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Effects of some natural 5-hydroxy-isoflavones on cultured human endothelial cel...

Paulo, A; Mota-Filipe, H

Due to their biological activity, it has been suggested that consumption of isoflavone-rich diets may prevent prostate and breast cancers, osteoporosis and cardiovascular diseases. Preventive effects of isoflavones on cancer and cardiovascular diseases have been associated with their oestrogenic and antioxidant properties. However, concerns still exist about the potential dangers of consuming high levels of the...


Tyrphostin AG126 reduces ischemia-reperfusion injury of the liver in the rat.

Sepodes, B; Pinto, R; McDonald, M; Eduardo-Figueira, M; Thiemermann, C; Mota-Filipe, H


Mice lacking the 110-kD isoform of poly(ADP-ribose) glycohydrolase are protecte...

Patel, NSA; Cortes, U; Di Poala, R; Mazzon, E; Mota-Filipe, H; Cuzzocrea, S; Wang, ZQ; Thiemermann, C

The role of poly(ADP-ribose) (PAR) glycohydrolase (PARG) in the pathophysiology of renal ischemia/reperfusion (I/R) injury is not known. Poly(ADP-ribosyl)ation is rapidly stimulated in cells after DNA damage caused by the generation of reactive oxygen and nitrogen species during I/R. Continuous or excessive activation of poly(ADP-ribose) polymerase-1 produces extended chains of ADP-ribose on nuclear proteins an...


Inhibitors of calpain activation (PD150606 and E-64) and renal ischemia-reperfu...

Chatterjee, PK; Todorovic, Z; Sivarajah, A; Mota-Filipe, H; Brown, PAJ; Stewart, KN; Mazzon, E; Cuzzocrea, S; Thiemermann, C

Calpain activation has been implicated in the development of ischemia-reperfusion (I-R) injury. Here we investigate the effects of two inhibitors of calpain activity, PD150606 and E-64, on the renal dysfunction and injury caused by I-R of rat kidneys in vivo. Male Wistar rats were administered PD150606 or E-64 (3 mg/kg i.p.) or vehicle (10%, v/v, DMSO) 30 min prior to I-R. Rats were subjected to bilateral renal...


Differential effects of caspase inhibitors on the renal dysfunction and injury ...

Chatterjee, PK; Todorovic, Z; Sivarajah, A; Mota-Filipe, H; Brown, PAJ; Stewart, KN; Cuzzocrea, S; Thiemermann, C

Caspase activation has been implicated in the development of ischemia-reperfusion injury. Here, we investigate the effects of different caspase inhibitors on the renal dysfunction and injury caused by ischemia-reperfusion of the rat kidney. Bilateral clamping of renal pedicles (45 min) followed by reperfusion (6 h) caused significant renal dysfunction and marked renal injury. Caspase-1 inhibitor II (N-acetyl-L-...


EUK-134 reduces renal dysfunction and injury caused by oxidative and nitrosativ...

Chatterjee, PK; Patel, NSA; Kvale, EO; Brown, PAJ; Stewart, KN; Mota-Filipe, H; Sharpe, MA; Di Paola, R; Cuzzocrea, S; Thiemermann, C

Background/Aims: Oxidative and nitrosative stress plays important roles in the pathogenesis of renal ischemia/ reperfusion (I/R) injury. Here we investigate the effect of EUK-134, a synthetic superoxide dismutase and catalase mimetic, (i) on renal dysfunction and injury caused by I/R in vivo and (ii) on proximal tubular cell (PTC) injury and death caused by oxidative and nitrosative stress. Methods: Rats, subje...


Tempol, an intracelullar free radical scavenger, reduces liver injury in hepati...

Sepodes, B; Maio, R; Pinto, R; Marques, C; Mendes-Do-Vale, J; McDonald, MC; Thiemermann, C; Mota-Filipe, H

Liver ischemia is of clinical interest because of its role in liver failure and also hepatic graft rejection. The generation of reactive oxygen species contributes to the injury that follows ischemia-reperfusion. One therapy utilizes the administration of antioxidants; however, only limited experience suggests a potential benefit of systemic administration of these compounds. To overcome the limitations of thes...


The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) ameli...

Chatterjee, PK; Patel, NSA; Cuzzocrea, S; Brown, PAJ; Stewart, KN; Mota-Filipe, H; Britti, D; Eberhardt, W; Pfeilschifter, J; Thiemermann, C

Objective: Here we investigate the effects of the endogenous prostaglandin D-2 metabolite 15-deoxy-Delta(12,14)-prostaglandin J(2), on the renal dysfunction and injury caused by ischemia/reperfusion of the kidney. Methods: Male Wistar rats, subjected to bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h, were administered 15-deoxy-Delta(12,14)-prostaglandin J(2) (1 mg/kg, intravenously) ...


Flavonoids of an extract of Pterospartum tridentatum showing endothelial protec...

Vitor, RE; Mota-Filipe, H; Teixeira, G; Borges, C; Rodrigues, AI; Teixeira, A; Paulo, A

Pterospartium tridentatum is a Leguminosae that grows spontaneously in Portugal. The flowers are used in popular medicine for the treatment of throat irritation conditions and in herbal mixtures for diabetes. Diabetic vascular complications are due, among


5-Aminoisoquinolinone reduces renal injury and dysfunction caused by experiment...

Chatterjee, PK; Chatterjee, BE; Pedersen, H; Sivarajah, A; McDonald, MC; Mota-Filipe, H; Brown, PAJ; Stewart, KN; Cuzzocrea, S; Threadgill, MD

Background. Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the development of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of a water-soluble and potent PARP inhibitor, 5-aminoisoquinolinone (5-AIQ), on the renal injury and dysfunction caused by oxidative stress of the rat kidney in vitro and in vivo....


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