Daniele Mancardi - Academia.edu (original) (raw)

Papers by Daniele Mancardi

Antioxidants

Donors of nitroxyl (HNO), the one electron-reduction product of nitric oxide (NO.), positively mo... more Donors of nitroxyl (HNO), the one electron-reduction product of nitric oxide (NO.), positively modulate cardiac contractility/relaxation while limiting ischemia-reperfusion (I/R) injury. The mechanisms underpinning HNO anti-ischemic effects remain poorly understood. Using isolated perfused rat hearts subjected to 30 min global ischemia/1 or 2 h reperfusion, here we tested whether, in analogy to NO., HNO protection requires PKCε translocation to mitochondria and KATP channels activation. To this end, we compared the benefits afforded by ischemic preconditioning (IPC; 3 cycles of I/R) with those eventually granted by the NO. donor, diethylamine/NO, DEA/NO, and two chemically unrelated HNO donors: Angeli’s salt (AS, a prototypic donor) and isopropylamine/NO (IPA/NO, a new HNO releaser). All donors were given for 19 min before I/R injury. In control I/R hearts (1 h reperfusion), infarct size (IS) measured via tetrazolium salt staining was 66 ± 5.5% of the area at risk. Both AS and IPA/N...

Meter = 6 mm). Magnification 10×.<b>Copyright information:</b>Taken from "Fracta... more Meter = 6 mm). Magnification 10×.<b>Copyright information:</b>Taken from "Fractal parameters and vascular networks: facts & artifacts"http://www.tbiomed.com/content/5/1/12Theoretical Biology & Medical Modelling 2008;5():12-12.Published online 17 Jul 2008PMCID:PMC2490683.

Canadian Journal of Physiology and Pharmacology

Pancreatic carcinoma incidence showed a significant increase in men over the last few years and t... more Pancreatic carcinoma incidence showed a significant increase in men over the last few years and the prognosis remains poor. Patients are treated with different pharmacological plans with no evidence about gender-specific adverse effects. We aimed to investigate differences in the incidence of chemotherapy side effects in the treatment of pancreatic cancer, in order to provide insights toward a personalized assistance based in individual needs. The sample population is composed of 207 patients. Regression model highlighted the predictive role of female gender for alopecia, constipation, hand-foot syndrome and epigastric pain. Also considering single therapeutic schemes, gender differences have been reported. Moreover, evaluating the effect of age, a general reduced risk of toxicity has been reported in younger patients. In order to personalize chemotherapy and increase patients survival rate and life quality during the therapy, gender medicine and pharmacology studies are recommended.

Oxidative Medicine and Cellular Longevity

Endothelial cell injury and vascular function strongly correlate with cardiac function following ... more Endothelial cell injury and vascular function strongly correlate with cardiac function following ischemia/reperfusion injury. Several studies indicate that endothelial cells are more sensitive to ischemia/reperfusion compared to cardiomyocytes and are critical mediators of cardiac ischemia/reperfusion injury. H2S is involved in the regulation of cardiovascular system homeostasis and can act as a cytoprotectant during ischemia/reperfusion. Activation of ERK1/2 in endothelial cells after H2S stimulation exerts an enhancement of angiogenesis while its inhibition significantly decreases H2S cardioprotective effects. In this work, we investigated how H2S pretreatment for 24 hours prevents the ischemia/reperfusion injury and promotes angiogenesis on microvascular endothelial cells following an ischemia/reperfusion protocol in vitro, using a hypoxic chamber and ischemic buffer to simulate the ischemic event. H2S preconditioning positively affected cell viability and significantly increased...

Redox Biology

Background: endothelial cells play a key role in vessels formation both under physiological and p... more Background: endothelial cells play a key role in vessels formation both under physiological and pathological conditions. Their behavior is influenced by blood components including gasotransmitters (H 2 S, NO and CO). Tumor cells are subjected to a cyclic shift between pro-oxidative and hypoxic state and, in this scenario, H 2 S can be both cytoprotective and detrimental depending on its concentration. H 2 S effects on tumors onset and development is scarcely studied, particularly concerning tumor angiogenesis. We previously demonstrated that H 2 S is proangiogenic for tumoral but not for normal endothelium and this may represent a target for antiangiogenic therapeutical strategies. Methods: in this work, we investigate cell viability, migration and tubulogenesis on human EC derived from two different tumors, breast and renal carcinoma (BTEC and RTEC), compared to normal microvascular endothelium (HMEC) under oxidative stress, hypoxia and treatment with exogenous H 2 S. Results: all EC types are similarly sensitive to oxidative stress induced by hydrogen peroxide; chemical hypoxia differentially affects endothelial viability, that results unaltered by real hypoxia. H 2 S neither affects cell viability nor prevents hypoxia and H 2 O 2-induced damage. Endothelial migration is enhanced by hypoxia, while tubulogenesis is inhibited for all EC types. H 2 S acts differentially on EC migration and tubulogenesis. Conclusions: these data provide evidence for a great variability of normal and altered endothelium in response to the environmental conditions.

Oxidative Medicine and Cellular Longevity, 2016

The prevalence of heart failure (HF) is still increasing worldwide, with enormous human, social, ... more The prevalence of heart failure (HF) is still increasing worldwide, with enormous human, social, and economic costs, in spite of huge efforts in understanding pathogenetic mechanisms and in developing effective therapies that have transformed this syndrome into a chronic disease. Myocardial redox imbalance is a hallmark of this syndrome, since excessive reactive oxygen and nitrogen species can behave as signaling molecules in the pathogenesis of hypertrophy and heart failure, leading to dysregulation of cellular calcium handling, of the contractile machinery, of myocardial energetics and metabolism, and of extracellular matrix deposition. Recently, following new interesting advances in understanding myocardial ROS and RNS signaling pathways, new promising therapeutical approaches with antioxidant properties are being developed, keeping in mind that scavenging ROS and RNStout courtis detrimental as well, since these molecules also play a role in physiological myocardial homeostasis.

Sport Sciences for Health, 2015

Anyone can freely access the full text of works made available as "Open Access". Works made avail... more Anyone can freely access the full text of works made available as "Open Access". Works made available under a Creative Commons license can be used according to the terms and conditions of said license. Use of all other works requires consent of the right holder (author or publisher) if not exempted from copyright protection by the applicable law.

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2008

Beta(2)-adrenoreceptor overexpression is beneficial against ischemia/reperfusion (I/R) injury. Wh... more Beta(2)-adrenoreceptor overexpression is beneficial against ischemia/reperfusion (I/R) injury. Whether beta-adrenoreceptors are involved in postconditioning (PostC) is unknown. We investigated whether nandrolone-decanoate (ND)-pretreatment can modulate (1) beta-adrenoreceptor expression and (2) post-ischemic cardiac function in response to I/R and PostC. Finally, we tested whether cardioprotection can be prevented by the inhibition of beta(2)-adrenoreceptors. Isolated rat hearts from ND pretreated (15 mg/kg/day i.m., for 14 days) and untreated-animals underwent 30-min ischemia and 120-min reperfusion. In subgroups, at the end of ischemia a PostC protocol (five cycles of 10-s reperfusion and 10-s ischemia) was applied and/or a beta(2)-adrenoreceptor blocker, ICI-118.551 (10 microM), was infused. Left ventricular pressure (LVP) was measured with an electromanometer, and infarct-size was evaluated using nitro-blue-tetrazolium staining. ND-pretreatment increased beta(2)-adrenoreceptor e...

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2008

Endogenous platelet activating factor (PAF) is involved in heart ischemic preconditioning. PAF ca... more Endogenous platelet activating factor (PAF) is involved in heart ischemic preconditioning. PAF can also afford pharmacological preconditioning. We studied whether mitochondrial-ATP-sensitive K(+) (mK(ATP)) channels and reactive oxygen species (ROS) are involved in PAF-induced cardioprotection. In Group 1 control hearts, Langendorff-perfused rat hearts underwent 30 min ischemia and 2 hours of reperfusion. Group 2 hearts, before ischemia, were perfused for 19 min with PAF (2x10(-11) M); Groups 3 and 4 hearts were co-infused with PAF and N-acetyl-L-cysteine or 5-hydroxydecanoate to scavenge ROS or to block mK(ATP) channels, respectively. Left ventricular pressure and infarct size were determined. PAF-pretreatment reduced infarct size (33 +/- 4% vs 64 +/- 4.6 % of the area at risk of control hearts) and improved pressure recovery. Infarct-sparing effect of PAF was abolished by N-acetyl-L-cysteine and 5-hydroxydecanoate. Thus, the cardioprotective effect exerted by PAF-pretreatment invol...

Progress in Inorganic Chemistry, 2005

Life Sciences, 2005

Ischemic preconditioning (IP) triggers cardioprotection via a signaling pathway that converges on... more Ischemic preconditioning (IP) triggers cardioprotection via a signaling pathway that converges on mitochondria. The effects of the inhibition of carnitine palmitoyltransferase I (CPT-I), a key enzyme for transport of long chain fatty acids (LCFA) into the mitochondria, on ischemia/reperfusion (I/R) injury are unknown. Here we investigated, in isolated perfused rat hearts, whether sub-chronic CPT-I inhibition (5 days i.p. injection of 25 mg/kg/day of Etomoxir) affects I/R-induced damages and whether cardioprotection by IP can be induced after this inhibition. Effects of global ischemia (30 min) and reperfusion (120 min) were examined in hearts harvested from Control (untreated), Vehicle- or Etomoxir-treated animals. In subsets of hearts from the three treated groups, IP was induced by three cycles of 3 min ischemia followed by 10 min reperfusion prior to I/R. The extent of I/R injury under each condition was assessed by changes in infarct size as well as in myocardial contractility. Postischemic contractility, as indexed by developed pressure and dP/dt(max), was similarly affected by I/R, and was similarly improved with IP in Control, Vehicle or Etomoxir treated animals. Infarct size was also similar in the three subsets without IP, and was significantly reduced by IP regardless of CPT-I inhibition. We conclude that CPT-I inhibition does not affect I/R damages. Our data also show that IP affords myocardial protection in CPT-I inhibited hearts to a degree similar to untreated animals, suggesting that a long-term treatment with the metabolic anti-ischemic agent Etomoxir does not impede the possibility to afford cardioprotection by ischemic preconditioning.

Current Pharmaceutical Biotechnology, 2011

Hydrogen sulphide (H2S) is a recently discovered gasotransmitter that may regulate a growing numb... more Hydrogen sulphide (H2S) is a recently discovered gasotransmitter that may regulate a growing number of endothelial functions, including nitric oxide (NO) release, proliferation, adhesion and migration, which are the key steps of angiogenesis. The mechanism whereby H2S impacts on endothelial physiology is still unclear: however, the aforementioned processes are driven by an increase in intracellular Ca2+ concentration ([Ca2+]i). In the present study, we exploited the excised rat aorta to gain insights into the regulation of [Ca2+]i by H2S within in situ endothelial cells (ECs). Sodium hydrosulphide (NaHS), a H2S donor, caused an elevation in [Ca2+]i, which disappeared in absence of extracellular Ca2+. NaHSinduced Ca2+ inflow was sensitive to high doses of Gd3+, but not BTP-2. Inhibition of the reverse-mode of the Na+-Ca2+ exchanger (NCX), with KB-R7943 or upon removal of extracellular Na+, abrogated the Ca2+ response to NaHS. Moreover, NaHS-elicited Ca2+ entry was significantly reduced by TEA and glybenclamide, which hinted at the involvement of ATP-dependent K+ (KATP) channels. Conversely, NaHS-evoked Ca2+ signal was not affected by the reducing agent, dithiothreitol. Acute addition of NaHS hindered both Ca2+ release and Ca2+ entry induced by ATP, a physiological agonist of ECs. Consistently, inhibition of endogenous H2S synthesis with DL-propargylglycine impaired ATP-induced Ca2+ inflow, whereas it did not affect Ca2+ mobilization. These data provide the first evidence that H2S may stimulate Ca2+ influx into ECs by recruiting the reverse-mode of NCX and KATP channels. In addition, they show that such gasotransmitter may modulate the Ca2+ signals elicited by physiological stimuli in intact endothelium.

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2008

Antioxidants

Canadian Journal of Physiology and Pharmacology

Oxidative Medicine and Cellular Longevity

Redox Biology

Oxidative Medicine and Cellular Longevity, 2016

Sport Sciences for Health, 2015

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2008

Progress in Inorganic Chemistry, 2005

Life Sciences, 2005

Current Pharmaceutical Biotechnology, 2011

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2008