Nitrotyrosine as an Oxidative Stress Marker: Evidence for Involvement in Neurologic Outcome in Human Traumatic Brain Injury

Darwish, Ribal; Amiridze, Nana; Aarabi, Bizhan

doi:10.1097/ta.0b013e318069178a

Cited by 95 publications

(70 citation statements)

References 13 publications

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“…Interestingly, hemin therapy abated oxidative stress by suppressing 8-isoprostane and nitrotyrosine, two important markers of oxidative stress (12,13,30). The attenuation of oxidative stress was accompanied by the enhancement of antioxidants, including SOD, bilirubin, and ferritin, with subsequent potentiation of the total antioxidant status in GK rats.…”

Section: Discussionmentioning

confidence: 97%

“…The soleus muscle was homogenized with a cocktail of protease inhibitors and centrifuged as we previously described (27,47,49). Briefly, proteins were extracted and quantified by Bradford assay, and aliquots of 50 g were loaded on a 10% SDS-polyacrylamide gel for GSK-3, AMPK, and nitrotyrosine, a marker of oxidative stress (12,30), and 12.5% for GLUT4. The fractionated proteins were electrophoretically transferred to nitrocellulose paper and nonspecific bindings blocked with 3% nonfat milk dissolved in PBS and were incubated overnight with primary antibodies against nitrotyrosine (Santa Cruz Biotechnology), GSK-3 (Stressgen Biotech), AMPK (Cell Signaling Technology, Danvers, MA), and GLUT4 (Abcam, Cambridge, MA).…”

Section: Determination Of Insulin Resistance By Homeostasis Model Assmentioning

confidence: 99%

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Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes

Ndisang

Lane²,

Jadhav³

2009

American Journal of Physiology-Endocrinology and Metabolism

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Ndisang JF, Lane N, Jadhav A. Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes. Am J Physiol Endocrinol Metab 296: E1029-E1041, 2009. First published February 10, 2008 doi:10.1152/ajpendo.90241.2008.-In type 2 diabetes (T2D), postprandial and fasting hyperglycemia are important predictors of cardiovascular diseases; however, few drugs are currently available to simultaneously suppress these conditions. Here, we report an enduring antidiabetic effect of the heme oxygenase (HO) inducer hemin on Goto-Kakizaki rats (GK), a nonobese insulinresistant T2D model. HO breaks down the heme-moiety-generating antioxidants (biliverdin/bilirubin and ferritin) and carbon monoxide, which stimulate insulin secretion. Hemin induces HO-1 to potentiate HO activity and the HO-derived products. Chronically applied hemin (30 mg/kg ip) for a month reduced and maintained fasting glucose at physiological levels for 3 mo. Before therapy, glucose levels were 9.3 Ϯ 0.3 mmol/l (n ϭ 14). At 1, 2, and 3 mo posttherapy, we recorded 6.7 Ϯ 0.13, 5.9 Ϯ 0.2, and 7.2 Ϯ 0.2 mmol/l, respectively. Hemin was also effective against postprandial hyperglycemia (14.6 Ϯ 1.1 vs. 7.5 Ϯ 0.4 mmol/l; n ϭ 14; P Ͻ 0.01), and the effect remained sustained for 3 mo after therapy. The reduction of hyperglycemia was accompanied by enhanced HO-1, HO activity, and cGMP of the soleus muscle, alongside increased plasma bilirubin, ferritin, SOD, total antioxidant capacity, and insulin levels, whereas markers/mediators of oxidative stress like urinary-8-isoprostane and soleus muscle nitrotyrosine, NF-B, and activator protein-1 and -2 were abated. Furthermore, inhibitors of insulin signaling including soleus muscle glycogen synthase kinase-3 and JNK were reduced, while the insulinsensitizing adipokine, adiponectin, alongside AMPK were increased. Correspondingly, hemin improved glucose tolerance, suppressed insulin intolerance, reduced insulin resistance, and overturned the inability of insulin to enhance glucose transporter 4, a protein required for glucose uptake. Hemin also upregulated HO-1/HO activity and cGMP and lowered glucose in euglycemic Sprague-Dawley control rats albeit less intensely, suggesting greater selectivity of the HO system in diabetic conditions. In conclusion, reduced oxidative stress alongside the concomitant and paradoxical enhancement of insulin secretion and insulin-sensitizing pathways may account for the 3-moenduring antidiabetic effect. The synergistic interaction among HO, adiponectin, and GLUT4 may be explored against insulin-resistant diabetes.adiponectin; insulin resistance; oxidative stress; glucose transporter 4; glycogen synthase kinase-3; nuclear factor-B; activating protein-

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Section: Discussionmentioning

confidence: 97%

Section: Determination Of Insulin Resistance By Homeostasis Model Assmentioning

confidence: 99%

Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes

Ndisang

Lane²,

Jadhav³

2009

American Journal of Physiology-Endocrinology and Metabolism

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“…Instead we measured nitrotyrosine, a downstream, validated surrogate of nitric oxide formation. 18,19 Nitrotyrosine (Northwest Life Science Specialties, LLC) was detected by enzyme-linked immunoadsorbent assay (ELISA). Cytokines were also measured by ELISA (R&D Systems).…”

Section: Study Protocolmentioning

confidence: 99%

Intraosseous Versus Intravenous Infusion of Hydroxocobalamin for the Treatment Of Acute Severe Cyanide Toxicity in a Swine Model

Bebarta

Pitotti

Boudreau

et al. 2014

Academic Emergency Medicine

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Objectives: Easily administrated cyanide antidotes are needed for first responders, military troops, and emergency department staff after cyanide exposure in mass casualty incidents or due to smoke inhalation during fires involving many victims. Hydroxocobalamin has proven to be an effective antidote, but cannot be given intramuscularly because the volume of diluent needed is too large. Thus, intraosseous (IO) infusion may be an alternative, as it is simple and has been recommended for the administration of other resuscitation drugs. The primary objective of this study was to compare the efficacy of IO delivery of hydroxocobalamin to intravenous (IV) injection for the management of acute cyanide toxicity in a well-described porcine model. Methods:Twenty-four swine (45 to 55 kg) were anesthetized, intubated, and instrumented with continuous mean arterial pressure (MAP) and cardiac output monitoring. Cyanide was continuously infused until severe hypotension (50% of baseline MAP), followed by IO or IV hydroxocobalamin treatment. Animals were randomly assigned to receive IV (150 mg/kg) or IO (150 mg/kg) hydroxocobalamin and monitored for 60 minutes after start of antidotal infusion. The primary outcome measure was the change in MAP after antidotal treatment from onset of hypotension (time zero) to 60 minutes. A sample size of 12 animals per group was determined by group size analysis based on power of 80% to detect a one standard deviation of the mean MAP between the groups with an alpha of 0.05. Whole blood cyanide, lactate, pH, nitrotyrosine (nitric oxide marker) levels, cerebral and renal near infrared spectrometry (NIRS) oxygenation, and inflammatory markers were also measured. Repeated-measures analysis of variance was used to determine statistically significant changes between groups over time.Results: At baseline and at the point of hypotension, physiologic parameters were similar between groups. At the conclusion of the study, 10 out of 12 animals in the IV group and 10 out of 12 in IO group survived (p = 1.0). Both groups demonstrated a similar return to baseline MAP (p = 0.997). Cardiac output, oxygen saturation, and systemic vascular resistance were also found to be similar between groups (p > 0.4), and no difference was detected between bicarbonate, pH, and lactate levels (p > 0.8). Cyanide levels were undetectable after the hydroxocobalamin infusion throughout the study in both groups (p = 1.0). Cerebral and renal NIRS oxygenation decreased in parallel to MAP during cyanide infusion and increased after antidote infusion in both groups. Serum nitrotyrosine increased during cyanide infusion in all animals and then decreased in both study arms after hydroxocobalamin infusion (p > 0.5). Serum cytokines increased starting at cyanide infusion and no difference was detected between groups (tumor necrosis factor-a, interleukin [IL]-1b, IL-6, and IL-10).

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“…Levels of ascorbate and glutathione were both decreased in the CSF of infants following TBI (Bayir et al, 2002). The levels of 3-nitrotyrosine, a marker of nitrosylative stress, increased in the CSF of adult patients with TBI (Darwish et al, 2007). After severe TBI, the levels of beta-amyloid fragments (Aß1-42) were enhanced in the CSF (Emmerling et al, 2000).…”

Section: Oxidative Stress In Penetrating Tbimentioning

confidence: 99%

Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI

Prasad¹,

Bondy

2015

Brain Research

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AnxietyPsychological damage a b s t r a c t Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain.

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Nitrotyrosine as an Oxidative Stress Marker: Evidence for Involvement in Neurologic Outcome in Human Traumatic Brain Injury

Cited by 95 publications

References 13 publications

Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes

Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes

Intraosseous Versus Intravenous Infusion of Hydroxocobalamin for the Treatment Of Acute Severe Cyanide Toxicity in a Swine Model

Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI

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