4-hydroxy-2-nonenal and Edema

Carnosine's (CARN) anti-inflammatory potential in autoimmune diseases has been but scarcely investigated as yet. The aim of this study was to evaluate the therapeutic potential of CARN in rat adjuvant arthritis, in the model of carrageenan induced hind paw edema (CARA), and also in primary culture of chondrocytes under H2O2 injury. The experiments were done on healthy animals, arthritic animals, and arthritic animals with oral administration of CARN in a daily dose of 150 mg/kg b.w. during 28 days as well as animals with CARA treated by a single administration of CARN in the same dose. CARN beneficially affected hind paw volume and changes in body weight on day 14 and reduced hind paw swelling in CARA. Markers of oxidative stress in plasma and brain (malondialdehyde, 4-hydroxynonenal, protein carbonyls, and lag time of lipid peroxidation) and also activity of gamma-glutamyltransferase were significantly corrected by CARN. CARN also reduced IL-1alpha in plasma. Suppression of intracellular oxidant levels was also observed in chondrocytes pretreated with CARN. Our results obtained on two animal models showed that CARN has systemic anti-inflammatory activity and protected rat brain and chondrocytes from oxidative stress. This finding suggests that CARN might be beneficial for treatment of arthritic diseases.

Topics: Adjuvants, Immunologic; Aldehydes; Animals; Arthritis, Experimental; Body Weight; Carnosine; Carrageenan; Cell Survival; Cells, Cultured; Chondrocytes; Edema; Hydrogen Peroxide; Interleukin-1alpha; Intracellular Space; Luminescent Measurements; Male; Malondialdehyde; Oxidative Stress; Protein Carbonylation; Rats, Inbred Lew; Rats, Wistar

Despite successful revascularization, reperfusion after prolonged ischemia causes ischemia reperfusion (I/R) injury. Recruitment and activation of neutrophils is thought to be a key event causing I/R injury. We examined whether post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier without neutrophils, could reduce I/R injury in a rat transient middle cerebral artery occlusion (MCAO) model. Male Sprague-Dawley rats were subjected to 2-h MCAO and then were divided into three groups: (1) LEH group (n=7) infused with LEH (Hb concentration of 6g/dl, 10ml/kg/h) through the recanalized internal carotid artery for 2h, (2) vehicle group (n=8) infused with saline (10ml/kg/h) in the same manner as the LEH group, and (3) control group (n=9) subjected to recanalization only. After 24-h reperfusion, all rats were tested for neurological score and then sacrificed to examine infarct and edema volumes, myeloperoxidase (MPO) expression, matrix metalloproteinase-9 (MMP-9) expression and activity, and reactive oxygen species (ROS) production. Compared with the control group and the vehicle group, the LEH group showed a significantly better neurological score and significantly smaller infarct and edema volumes. MPO expression, MMP-9 expression and activity, and ROS production in the LEH group were also significantly lower than those in the control and vehicle groups. The results in the present study suggest that post-ischemic intra-arterial infusion of LEH can reduce I/R injury through reducing the effect of MMP-9, most likely produced by neutrophils. This therapeutic strategy may be a promising candidate to prevent I/R injury after thrombolysis and/or thromboectomy.

Topics: Aldehydes; Animals; Brain; Brain Ischemia; Carotid Artery, Internal; Edema; Hemoglobins; Humans; Infarction, Middle Cerebral Artery; Infusions, Intra-Arterial; Liposomes; Male; Matrix Metalloproteinase 9; Peroxidase; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Severity of Illness Index

To cast light on the mechanisms underlying development of spontaneous pancreatitis lesions, tissues from WBN/Kob rats at various ages were histopathologically and immunohistochemically investigated with special reference to the existence of the lipid peroxidation products 4-hydroxy-2-nonenal (HNE), 4-hydroxy-2-hexenal (HHE), and malondialdehyde (MDA). Male 4-20-week-old WBN/Kob rats were killed to allow sampling of pancreatic tissues, which were fixed in cold acetone and 10% neutral-buffered formalin. and then processed for routine histopathology as well as immunohistochemistry for proteins modified by HNE, HHE, and MDA. Although no remarkable histologic changes were noted in younger animals, edema, hemorrhage, inflammatory cell infiltration, fibrosis, vacuolation of acinar cells, and ductular proliferation were observed in exocrine pancreatic tissue from animals at 10-15 weeks of age. In animals aged 20 weeks, the lesions had progressed remarkably and deposits of hemosiderin were apparent with fibrosis. Immunohistochemical examination for lipid peroxidation product-modified proteins showed HNE and MDA to be negative in all pancreatic tissues, but HHE was positive in the areas involving atrophy of acinar cells and fibrosis in the islets. The results of the present study thus provide support for the conclusion that lipid peroxidation during spontaneous pancreatitis in WBN/Kob rats may possibly be involved in the development of diabetes in this model.

Topics: Aging; Aldehydes; Amylases; Animals; Edema; Fibrosis; Hemorrhage; Immunohistochemistry; Lipase; Lipid Peroxidation; Male; Malondialdehyde; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Inbred Strains; Vacuoles