A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs

Bianchi, Cesario; Wakiyama, Hidetaka; Faro, Renato; Khan, Tanveer A.; McCully, James D.; Levitsky, Sidney; Szabó, Csaba; Sellke, Frank W.

doi:10.1016/s0003-4975(02)03953-x

Cited by 45 publications

(33 citation statements)

References 25 publications

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“…For instance, FP15 reduced myocardial necrosis in our present rat model of acute myocardial infarction (present study) as well as in a recent porcine study. 45 Furthermore, FP15 significantly improved cardiac function in a diabetic cardiomyopathy model. 21 These observations, coupled with the protective effect of FP 15 against DOX-induced cardiotoxicity reported here, support the concept that peroxynitrite is a major mediator of myocardial injury in various pathophysiological conditions, and its effective neutralization can be of significant therapeutic benefit.…”

Section: Effects Of Fp 15 On Myocardial Damage Produced By Transient mentioning

confidence: 94%

Potent Metalloporphyrin Peroxynitrite Decomposition Catalyst Protects Against the Development of Doxorubicin-Induced Cardiac Dysfunction

et al. 2003

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Background-Increased oxidative stress and dysregulation of nitric oxide have been implicated in the cardiotoxicity of doxorubicin (DOX), a commonly used antitumor agent. Peroxynitrite is a reactive oxidant produced from nitric oxide and superoxide in various forms of cardiac injury. Using a novel metalloporphyrinic peroxynitrite decomposition catalyst, FP15, and nitric oxide synthase inhibitors or knockout mice, we now delineate the pathogenetic role of peroxynitrite in rodent models of DOX-induced cardiac dysfunction. Methods and Results-Mice received a single injection of DOX (25 mg/kg IP). Five days after DOX administration, left ventricular performance was significantly depressed, and high mortality was noted. Treatment with FP15 and an inducible nitric oxide synthase inhibitor, aminoguanidine, reduced DOX-induced mortality and improved cardiac function. Genetic deletion of the inducible nitric oxide synthase gene was also accompanied by better preservation of cardiac performance. In contrast, inhibition of the endothelial isoform of nitric oxide synthase with N-nitro-L-arginine methyl ester increased DOX-induced mortality. FP15 reduced the DOX-induced increase in serum LDH and creatine kinase activities. Furthermore, FP15 prevented the DOX-induced increase in lipid peroxidation, nitrotyrosine formation, and metalloproteinase activation in the heart but not NAD(P)H-driven superoxide generation. Peroxynitrite neutralization did not interfere with the antitumor effect of DOX. FP15 also decreased ischemic injury in rats and improved cardiac function and survival of mice in a chronic model of DOX-induced cardiotoxicity. Conclusions-Thus

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Section: Effects Of Fp 15 On Myocardial Damage Produced By Transient mentioning

confidence: 94%

Potent Metalloporphyrin Peroxynitrite Decomposition Catalyst Protects Against the Development of Doxorubicin-Induced Cardiac Dysfunction

et al. 2003

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“…We and several other groups worked extensively on in vitro and in vivo studies of Fe porphyrins as SOD mimics and ONOO -À scavengers (17,30,45,76,91,126,169,170,184,185,197,211,229,231,232,238,239,309,310,313). The k cat for O 2 ·À dismutation, as well as for ONOO À reduction, is very similar for Fe and Mn analogues (184,185,310) (Table 1).…”

Section: Fe Porphyrinsmentioning

confidence: 99%

“…Ortho isomers of Fe(III) substituted pyridylporphyrins. Groves et al (45,126,197,211,231,232,238,313) synthesized and used in different animal models Fe analogues of ortho quaternized N-pyridylporphyrins as ONOO À scavengers. Two of those have frequently been studied: the triethyleneglycolated FP-15 and the WW-85 that bears pyridyl benzoate substituents (-CH 2 -C 6 H 4 COO À ).…”

Section: Fe Porphyrinsmentioning

confidence: 99%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

471

689

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Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO 3 _ À , peroxyl radical, and less efficiently H 2 O 2 . By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and=or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds. Antioxid. Redox Signal. 13, 877-918.

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“…There are many pathophysiological conditions of the heart that are associated with peroxynitrite formation, including acute myocardial infarction, chronic ischemic heart failure, doxorubicininduced and diabetic cardiomyopathy [86][87][88][89][90][91]. It appears that peroxynitrite decomposition catalysts improve cardiac function and overall outcome in these models.…”

Section: Peroxynitrite Neutralization Improves Cardiac and Vascular Dmentioning

confidence: 99%

Role of Nitrosative Stress and Peroxynitrite in the Pathogenesis of Diabetic Complications. Emerging New Therapeutical Strategies

Pacher

Obrosova

Mabley

et al. 2005

CMC

308

243

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Macro-and microvascular disease are the most common causes of morbidity and mortality in patients with diabetes mellitus. Diabetic cardiovascular dysfunction represents a problem of great clinical importance underlying the development of various severe complications including retinopathy, nephropathy, neuropathy and increase the risk of stroke, hypertension and myocardial infarction. Hyperglycemic episodes, which complicate even well-controlled cases of diabetes, are closely associated with increased oxidative and nitrosative stress, which can trigger the development of diabetic complications. Hyperglycemia stimulates the production of advanced glycosylated end products, activates protein kinase C, and enhances the polyol pathway leading to increased superoxide anion formation. Superoxide anion interacts with nitric oxide, forming the potent cytotoxin peroxynitrite, which attacks various biomolecules in the vascular endothelium, vascular smooth muscle and myocardium, leading to cardiovascular dysfunction. The pathogenetic role of nitrosative stress and peroxynitrite, and downstream mechanisms including poly(ADP-ribose) polymerase (PARP) activation, is not limited to the diabetes-induced cardiovascular dysfunction, but also contributes to the development and progression of diabetic nephropathy, retinopathy and neuropathy. Accordingly, neutralization of peroxynitrite or pharmacological inhibition of PARP is a promising new approach in the therapy and prevention of diabetic complications. This review focuses on the role of nitrosative stress and downstream mechanisms including activation of PARP in diabetic complications and on novel emerging therapeutical strategies offered by neutralization of peroxynitrite and inhibition of PARP.

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A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs

Cited by 45 publications

References 25 publications

Potent Metalloporphyrin Peroxynitrite Decomposition Catalyst Protects Against the Development of Doxorubicin-Induced Cardiac Dysfunction

Potent Metalloporphyrin Peroxynitrite Decomposition Catalyst Protects Against the Development of Doxorubicin-Induced Cardiac Dysfunction

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Role of Nitrosative Stress and Peroxynitrite in the Pathogenesis of Diabetic Complications. Emerging New Therapeutical Strategies

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