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Dive into the research topics where Simone Pierpaoli is active.

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Featured researches published by Simone Pierpaoli.


European Journal of Pharmacology | 2002

A role for superoxide in gentamicin-mediated nephropathy in rats

Salvatore Cuzzocrea; Emanuela Mazzon; Laura Dugo; Ivana Serraino; Rosanna Di Paola; Domenico Britti; Angela De Sarro; Simone Pierpaoli; Achille P. Caputi; Emanuela Masini; Daniela Salvemini

Gentamicin is an antibiotic effective against Gram-negative infection, whose clinical use is limited by its nephrotoxicity. Oxygen free radicals are considered to be important mediators of gentamicin-mediated nephrotoxicity, but the exact nature of the radical in question is not known with certainty. We have investigated the potential role of superoxide in gentamicin-induced renal toxicity by using M40403, a low molecular weight synthetic manganese containing superoxide dismutase mimetic, which selectively removes superoxide. Administration of gentamicin at 100 mg/kg, s.c. for 5 days to rats induced a marked renal failure, characterised by a significant decrease in creatinine clearance and increased plasma creatinine levels, fractional excretion of sodium, lithium, urine gamma glutamyl transferase (gamma GT) and daily urine volume. A significant increase in kidney myeloperoxidase activity and lipid peroxidation was also observed in gentamicin-treated rats. M40403 (10 mg/kg, i.p. for 5 days) attenuated all these parameters of damage. Immunohistochemical localisation demonstrated nitrotyrosine formation and poly(ADP-ribose) synthetase (PARS) activation in the proximal tubule of gentamicin-treated rats. Renal histology examination confirmed tubular necrosis. M40403 significantly prevented gentamicin-induced nitrotyrosine formation, poly(ADP-ribose) synthetase activation and tubular necrosis. These results confirm our hypothesis that superoxide anions play an important role in gentamicin-mediated nephropathy and support the possible clinical use of low molecular weight synthetic superoxide dismutase mimetics in those conditions that are associated with over production of superoxide.


Experimental Biology and Medicine | 2003

Heme Oxygenase-1 and the Ischemia-Reperfusion Injury in the Rat Heart

Emanuela Masini; Alfredo Vannacci; Cosimo Marzocca; Simone Pierpaoli; Lucia Giannini; Ornella Fantappiè; Roberto Mazzanti; P. F. Mannaioni

Carbon monoxide (CO) is a signaling gas produced intracellularly by heme oxygenase (HO) enzymes using heme as a substrate. During heme breakdown, HO-1 and HO-2 release CO, biliverdin, and Fe2+. In this study, we investigated the effects of manipulation of the HO-1 system in an in vivo model of focal ischemia–reperfusion (FIR) in the rat heart. Male Wistar albino rats, under general anesthesia and artificial ventilation, underwent thoracotomy, the pericardium was opened, and a silk suture was placed around the left descending coronary artery; ischemia was induced by tightening the suture and was monitored for 30 min. Subsequently, the ligature was released to allow reperfusion lasting for 60 min. The first group of rats was sham operated and injected intraperitoneally (ip) with saline. The second group underwent FIR. The third group was treated ip 18 hr before FIR with hemin (4 mg/kg). The fourth group was pretreated ip 24 hr before FIR and 6 hr before hemin with zinc protoporphyrin IX (ZnPP-IX, 50 μg/kg). Specimens of the left ventricle were taken for determination of HO expression and activity, infarct size, malonyldialdehyde (MDA) production, and tissue calcium content. FIR led to a significant increase in the generation of MDA and notably raised tissue calcium levels. Induction of HO-1 by hemin significantly decreased infarct size, incidence of reperfusion arrhythmias, MDA generation, and calcium overload induced by FIR. These effects were prevented by the HO-1 inhibitor ZnPP-IX. The present experiments show that the concerted actions of CO, iron, and biliverdin/bilirubin modulate the FIR-induced myocardial injury.


European Journal of Pharmacology | 2003

Carbon monoxide modulates the response of human basophils to FcεRI stimulation through the heme oxygenase pathway

Alfredo Vannacci; Roberto Baronti; Giovanni Zagli; Cosimo Marzocca; Simone Pierpaoli; Daniele Bani; Maria Beatrice Passani; Pier Francesco Mannaioni; Emanuela Masini

We report the effects of exogenous and endogenous carbon monoxide (CO) on the immunological activation of human basophils. Hemin (1-100 microM), a heme oxygenase substrate analogue, significantly increased the formation of bilirubin from partially purified human basophils, thus indicating that these cells express heme oxygenase. This effect was reversed by preincubating the cells for 30 min with Zn-protoporphyrin IX (100 microM), a heme oxygenase inhibitor. Hemin (100 microM) also decreased immunoglobulin G anti-Fcepsilon (anti-IgE)-induced activation of basophils, measured by the expression of a membrane granule-associated protein, identified as cluster differentiation protein 63 (CD63), and by histamine release. These effects were reversed by Zn-protoporphyrin IX (100 microM), by oxyhemoglobin (HbO(2)), a CO scavenger (100 microM), and by 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), an inhibitor of the soluble guanylyl cyclase (100 microM). Exposure of basophils to exogenous CO (10 microM for 30 min) also decreased their activation, while nitrogen (N(2)) was ineffective. HbO(2) and ODQ reversed the inhibition, reversing both membrane protein CD63 expression and histamine release to basal values. Both hemin and exogenous CO significantly raised cGMP levels in basophils and blunted the rise of calcium levels caused by immunological activation. This study suggests that CO increases cGMP formation, which in turn induces a fall in intracellular Ca(2+) concentration, thereby resulting in the inhibition of human basophil activation.


Inflammation Research | 2003

Histaminergic receptors modulate the coronary vascular response in isolated guinea pig hearts. Role of nitric oxide.

Simone Pierpaoli; Cosimo Marzocca; Maria Grazia Bello; Walter Schunack; P. F. Mannaioni; Emanuela Masini

AbstractObjective: The effects of histamine and of histamine receptor agonists and antagonists on the coronary outflow and on the generation of nitric oxide (NO) were evaluated on isolated guinea pig hearts. Methods: Isolated guinea pig hearts were perfused for 50 min in a Langendorff apparatus with histamine (10–7– 10–8 M), in the absence or in the presence of NG-monome-thyl-L-arginine (L-NMMA, 10–4 M), a NO synthase inhibitor and of triprolidine (3⋅10–8 M) and cimetidine (10–7 M), H1 receptor and H2 receptor antagonists, and with trifluoromethyl-phenylhistamine (TFMPH, 10–7 M) and dimaprit (10–7 M), H1 and H2 receptor agonists. The effects of (R)-α-methylhistamine (10–7 M), a H3 receptor agonist and of FUB 181 (10–7 M), a H3 receptor antagonist, were studied in the presence of bradykinin (10–7 M). Results: Histamine increases the coronary outflow and the generation of NO in a concentration-dependent fashion. The effects were completely abolished by blocking NO-synthase (NOS) with L-NMMA (10 –4 M). The effects were also abolished by cimetidine (10 –7 M), H 2 receptor antagonist, and only scarcely affected by triprolidine (3⋅10 –8 M), H 1 receptor antagonist. The effects were reproduced by dimaprit (10 –7 M), H 2 receptor agonist, and only scarcely by TFMPH (10 –7 M), a selective H 1 receptor agonist. Bradykinin (10 –7 M) produces a sustained coronary dilation paralleled by a marked increase in the generation of NO; the effects were significantly reduced by L-NMMA. The stimulation of H 3 receptors by (R)-α-methylhistamine (10 –7 M) significantly reduced both effects, which reverted to normal with FUB 181 (10 –7 M), an H 3 receptor antagonist. Conclusion: These results suggest that, in isolated guinea pig hearts, histamine produces coronary dilation through an H 2 /H 3 -dependent mechanism involving the generation of nitric oxide.


Inflammation Research | 2003

1. Histamine in mast cells and basophilsNitric oxide modulates the inhibitory effect of cannabinoids on the immunological activation of guinea pig mast cells

Alfredo Vannacci; Maria Beatrice Passani; Simone Pierpaoli; Lucia Giannini; P. F. Mannaioni; Emanuela Masini

The immunosuppressive effects of Cannabis were first observed in habitual users of its derivatives [1]. The cloning of cannabinoid receptors [2, 3] suggested the possibility of a direct immunosuppressive action of cannabinoids on cells of the immune system, via activation of peripheral CB2 receptors. Moreover, the identification of endogenous cannabinoids implicated that these may modulate the inflammatory responses [4]. These discoveries raised questions about the involvement of the cannabinoid system in maintaining the homeostasis and in the development of some immune system disorders. Accordingly, increasing interest in cannabinoids as potential therapeutic agents developed in recent years. Despite the promising expectations, animal models and in vitro studies on human cells produced contradictory results [5]. We previously demonstrated that activation of CB2 receptors inhibited antigen-stimulated histamine release from sensitised guinea pig mast cells, an effect antagonised by a selective CB2 receptor antagonist [6]. The signalling induced by cannabinoid receptors is extremely complex, as CB receptors activation leads to multiple intracellular cascades. It was recently proposed that the action of cannabinoids on endothelial cells, at least in part, involves regulation of constitutive nitric oxide synthase activity (cNOS) [7]. We here test our hypothesis that CB2-mediated inhibition of guinea pig mast cells immunological activation involves the synthesis of NO.


Archive | 2002

Generation of Nitric Oxide and Carbon Monoxide Provide Protection Against Cardiac Anaphylaxis

Alfredo Vannacci; Cosimo Marzocca; Giovanni Zagli; Simone Pierpaoli; Daniele Bani; Emanuela Masini; Pier Francesco Mannaioni

Cardiac anaphylaxis has been described as the increase in rate and strength of contraction and the onset of arrhythmias in isolated heart preparations from sensitised animals challenged in vitro with specific antigen. These changes in myocardial functions were explained by the release of histamine as the sole mediator,1 or by the combination of histamine release with the production of vasoactive products from the arachidonic acid cascade.2 Cardiac anaphylaxis is widely recognised as an example of type I hypersensitivity in which the release of histamine participates in myocardial damage.2 Endogenous autacoids modulate cardiac anaphylaxis. In the isolated guinea pig heart, catecholamine levels and the availability of catecholamine receptors regulate the release of histamine from sensitised hearts: depletion of catecholamines and the blockade of β-receptors decrease anaphylactic histamine release, which is enhanced by noradrenaline.1 Histamine down-regulates the anaphylactic release of histamine from sensitised guinea pig hearts: H2-receptor agonists decrease the amount of histamine released, whereas cimetidine increases it.3 It has been reported that nitric oxide (NO) modulates cardiac anaphylaxis.4 The NO donor, sodium nitroprusside, decreases anaphylactic histamine release from sensitised guinea pig hearts, which is increased by blocking nitric oxide synthase.4 Relaxin (RLX) is a peptide hormone secreted mainly by the corpus luteum during pregnancy,5 with well established effects on the female reproductive organs. Cardiomyocytes from rat atria have been shown to secrete detectable amounts of RLX suggesting the cardiovascular system as a physiological target.6


Free Radical Biology and Medicine | 2005

Reduction of antigen-induced respiratory abnormalities and airway inflammation in sensitized guinea pigs by a superoxide dismutase mimetic

Emanuela Masini; Daniele Bani; Alfredo Vannacci; Simone Pierpaoli; Pier Francesco Mannaioni; Suzy Comhair; Weiling Xu; Carolina Muscoli; Serpil C. Erzurum; Daniela Salvemini


Journal of Pharmacology and Experimental Therapeutics | 2004

The Endocannabinoid 2-Arachidonylglycerol Decreases the Immunological Activation of Guinea Pig Mast Cells: Involvement of Nitric Oxide and Eicosanoids

Alfredo Vannacci; Lucia Giannini; Maria Beatrice Passani; Annamaria Di Felice; Simone Pierpaoli; Giovanni Zagli; Ornella Fantappiè; Roberto Mazzanti; Emanuela Masini; Pier Francesco Mannaioni


Biochemical and Biophysical Research Communications | 2003

Protective effects of a plant histaminase in myocardial ischaemia and reperfusion injury in vivo.

Emanuela Masini; Simone Pierpaoli; Cosimo Marzocca; Pier Francesco Mannaioni; Paola Pietrangeli; Mircea Alexandru Mateescu; Massimo Zelli; Rodolfo Federico; Bruno Mondovı̀


Inflammation Research | 2003

Nitric oxide modulates the inhibitory effect of cannabinoids on the immunological activation of guinea pig mast cells.

Alfredo Vannacci; Maria Beatrice Passani; Simone Pierpaoli; Lucia Giannini; P. F. Mannaioni; Emanuela Masini

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