Redox status related activation of endoplasmic reticulum stress and apoptosis caused by 4-hydroxynonenal exposure in INS-1 cells

4-Hydroxynonenal (HNE), a diffusible aldehyde product of membrane lipid peroxidation, can be produced by oxidative stress and has been detected in several diseases such as diabetes. In this study, we investigated the effects of HNE exposure on cytotoxicity, intracellular redox status, endoplasmic reticulum (ER) stress and apoptosis in insulinoma cell line (INS-1). Short-term (1 h) incubation of INS-1 cells with 0-50 mu M HNE decreased cell viability and caused depletion in reduced glutathione (GSH) levels and increased intracellular HNE-histidine adducts in a concentration-dependent manner. HNE activated the ER stress, leading to an increase in inositol-requiring enzyme-1a IRE1-alpha, phosphorylation of protein kinase-like ER kinase, phosphorylation of c-Jun N-terminal kinase (JNK) and increased the expression of CCAAT/enhancer binding protein (CHOP). Western blot analysis showed that HNE exposure induced dose-dependent activation of caspase 9 and caspase 3. These data indicate a potential role for HNE promoting deleterious effects toward pancreatic beta cell redox status and beta cell mass which may be important for the pathogenesis in diabetes

Inhibition of ErbB2 by Herceptin reduces viability and survival, induces apoptosis and oxidative stress in Calu-3 cell line

Human epidermal growth factor receptor 2 (ErbB2) amplification and overexpression has been seen in many cancer types including non-small cell lung cancer (NSCLC). Thus, ErbB2 is an important target for cancer therapies. Increased ErbB2 expression has been associated with drug resistance in cancer cells. Herceptin is a humanized monoclonal antibody that targets the extracellular domain of ErbB2. In this study, we aimed to block ErbB2 signaling with Herceptin and assess cytotoxicity and effects on apoptosis, oxidative stress, nuclear factor kappa-B (NF-kB), and Survivin expression in Calu-3 cell line. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay were used to assess cell viability as a marker of proliferation. Acridine orange/ethidium bromide (AO/EB) staining and caspase 3/7 activity were measured as the markers of apoptosis. The relative expressions of NF-kB-p50 and Survivin mRNAs were evaluated. Activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), and the levels of glutathione (GSH) and reactive oxygen species (ROS) were determined in a time- and dose-dependent manner. Our results show that Herceptin treatment inhibits cell proliferation and activates apoptosis but without effects on Survivin and NF-kB expression in Calu-3 cell line. Intracellular glutathione levels and SOD and CAT activities were decreased in a time- and dose-dependent manner associated with oxidative stress. Also, ROS were increased at 24 h. These results provide evidence that Herceptin can be used as a cytotoxic and apoptotic agent in NSCLC

Effects of ketamine, propofol, and ketofol on proinflammatory cytokines and markers of oxidative stress in a rat model of endotoxemia-induced acute lung injury

Intravenous lipopolysaccharide (LPS) leads to acute lung injury (ALI) in rats. The purpose of this study was to examine the anti-inflammatory and antioxidant efficacy of ketamine, propofol, and ketofol in a rat model of ALI. We induced ALI in rats via intravenous injection of LPS (15 mg kg(-1)). The animals were randomly separated into five groups: control, LPS only, LPS + ketamine (10 mg.kg(-1).h(-1)), LPS + propofol (10 mg.kg(-1).h(-1)), LPS + ketofol (5 mg.kg(-1).h(-1) ketamine + 5 mg.kg(-1).h(-1) propofol). LPS resulted in an increase in the release of pro-inflammatory cytokines, mRNA expression related with inflammation, production of nitric oxide, and lipid peroxidation. Ketamine prevented the increase in markers of oxidative stress and inflammation mediators, both in plasma and lung tissue. Propofol decreased the levels of cytokines in plasma and lung tissue, whereas it had no effect on the IL-1-beta level in lung tissue. Ketamine downregulated mediators of lung tissue inflammation and reduced the level of circulating cytokines and protected lung tissue against lipid peroxidation. Ketofol decreased the level of INF-alpha and IL-1 beta in plasma, as well as expression of cyclooxygenase-2 mRNA and the nitrate/nitrite level in lung tissue. The results of this investigation support the hypothesis that ketamine may be effective in preventing ALI

Glycoxidative and nitrosative stress in kidney of experimental diabetic rats: Effects of the prydoindole antioxidant stobadine

OBJECTIVES: Recent basic research and clinical data have provided new insights into the role of glycoxidative and nitrosative stresses (both oxidative stress) in diabetic complications, such as diabetic nephropathy, suggesting a different and innovative approach to antioxidant therapy. In streptozotocin-induced diabetic rat kidney, the present study investigated the effects of the sythetic pyridoindole antioxidant stobadine (STB) on renal total antioxidant potential (AOP) and protein oxidation parameters such as protein carbonyl content (PCC), advanced oxidation protein products (AOPPs) and nitrotyrosine (NT), a marker specific for protein modification by peroxynitrite

Effect of long term, non cholesterol lowering dose of fluvastatin treatment on oxidative stress in brain and peripheral tissues of streptozotocin-diabetic rats

One of the main goals of treatment of diabetes mellitus is to prevent its complications. Oxidative stress is universal in diabetes, being ultimately involved with the development complications. As a result of hyperglycemia, reactive oxygen/nitrogen species are produced in various tissues that leads to tissue damage with lipid peroxidation and protein oxidation, along with disruption in cellular homeostasis and accumulation of damaged molecules. Hence, supplementation with antioxidant compounds may offer some protection against diabetic complications. The pleiotropic effects of statins, including antioxidant and anti-inflammatory properties, represent an area of great interest in prevention and therapy of cardiovascular and neurological disorders. Using biomarkers of oxidative stress, in this study we examined the effect of non cholesterol lowering dose, long term fluvastatin treatment on oxidative stress in streptozotocin-diabetic rats. Experiments were conducted in 24 Wistar adult male rats. Diabetic and non-diabetic rats were treated orally for 6 months with fluvastatin (2 mg/kg/day, p.o) starting one week after streptozotocin injection (55 mg/kg, i.p.), (preventive study). In brain, heart, liver, pancreas and kidney homogenates malondialdehyde, lipid hydroperoxide, protein carbonyl content, advanced oxidation protein products, 3-nitrotyrosine levels and superoxide dismutase, catalase activities were measured. Hyperglycemia and dyslipidemia in diabetic groups remained unchanged after fluvastatin treatment. The drug act as antioxidant in the tissues. Hence, antioxidant property of fluvastatin, independent of cholesterol lowering effect, may play a role in prevention of diabetic complications. Clinical relevance of this effect of fluvastatin seems worthy of further studies. (C) 2010 Elsevier B.V. All rights reserved

Investigation of the Correlation Between ADMA Levels and Carotid Artery Intima-Media Thickness in Rheumatoid Arthritis Patients

WOS: 000295573000002Objective: Plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, is related to increased cardiovascular risks, endothelial dysfunction and atherosclerosis. Carotid artery intima-media thickness (IMT) is closely related to the risk of coronary artery disease. We aimed to investigate plasma ADMA levels and its relation to carotid IMT in patients with rheumatoid arthritis (RA). Materials and Methods: Eighteen Turkish patients with RA (16 females, mean age: 49.44 +/- 8.88 years) and 18 age- and gender-matched healthy controls (16 females, mean age: 46.28 +/- 4.97 years) were included in the study. Measurement of IMT was done by B-mode ultrasound. Plasma ADMA levels and carotid IMT of both sides were measured in all patients and healthy controls, and the means of the two groups were compared. The correlation between ADMA levels and carotid IMT was assessed in patients with RA. Results: Plasma ADMA levels were significantly higher in patients compared to healthy controls. Although the carotid IMT values were relatively higher in the patient group than in the control group, the difference was not statistically significant. There was no significant correlation between ADMA levels and carotid IMT values. Conclusion: Our findings support the notion that plasma ADMA levels are elevated in patients with RA. Despite lack of correlation between ADMA levels and IMT in our study, ADMA levels can be used to evaluate endothelial dysfunction. Turk J Phys Med Rehab 2011;57:114-8

Renal Tissue Damage After Experimental Pyelonephritis: Role of Antioxidants and Selective Cyclooxygenase-2 Inhibitors

OBJECTIVES To investigate the involvement of oxidative stress in the pathogenesis of acute pyelonephritis, and to evaluate the impact of meloxicam and/or L-carnitine in addition to conventional antibiotic treatment