19 documents found, page 1 of 2

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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...


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) ...


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....


Noncleavable poly(ADP-ribose) polymerase-1 regulates the inflammatbn response i...

Petrilli, V; Herceg, Z; Hassa, PO; Patel, NSA; Di Paola, R; Cortes, U; Dugo, L; Filipe, HM; Thiemermann, C; Hottiger, MO; Cuzzocrea, S; Wang, ZQ

Poly(ADP-ribosyl)ation is rapidly formed in cells following DNA damage and is regulated by poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 is known to be involved in various cellular processes, such as DNA repair, genomic stability, transcription, and cell death. During apoptosis, PARP-1 is cleaved by caspases to generate 89-kDa and 24-kDa fragments, a hallmark of apoptosis. This cleavage is thought to be a regu...


The tyrosine kinase inhibitor tyrphostin AG126 reduces renal ischemia/reperfusi...

Chatterjee, PK; Patel, NSA; Kvale, EO; Brown, PAJ; Stewart, KN; Britti, D; Cuzzocrea, S; Mota-Filipe, H; Thiemermann, C

Background. We investigate the effects of tyrphostin AG126, an inhibitor of tyrosine kinase activity, on the renal dysfunction and injury caused by ischemia/reperfusion (I/R) of the kidney. Methods. Tyrphostin AG126 (5 mg/kg intraperitoneally) was administered to male Wistar rats 30 minutes prior to bilateral renal ischemia for 45 minutes followed by reperfusion for up to 48 hours. Biochemical markers of renal ...


Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ische...

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

Background/Aims: Recent evidence indicates that peroxisome-proliferator activated receptor (PPAR) agonists protect against ischemia/reperfusion (I/R) injury. Here we investigate the effects of the PPAR-gamma agonists, rosiglitazone and ciglitazone, on the renal dysfunction and injury caused by I/R of the rat kidney in vivo. Methods: Rosiglitazone or ciglitazone were administered to male Wistar rats prior to and...


Reconstituted high-density lipoprotein attenuates organ injury and adhesion mol...

McDonald, MC; Dhadly, P; Cockerill, GW; Cuzzocrea, S; Mota-Filipe, H; Hinds, CJ; Miller, NE; Thiemermann, C

The salutary effects of high-density lipoproteins (HDLs) in animal and human models of endotoxic shock have in the past been attributed to the ability of this lipoprotein to bind to lipopolysaccharide. However, the precise mechanisms for the protective effect of HDL are unclear. The first objective of this study was to determine the effects of HDLs on the organ injury and dysfunction associated with acute sever...


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