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The non-anticoagulant heparin-like K5 polysaccharide derivative K5-N,OSepi attenuates myocardial ischaemia/reperfusion injury.

Collino M, Massimo C, Pini A, Alessandro P, Mastroianni R, Rosanna M, Benetti E, Elisa B, Lanzi C, Cecilia L, Bani D, Daniele B, Jacopo C, Manoni M, Marco M, Fantozzi R, Roberto F, Masini E, Emanuela M - J. Cell. Mol. Med. (2012)

Bottom Line: Chemical and enzymatic modifications of K5 polysaccharide have shown the possibility of producing heparin-like compounds with low anticoagulant activity and strong anti-inflammatory effects.Furthermore, K5-N,OSepi administration attenuated the increase in caspase 3 activity, Bid and Bax activation and ameliorated the decrease in expression of Bcl-2 within the ischaemic myocardium.In conclusion, we demonstrate that the cardioprotective effect of the non-anticoagulant K5 derivative K5-N,OSepi is secondary to a combination of anti-apoptotic and anti-inflammatory effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy.

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Effects of K5-N,OSepi on myocardial infarct size evoked by regional I/R. (A) Dose–response effects of K5-N,OSepi (0.1–1 mg/kg) on the extension of left ventricular myocardium with I/R-induced injury, as evaluated on hearts stained with nitro-blue tetrazolium and (B) quantification of infarct size after I/R injury, expressed as per cent of area at risk (AAR), in the absence (vehicle) or presence of K5-N,OSepi (0.3–1 mg/kg) or B4/100 (1 mg/kg). Data are means ± SEM of six animals/group. *P < 0.01 versus vehicle (1 hr reperfusion) and •P < 0.01 versus vehicle (24 hrs reperfusion).
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fig01: Effects of K5-N,OSepi on myocardial infarct size evoked by regional I/R. (A) Dose–response effects of K5-N,OSepi (0.1–1 mg/kg) on the extension of left ventricular myocardium with I/R-induced injury, as evaluated on hearts stained with nitro-blue tetrazolium and (B) quantification of infarct size after I/R injury, expressed as per cent of area at risk (AAR), in the absence (vehicle) or presence of K5-N,OSepi (0.3–1 mg/kg) or B4/100 (1 mg/kg). Data are means ± SEM of six animals/group. *P < 0.01 versus vehicle (1 hr reperfusion) and •P < 0.01 versus vehicle (24 hrs reperfusion).

Mentions: The results of the computer-assisted morphometry on the I/R hearts stained with nitroblue tetrazolium showed that administration of K5-N,OSepi 15 min. before reperfusion induced a significant reduction in the extension of myocardial damage in comparison with the non-treated rats at both 1 hr and 24 hrs (Fig. 1A). The mean size of ischaemic lesions in the rats treated with K5-N,OSepi was reduced in a dose-dependent manner at 1 hr reperfusion, with a maximum effect at 1 mg/kg (50% reduction). The highest dose of K5-N,OSepi evoked a similar 50% reduction in infarct volume when measured after 24 hrs reperfusion.


The non-anticoagulant heparin-like K5 polysaccharide derivative K5-N,OSepi attenuates myocardial ischaemia/reperfusion injury.

Collino M, Massimo C, Pini A, Alessandro P, Mastroianni R, Rosanna M, Benetti E, Elisa B, Lanzi C, Cecilia L, Bani D, Daniele B, Jacopo C, Manoni M, Marco M, Fantozzi R, Roberto F, Masini E, Emanuela M - J. Cell. Mol. Med. (2012)

Effects of K5-N,OSepi on myocardial infarct size evoked by regional I/R. (A) Dose–response effects of K5-N,OSepi (0.1–1 mg/kg) on the extension of left ventricular myocardium with I/R-induced injury, as evaluated on hearts stained with nitro-blue tetrazolium and (B) quantification of infarct size after I/R injury, expressed as per cent of area at risk (AAR), in the absence (vehicle) or presence of K5-N,OSepi (0.3–1 mg/kg) or B4/100 (1 mg/kg). Data are means ± SEM of six animals/group. *P < 0.01 versus vehicle (1 hr reperfusion) and •P < 0.01 versus vehicle (24 hrs reperfusion).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3822989&req=5

fig01: Effects of K5-N,OSepi on myocardial infarct size evoked by regional I/R. (A) Dose–response effects of K5-N,OSepi (0.1–1 mg/kg) on the extension of left ventricular myocardium with I/R-induced injury, as evaluated on hearts stained with nitro-blue tetrazolium and (B) quantification of infarct size after I/R injury, expressed as per cent of area at risk (AAR), in the absence (vehicle) or presence of K5-N,OSepi (0.3–1 mg/kg) or B4/100 (1 mg/kg). Data are means ± SEM of six animals/group. *P < 0.01 versus vehicle (1 hr reperfusion) and •P < 0.01 versus vehicle (24 hrs reperfusion).
Mentions: The results of the computer-assisted morphometry on the I/R hearts stained with nitroblue tetrazolium showed that administration of K5-N,OSepi 15 min. before reperfusion induced a significant reduction in the extension of myocardial damage in comparison with the non-treated rats at both 1 hr and 24 hrs (Fig. 1A). The mean size of ischaemic lesions in the rats treated with K5-N,OSepi was reduced in a dose-dependent manner at 1 hr reperfusion, with a maximum effect at 1 mg/kg (50% reduction). The highest dose of K5-N,OSepi evoked a similar 50% reduction in infarct volume when measured after 24 hrs reperfusion.

Bottom Line: Chemical and enzymatic modifications of K5 polysaccharide have shown the possibility of producing heparin-like compounds with low anticoagulant activity and strong anti-inflammatory effects.Furthermore, K5-N,OSepi administration attenuated the increase in caspase 3 activity, Bid and Bax activation and ameliorated the decrease in expression of Bcl-2 within the ischaemic myocardium.In conclusion, we demonstrate that the cardioprotective effect of the non-anticoagulant K5 derivative K5-N,OSepi is secondary to a combination of anti-apoptotic and anti-inflammatory effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy.

Show MeSH
Related in: MedlinePlus