Protective effects of anthocyanins from blackberry in a rat model of acute lung inflammation.

Anthocyanins are a group of naturally occuring phenolic compounds related to the coloring of plants, flowers and fruits. These pigments are important as quality indicators, as chemotaxonomic markers and for their antioxidant activities. Here, we have investigated the therapeutic efficacy of anthocyanins contained in blackberry extract (cyanidin-3-O-glucoside represents about 80% of the total anthocyanin contents) in an experimental model of lung inflammation induced by carrageenan in rats.

2-Cyclopenten-1-one and prostaglandin J2 reduce restenosis after balloon angioplasty in rats: role of NF-kappaB.

The aim of this study was to evaluate, using a rat model of balloon angioplasty, whether prostaglandin (PG) J(2) and 2-cyclopenten-1-one are able to reduce restenosis. We found that both PGJ(2) and 2-cyclopenten-1-one, administered by local application on carotid arteries, caused a dose-dependent inhibition of neointimal formation. Furthermore, both agents prevented vascular negative remodeling.

The tyrosine kinase inhibitor tyrphostin AG126 reduces renal ischemia/reperfusion injury in the rat.

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 dysfunction and injury were measured and renal sections assessed for renal injury.

On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies.

The list of pathophysiological conditions associated with the overproduction of superoxide expands every day. Much of the knowledge compiled on the role of this radical in disease has been gathered using the native superoxide dismutase enzyme and, more recently, by the use of superoxide dismutase knockout models or transgenic models that overexpress the various isoforms of the enzyme. Although the native enzyme has shown promising anti-inflammatory properties in both preclinical and clinical studies, there were drawbacks and issues associated with its use as a therapeutic agent and pharmacological tool.

Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis models.

Recent studies indicated that the nicotinamide dinucleotide phosphate oxidase (NADPH) oxidase-derived oxygen radicals plays a deleterious role in arthritis. To study this in more detail, gonarthritis was induced in NADPH oxidase-deficient mice. Mice received an intraarticular injection of either zymosan, to elicit an irritant-induced inflammation, or poly-L-lysine coupled lysozyme, to evoke an immune-complex mediated inflammation in passively immunized mice.

Rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2, ligands of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), reduce ischaemia/reperfusion injury of the gut.

1. The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid and thyroid hormone receptors. The thiazolidinedione rosiglitazone and the endogenous cyclopentenone prostaglandin (PG)D2 metabolite, 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2), are two PPAR-gamma ligands, which modulate the transcription of target genes.

Tyrphostin reduces the organ injury in haemorrhagic shock: role of inducible nitric oxide synthase.

We investigate the effects of the tyrosine kinase inhibitor, tyrphostin AG126 on the organ injury and dysfunction (kidney, liver, pancreas, muscle and or brain) associated with haemorrhagic shock in the anaesthetised rat. Haemorrhage (sufficient to lower mean arterial blood pressure to 45 mmHg for 90 min) and subsequent resuscitation with the shed blood resulted (within 4 h after resuscitation) in expression of inducible nitric oxide synthase inhibitor (iNOS), positive staining for nitrotyrosine (liver), renal, liver and pancreatic injury, and injury to the muscle and brain. Pre-treatment (30 min prior to the onset of haemorrhage) with the tyrosine kinase inhibitor tyrphostin AG126 reduced the iNOS expression, nitrotyrosine formation, hepatic, brain or muscular injury, and to a lesser extent, the renal injury caused by haemorrhage and resuscitation.

5-lipoxygenase knockout mice exhibit a resistance to acute pancreatitis induced by cerulein.

Here we compare the degree of pancreatitis caused by cerulein in mice lacking 5-lipoxygenase (5-LO) and in the corresponding wild-type mice. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde).

5-lipoxygenase knockout mice exhibit a resistance to splanchnic artery occlusion shock.

In the present study, we used 5-lipoxygenase (5-LO) knockout (KO) mice to evaluate the possible role of 5-LO on the pathogenesis of splanchnic artery occlusion (SAO) shock. SAO shock was induced in mice by clamping both the superior mesenteric artery and the celiac artery for 30 min, followed thereafter by release of the clamp (reperfusion). At 120 min after reperfusion, animals were sacrificed for histological examination and biochemical studies.

Pyrrolidine dithiocarbamate attenuates the development of organ failure induced by zymosan in mice.

Objective: Nuclear factor (NF) kappaB is a transcription factor which plays a pivotal role in the induction of genes involved in physiological processes as well as in the response to injury and inflammation. Dithiocarbamates are anti-oxidants which are potent inhibitors of NF-kappaB. We postulated that pyrrolidine dithiocarbamate (PDTC) would attenuate multiple-organ failure (MOF).

Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ischemia/reperfusion injury.

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 during reperfusion.

High density lipoprotein (HDL) reduces renal ischemia/reperfusion injury.

High-density lipoproteins (HDL) have been shown to reduce organ injury and mortality in animal models of shock via modulation of the expression of adhesion molecules and pro-inflammatory enzymes. As renal inflammation plays an important role in the development of ischemia/reperfusion (I/R) injury of the kidney, the aim of this study was to investigate the ability of HDL to alleviate renal dysfunction and injury in a rat model of renal I/R. HDL (80 mg/kg, intravenous) was administered to male Wistar rats 30 min before bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h.

Protective effects of cyanidin-3-O-glucoside from blackberry extract against peroxynitrite-induced endothelial dysfunction and vascular failure.

Anthocyanins are a group of naturally occurring phenolic compounds as colorants in several plants, flowers and fruits. These pigments have a great importance as quality indicators, as chemotaxonomic markers and antioxidants. The content of blackberry (Rubus species) juice was investigated by HPLC/ESI/MS using narrow bore HPLC columns.

A nonpeptidyl mimic of superoxide dismutase, M40403, inhibits dose-limiting hypotension associated with interleukin-2 and increases its antitumor effects.

Interleukin-2 (IL-2) is used to treat metastatic renal cell carcinoma and malignant melanoma, but its use is limited by the severe hypotension it produces. We have shown here that M40403, a superoxide dismutase (SOD) mimetic, blocked IL-2-induced hypotension and allowed the dose of IL-2 to be increased in mice. The reversal of IL-2-mediated hypotension was associated with an increase in plasma catecholamines.

Copper induces type II nitric oxide synthase in vivo.

Intravenous administration of copper (up to a final concentration of ca. 35 micromol/l in the plasma) led to a progressive, dramatic fall of mean arterial pressure in rats. Copper-induced pressure changes were comparable to those elicited by 2 mg/kg LPS, and were greatly prevented by previous infusion of the inducible NOS (NOS-II) inhibitors aminoguanidine or l-N(6)-(L-imino-ethyl)lysine.

A superoxide dismutase mimetic with catalase activity (EUK-8) reduces the organ injury in endotoxic shock.

Reactive oxygen species contribute to the multiple organ failure in endotoxic shock. Here, we investigate the effects of a salen-manganese complex, which exhibits both superoxide dismutase and catalase activity (EUK-8), on the circulatory failure, renal and liver injury and dysfunction caused by endotoxin in the anaesthetised rat. Endotoxaemia (6 mg/kg i.

GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury.

Background: Generation of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) may contribute to renal ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of GW274150, a novel, highly selective, potent and long-acting inhibitor of iNOS activity in rat and mouse models of renal I/R.

Methods: Rats were administered GW274150 (5 mg/kg intravenous bolus administered 30 minutes prior to I/R) and subjected to bilateral renal ischemia (45 minutes) followed by reperfusion (6 hours).

Effects of cloricromene, a coumarin derivative, on endotoxin-induced uveitis in Lewis rats.

Purpose: To investigate the effects of cloricromene, a coumarin derivative, in rats subjected to endotoxin-induced uveitis (EIU).

Methods: Endotoxin uveitis was induced in male Lewis rats by a single footpad injection of 200 microg lipopolysaccharide (LPS). Cloricromene was topically applied to the rat eye twice at 1 hour before and 7 hours after injection of LPS.

The cyclopentenone prostaglandin 15-deoxy-delta(12,14)- PGJ2 attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat.

1. Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte infiltration, and increased expression of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) in the colon. Recent evidence also suggests that the cyclopentenone prostaglandin (PG) 15-deoxy-delta(12,14)-PGJ(2) (15d- PGJ(2)) functions as an early anti-inflammatory signal.

Inducible nitric oxide synthase mediates bone loss in ovariectomized mice.

Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms we have recently demonstrated that estrogen exhibits antiinflammatory activity by preventing the induction of inducible nitric oxide synthase (iNOS) and other components of the inflammatory reaction. To verify whether this could explain the estrogen-dependent blockade of osteoporosis, we investigated the effect of ovariectomy in mice in which iNOS activity had been blunted by genetic or pharmacological manipulation.

Therapeutic potential of superoxide dismutase mimetics as therapeutic agents in critical care medicine.

Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants, or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidative stress and exaggerated production of reactive oxygen species play a major role in several aspects of septic shock and ischemia and reperfusion. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na /K adenosine triphosphatase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of reactive oxygen species.

Regulation of prostaglandin generation in carrageenan-induced pleurisy by inducible nitric oxide synthase in knockout mice.

In the present study, by comparing the responses in wild-type mice (iNOSWT) and mice lacking (iNOSKO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the correlation between endogenous nitric oxide (NO) and prostaglandin (PG) generation in carrageenan-induced pleurisy. The inflammatory response in iNOSKO mice was significantly reduced in respect to iNOSWT animals, as demonstrated by the exudate volume (-63%) and numbers of infiltrating cells (-62%). The levels of NOx in the pleural exudate from carrageenan-treated mice were significantly (p < 0.