Airway inflammation induces anxiety-like behavior through neuroinflammatory, neurochemical, and neurometabolic changes in an allergic asthma model.

Allergic asthma is characterized by chronic airway inflammation and is constantly associated with anxiety disorder. Recent studies showed bidirectional interaction between the brain and the lung tissue. However, where and how the brain is affected in allergic asthma remains unclear. We aimed to investigate the neuroinflammatory, neurochemical, and neurometabolic alterations that lead to anxiety-like behavior in an experimental model of allergic asthma. Mice were submitted to an allergic asthma model induced by ovalbumin (OVA) and the control group received only Dulbecco's phosphate-buffered saline (DPBS). Our findings indicate that airway inflammation increases interleukin (IL) -9, IL-13, eotaxin, and IL-1ß release and changes acetylcholinesterase (AChE) and Na+,K+-ATPase activities in the brain of mice. Furthermore, we demonstrate that a higher reactive oxygen species (ROS) formation and antioxidant defense alteration that leads to protein damage and mitochondrial dysfunction. Therefore, airway inflammation promotes a pro-inflammatory environment with an increase of BDNF expression in the brain of allergic asthma mice. These pro-inflammatory environments lead to an increase in glucose uptake in the limbic regions and to anxiety-like behavior that was observed through the elevated plus maze (EPM) test and downregulation of glucocorticoid receptor (GR). In conclusion, the present study revealed for the first time that airway inflammation induces neuroinflammatory, neurochemical, and neurometabolic changes within the brain that leads to anxiety-like behavior. Knowledge about mechanisms that lead to anxiety phenotype in asthma is a beneficial tool that can be used for the complete management and treatment of the disease.

Taurine Chloramine decreases cell viability and cytokine production in blood and spleen lymphocytes from septic rats.

Taurine (Tau) is an abundant amino acid in polymorphonuclear leukocytes that react with hypochlorous acid to form taurine chloramine (TauCl) under inflammatory conditions. We investigated potential interactions between lymphocytes and TauCl in rats submitted to cecal ligation. Animals were divided into sham or CLP groups (24 or 120 h) to isolate lymphocytes from blood and spleen. Lymphocytes were cultured at a concentration of 1×106 cells/mL and activated by concanavalin A. Tau and TauCl were added at 1, 10, and 100 µM. Cells were incubated with MTT to evaluate cell viability and cytokine concentration in the supernatant was determined. TauCl decreased lymphocyte viability and altered the secretion pattern of important inflammatory mediators in non-specific-phenotype manner. The effort to a is elucidate mechanisms of immune cell (dys)function in sepsis is important to better understand the complex regulation of immune system during sepsis development, and further studies are necessary to confirm TauCl as potential target in this context.

N-acetylcysteine effects on a murine model of chronic critical limb ischemia.

During chronic limb ischemia, oxidative damage and inflammation are described. Besides oxidative damage, the decrease of tissue oxygen levels is followed by several adaptive responses. The purpose of this study was to determine whether supplementation with N-acetylcysteine (NAC) is effective in an animal model of chronic limb ischemia. Chronic limb ischemia was induced and animals were treated once a day for 30 consecutive days with NAC (30mg/kg). After this time clinical scores were recorded and soleus muscle was isolated and lactate levels, oxidative damage and inflammatory parameters were determined. In addition, several mechanisms associated with hypoxia adaptation were measured (vascular endothelial growth factor - VEGF and hypoxia inducible factor - HIF levels, ex vivo oxygen consumption, markers of autophagy/mitophagy, and mitochondrial biogenesis). The adaptation to chronic ischemia in this model included an increase in muscle VEGF and HIF levels, and NAC was able to decrease VEGF, but not HIF levels. In addition, ex vivo oxygen consumption under hypoxia was increased in muscle from ischemic animals, and NAC was able to decrease this parameter. This effect was not mediated by a direct effect of NAC on oxygen consumption. Ischemia was followed by a significant increase in muscle myeloperoxidase activity, as well as interleukin-6 and thiobarbituric acid reactive substances species levels. Supplementation with NAC was able to attenuate inflammatory and oxidative damage parameters, and improve clinical scores. In conclusion, NAC treatment decreases oxidative damage and inflammation, and modulates oxygen consumption under hypoxic conditions in a model of chronic limb ischemia.

LC/QTOF profile and preliminary stability studies of an enriched flavonoid fraction of Cecropia pachystachya Trécul leaves with potential antidepressant-like activity.

There is increasing interest in natural antioxidants that are candidates for the prevention of brain damage occurring in major depressive disorders. Cecropia pachystachya is a tropical tree species of Central and South America and a rich source of polyphenols, particularly flavonoids. The aim of this study was to characterize the flavonoid profile of an enriched flavonoid fraction of C. pachystachya (EFF-Cp) and evaluate the antidepressant-like effects of its acute administration in behavior, cytokine levels, oxidative stress and energy metabolism parameters. The EFF-Cp chemical characterization was performed by HPLC/DAD and LC/QTOF. The antidepressant-like effects were performed by the forced swimming test, splash test and open field test. EFF-Cp revealed 15 flavonoids, including seven new glycosyl flavonoids for C. pachystachya. Quantitatively, EFF-Cp showed isoorientin (43.46 mg/g), orientin (23.42 mg/g) and isovitexin (17.45 mg/g) as major C-glycosyl flavonoids. In addition, EFF-Cp at doses 50 and 100 mg/kg reduced the immobility time in the forced swimming test, without changing the locomotor activity and grooming time. In addition, EFF-Cp was able to prevent the oxidative damage in some brain areas. In conclusion, the results of this study suggest that EFF-Cp exerts antidepressant-like effects with its antioxidant properties.

N-acetylcysteine plus deferoxamine for patients with prolonged hypotension does not decrease acute kidney injury incidence: a double blind, randomized, placebo-controlled trial.

BACKGROUND: The aim was to test the primary hypothesis that in patients suffering from shock, treatment with N-acetylcysteine (NAC) plus deferoxamine (DFX) decreases the incidence of acute kidney injury (AKI). METHODS: A double-blind, randomized, placebo-controlled trial was conducted in a general intensive care unit in an academic hospital. Patients were included if they had new-onset hypotension, defined as mean arterial blood pressure <60 mmHg or requirement for vasopressor medication. A loading dose of NAC or placebo of 50 mg/kg in 4 h was administered intravenously. After the loading dose, patients received 100 mg/kg/day for the next 48 h. DFX or placebo was administered once at 1000 mg at a rate of 15/mg/kg/h. The primary outcome was the incidence of AKI. RESULTS: A total of 80 patients were enrolled in the study. The incidence of AKI was 67 % in the placebo arm and 65 % in the treatment group (relative risk (RR) 0.89 (0.35-2.2)). Furthermore, NAC plus DFX was effective in decreasing the severity and duration of AKI, and patients in the treatment group had lower serum creatinine levels at discharge. No severe adverse event associated with treatment was reported. The effects of NAC plus DFX could be secondary to the attenuation of early inflammatory response and oxidative damage. CONCLUSION: The administration of NAC plus DFX to critically ill patients who had a new episode of hypotension did not decrease the incidence of AKI. TRIAL REGISTRATION: Clinicaltrials.gov NCT00870883 (Registered 25 March 2009.).

Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

CD40-CD40 Ligand Pathway is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis.

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40-CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40-CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40-CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40-CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis.

The role of microglia activation in the development of sepsis-induced long-term cognitive impairment.

Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP). The animals were divided into sham-operated (Sham+control), sham-operated plus minocycline (sham+MIN), CLP (CLP+control) and CLP plus minocycline (CLP+MIN) (100 µg/kg, administered as a single intracerebroventricular (ICV) injection). Some animals were killed 24h after surgery to assess the breakdown of the blood brain barrier, cytokine levels, oxidative damage to lipids (TBARS) and proteins in the hippocampus. Some animals were allowed to recover for 10 days when step-down inhibitory avoidance and open-field tasks were performed. Treatment with minocycline prevented an increase in markers of oxidative damage and inflammation in the hippocampus after sepsis. This was associated with an improvement in long-term cognitive performance. In conclusion, we demonstrated that the inhibition of the microglia by an ICV injection of minocycline was able to decrease acute brain oxidative damage and inflammation as well as long-term cognitive impairment in sepsis survivors.

Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma.

Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD) in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA). In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p.) and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma.

Plasma nitric oxide, endothelin-1, arginase and superoxide dismutase in the plasma and placentae from preeclamptic patients.

The aim of this study was to determine parameters of NO metabolism in plasma and placenta of preeclamptic (PE) patients. It was conducted a case-control study at São José Hospital, Brazil. Thirty-three PE and 33 normotensive pregnant were included in the study. The diagnosis of PE was established in accordance with the definitions of American College of Obstetricians and Gynecologists. Peripheral venous blood and placenta samples were obtained at postpartum period. Plasma NO levels and SOD activity were significantly lower and endothelin-1 levels and arginase activity were significantly higher in PE women when compared to controls. None of the analyzed parameters were different in the placenta between groups. Our findings suggest that parameters associated with NO metabolism are altered only at the systemic level, but not in placenta of PE patients.

Oxidative stress and aging: correlation with clinical parameters.

BACKGROUND AND AIMS: The free radical theory of aging has been receiving a lot of attention in the past years. The aim of this study was to examine the correlation between oxidative damage, antioxidant enzyme activities and plasma antioxidant potential with clinical parameters in elderly people. METHODS: Elderly subjects over 80 years old were included in the study. Clinical data were collected based on the Cumulative Illness Rating Scale (n = 132). In addition, blood samples were collected to determine biochemical and oxidative stress. RESULTS: The results showed that the mean age of the participants was 85.1 ± 4.0 years old. Diabetic patients presented higher plasma protein carbonyl levels when compared with non-diabetic, and plasma levels of thiobarbituric acid-reactive substances were correlated to serum triglyceride and LDL fraction. In contrast, a lower plasma total antioxidant capacity presented a relation with the presence of diabetes and arterial hypertension. In addition, healthy elderly subjects presented a higher plasma total antioxidant capacity. CONCLUSION: Thus, it seemed that plasma antioxidant potential is a better predictor of successful aging in the elderly than oxidative damage parameters or plasma antioxidant enzyme activities.

Effect of acute administration of L-tyrosine on oxidative stress parameters in brain of young rats.

Tyrosinemia type II, also known as Richner-Hanhart syndrome, is an autosomal recessive inborn error of metabolism caused by a deficiency of hepatic cytosolic tyrosine aminotransferase, and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that studies demonstrated that high concentrations of tyrosine provoke oxidative stress in vitro and in vivo in the cerebral cortex of rats, in the present study we investigate the oxidative stress parameters (enzymatic antioxidant defenses, thiobarbituric acid-reactive substances and protein carbonyl content) in cerebellum, hippocampus and striatum of 30-old-day rats after acute administration of L-tyrosine. Our results demonstrated that the acute administration of L-tyrosine increased the thiobarbituric acid reactive species levels in hippocampus and the carbonyl levels in cerebellum, hippocampus and striatum. In addition, acute administration of L-tyrosine significantly decreased superoxide dismutase activity in cerebellum, hippocampus and striatum, while catalase was increased in striatum. In conclusion, the oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia and the administration of antioxidants may be considered as a potential adjuvant therapy for tyrosinemia, especially type II.

Gastrin-releasing peptide receptor antagonism induces protection from lethal sepsis: involvement of toll-like receptor 4 signaling.

In sepsis, toll-like receptor (TLR)-4 modulates the migration of neutrophils to infectious foci, favoring bacteremia and mortality. In experimental sepsis, organ dysfunction and cytokines released by activated macrophages can be reduced by gastrin-releasing peptide (GRP) receptor (GRPR) antagonist RC-3095. Here we report a link between GRPR and TLR-4 in experimental models and in sepsis patients. RAW 264.7 culture cells were exposed to lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α and RC-3095 (10 ng/mL). Male Wistar rats were subjected to cecal ligation and puncture (CLP), and RC-3095 was administered (3 mg/kg, subcutaneously); after 6 h, we removed the blood, bronchoalveolar lavage, peritoneal lavage and lung. Human patients with a clinical diagnosis of sepsis received a continuous infusion with RC-3095 (3 mg/kg, intravenous) over a period of 12 h, and plasma was collected before and after RC-3095 administration and, in a different set of patients with systemic inflammatory response syndrome (SIRS) or sepsis, GRP plasma levels were determined. RC-3095 inhibited TLR-4, extracellular-signal-related kinase (ERK)-1/2, Jun NH(2)-terminal kinase (JNK) and Akt and decreased activation of activator protein 1 (AP-1), nuclear factor (NF)-κB and interleukin (IL)-6 in macrophages stimulated by LPS. It also decreased IL-6 release from macrophages stimulated by TNF-α. RC-3095 treatment in CLP rats decreased lung TLR-4, reduced the migration of cells to the lung and reduced systemic cytokines and bacterial dissemination. Patients with sepsis and systemic inflammatory response syndrome have elevated plasma levels of GRP, which associates with clinical outcome in the sepsis patients. These findings highlight the role of GRPR signaling in sepsis outcome and the beneficial action of GRPR antagonists in controlling the inflammatory response in sepsis through a mechanism involving at least inhibition of TLR-4 signaling.

Protective effects of guanosine against sepsis-induced damage in rat brain and cognitive impairment.

The development of cognitive impairment in sepsis is associated with neurotoxic effects caused by oxidative stress. We have assessed the effects of acute and extended administration of guanosine (GUA) on brain oxidative stress parameters and cognitive impairment in rats submitted to sepsis by cecal ligation and perforation (CLP). To achieve this goal, male Wistar rats underwent either sham operation or CLP with GUA. Rats subjected to CLP were treated with intraperitoneal injection of GUA (8 mg/kg after CLP) or vehicle. Twelve and 24 h after CLP, the rats were sacrificed, and samples from brain (hippocampus, striatum, cerebellum, prefrontal cortex and cortex) were obtained and assayed for thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. On the 10th day, another group of rats was submitted to the behavioral tasks. GUA administration reduced TBARS and carbonyl levels in some brain regions between 12 and 24 h after CLP, and ameliorated cognitive impairment evaluated 10 days after CLP. Our data provide the first experimental demonstration that GUA was able to reduce the consequences of CLP-induced sepsis in rats, by decreasing oxidative stress parameters in the brain and recovering the memory impairment.

Erythropoietin reverts cognitive impairment and alters the oxidative parameters and energetic metabolism in sepsis animal model.

Sepsis is characterized by systemic biochemical alterations including the central nervous system in the early times and cognitive impairment at later times after sepsis induction in the animal model. Recent studies have shown that, besides its hematological activity, erythropoietin (EPO) has cytoprotective effects on various cells and tissues. In order to corroborate elucidating the effects of alternative drugs for sepsis treatment, we evaluated the effects of both acute and chronic EPO treatment on oxidative stress and energetic metabolism in the hippocampus, and cognitive impairment, respectively, after sepsis induction by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent CLP with "basic support" or sham operation. In the acute treatment, EPO was administered once immediately after CLP induction. The rats were then killed after 6 and 24 h, and the hippocampus was removed for analysis of oxidative stress and energetic metabolism, respectively. Regarding the chronic treatment, EPO was administered once daily until the 4th day after induction. Aversive memory was tested on the 10th day after surgery. It was observed that the acute use of EPO (a single dose) alters the oxidative parameters and energetic metabolism. Chronic use (4 days) reversed cognitive impairment in the sepsis animal model. Mortality rates were attenuated only during chronic treatment.

Sodium butyrate decreases the activation of NF-κB reducing inflammation and oxidative damage in the kidney of rats subjected to contrast-induced nephropathy.

BACKGROUND: Contrast-induced nephropathy (CIN) is associated with a combination of hypoxic and toxic renal tubular damage, renal endothelial dysfunction and altered intra-renal microcirculation. Recently, sodium butyrate (SB) has been focused on since it possesses anti-inflammatory activities. Thus, based on the lack of information on the effects of SB in acute kidney injury (AKI), we investigated the possible effects of SB after CIN in rats. METHODS: Wistar rats were divided into three groups: (1 sham) control, (2 MI) AKI treated with contrast medium and (3 MI + SB) AKI plus SB. Six days after contrast administration, blood and kidney were removed for the determination of creatinine, interleukin (IL)-6 levels, oxidative damage parameters and histologic analyses. Nuclear factor kappa B (NF-κB), pIκBα and vasodilator-stimulated phosphoprotein (VASP) protein content were determined by immunoblotting. RESULTS: After 6 days, the levels of creatinine increased significantly in the MI group, and this was attenuated using SB. SB treatment was associated with a decrease on the levels of lipid peroxidation, but not the protein oxidation, and IL-6 levels, as well as tubular damage. These effects are probably mediated, in part, by a decrease on the activation of NF-κB in the kidney, but not alteration in pVASP content. CONCLUSIONS: The current experiment suggests that NF-κB induced an inflammatory response after CIN and SB could inhibit NF-κB expression protecting against CIN in rats.

Association of interleukin-6 in women with persistence of DNA-HPV: a nested case-control study.

OBJECTIVE: To identify the role of Interleukin-6, IL-10 and their epidemiological association in women with persistence of DNA-HPV. DESIGN AND METHODS: A nested case-control study within a longitudinal cohort study. Cervical specimens and blood samples were collected at enrolment from asymptomatic women who looked for a service of public health in a district of Porto Alegre, Brazil. A logistic regression analysis was performed with 95% confidence intervals. The outcome was the persistence of DNA-HPV infection. RESULTS: The analysis showed that the age of the first intercourse below 20 years old (OR = 19.65, IC 95% 2.43-68.85), four or more sexual partners during lifetime (OR = 5.67, IC 95% 1.28-24.99), women with a previous altered Pap smear (OR = 10.17, IC 95% 1.80-57.33), marital status (OR = 12.94, IC 95% 2.43-68.85) and IL6 ≤ 3.106 pg/ml were associated with persistence of HPV infection. IL-10 were not associated with the HPV persistence. CONCLUSION: The present study suggests that IL-6 levels may be a marker of HPV DNA persistence, although further investigation is necessary.

Oxidative stress, cytokine/chemokine and disruption of blood-brain barrier in neonate rats after meningitis by Streptococcus agalactiae.

We verify the levels of cytokine/chemokine, myeloperoxidase activity, oxidative stress and disruption of BBB in hippocampus and cortex of the neonate Wistar rats after meningitis by S. agalactiae. In the hippocampus the levels were increased of CINC-1 at 6 h and 12 h, IL-1ß at 6, 12 and 24 h, IL-6 at 6, 24 and 96 h, IL-10 at 24, 48 and 96 h and TNF-α at 24 h and 96 h. In the cortex the CINC-1 and IL-1ß levels were found increased at 6 h. The MPO activity was significantly elevated at 24, 48 and 98 h in hippocampus and at 6, 12, 24, 48 and 96 h in the cortex. The breakdown of BBB started at 12 h.TBARS levels were elevated in the hippocampus at 6, 12, 24, 48, 72 and 96 h and cortex at 72 and 96 h. Protein carbonyls were elevated in the hippocampus and cortex at 6, 24, 48, 72 and 96 h. There was a decrease of SOD activity in hippocampus and in cortex. Catalase activity was elevated in hippocampus at 6 h and in the cortex at 12 and 96 h. Neonatal bacterial infections of the CNS are severe, the interference with the complex network of cytokines/chemokine, other inflammatory mediators and oxidants tend to aggravate the illness and can be involved in the breakdown of the BBB.

Skeletal muscle electron transport chain dysfunction after sepsis in rats.

BACKGROUND: The derangement in oxygen utilization occurring during sepsis is likely to be linked to impaired mitochondrial functioning. Skeletal muscle comprises 50%-60% of body cell mass and represents the largest organ potentially affected by systemic inflammation. Thus, we investigated whether sepsis induced by cecal ligation and puncture (CLP) modifies mitochondrial activity in respiratory and nonrespiratory skeletal muscle. MATERIALS AND METHODS: Wistar rats were subjected to CLP and at different times, diaphragm and quadriceps were removed for the determination of electron transfer chain activities and mitochondrial oxidative stress. In addition, we determined diaphragm contractile strength. RESULTS: In the quadriceps, 12 h after CLP we demonstrated a significant diminution on complex II-III activity. At late times (48 h after CLP), we demonstrated a decrease in the activity of all electron transfer chain complexes, which seemed to be secondary to early oxidative stress and correlates with diaphragm contractile strength. Differently from diaphragm, electron transfer chain was not decreased after sepsis and even oxidative stress was not increased at all times tested. CONCLUSION: Our results suggest that quadriceps mitochondria are more resistant to sepsis-induced dysfunction.

Evaluation of brain and kidney energy metabolism in an animal model of contrast-induced nephropathy.

Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients, occurring from 24 to 48 h and up to 5 days after the administration of iodinated contrast media. Encephalopathy may accompany acute renal failure and presents with a complex of symptoms progressing from mild sensorial clouding to delirium and coma. The mechanisms responsible for neurological complications in patients with acute renal failure are still poorly known, but several studies suggest that mitochondrial dysfunction plays a crucial role in the pathogenesis of uremic encephalopathy. Thus, we measured mitochondrial respiratory chain complexes and creatine kinase activities in rat brain and kidney after administration of contrast media. Wistar rats were submitted to 6.0 ml/kg meglumine/sodium diatrizoate administration via the tail vein (acute renal failure induced by contrast media) and saline in an equal volume with the radiocontrast material (control group); 6 days after, the animals were killed and kidney and brain were obtained. The results showed that contrast media administration decreased complexes I and IV activities in cerebral cortex; in prefrontal cortex, complex I activity was inhibited. On the other hand, contrast media administration increased complexes I and II-III activities in hippocampus and striatum and complex IV activity in hippocampus. Moreover, that administration of contrast media also decreased creatine kinase activity in the cerebral cortex. The present findings suggest that the inhibition of mitochondrial respiratory chain complexes and creatine kinase caused by the acute renal failure induced by contrast media administration may be involved in the neurological complications reported in patients and might play a role in the pathogenesis of the encephalopathy caused by acute renal failure.