocyte): Lethal peroxidative membrane injury

Effect of Antioxidant Therapy on Cyclooxygenase-Derived Eicosanoid Release during Intestinal Ischemia-Reperfusion

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