Exposure to organic solvents and hepatotoxicity.

The purpose of this study was to identify the long-term effect of chemical exposure on the liver. Laboratory tests included alanine aminotransferase (ALT) dosage and oxidative stress tests, such as thiobarbituric acid reactive substances in plasma and superoxide dismutase (SOD) and glutathione S-transferase analysis in erythrocytes. The cross-sectional study comprised 70 workers, 30 of them exposed to organic solvents and 40 not exposed. All those exposed presented at least 5 years of exposure to solvents. Hepatitis B and C, known hepatic disease, comorbidities, use of alcohol, illicit drugs or hepatotoxic medications, smoking, body mass index >30, female sex and age (<18 or >65) were excluded from the sample. Results indicated that elevated ALT was more frequent in the exposed group compared to controls: 33% vs. 10.5%, with a statistical significance (p < 0.05). Thiobarbituric acid reactive substances were significantly elevated (p < 0.01) in the exposed group in comparison to controls. Antioxidant enzymes were more elevated in the exposed group compared to controls: SOD 7.29 (4.30-8.91) USOD/mg of protein vs. 3.48 (2.98-5.28) USOD/mg of protein and GST 2.57 µmol/min/mg of protein (1.80-4.78) vs. 1.81 µmol/min/mg of protein (1.45- 2.30) µM/min/mg of protein. The results suggest an association between exposure to organic solvents and hepatotoxicity.

The causal role of the occipital face area (OFA) and lateral occipital (LO) cortex in symmetry perception.

Symmetry is an important cue in face and object perception. Here we used fMRI-guided transcranial magnetic stimulation (TMS) to shed light on the role of the occipital face area (OFA), a key region in face processing, and the lateral occipital (LO) cortex, a key area in object processing, in symmetry detection. In the first experiment, we applied TMS over the rightOFA, its left homolog (leftOFA), rightLO, and vertex (baseline) while participants were discriminating between symmetric and asymmetric dot patterns. Stimulation of rightOFA and rightLO impaired performance, causally implicating these two regions in detection of symmetry in low-level dot configurations. TMS over rightLO but not rightOFA also significantly impaired detection of nonsymmetric shapes defined by collinear Gabor patches, demonstrating that rightOFA responds to symmetry but not to all cues mediating figure-ground segregation. The second experiment showed a causal role for rightOFA but not rightLO in facial symmetry detection. Overall, our results demonstrate that both the rightOFA and rightLO are sensitive to symmetry in dot patterns, whereas only rightOFA is causally involved in facial symmetry detection.

Genotoxicity of Nicotiana tabacum leaves on Helix aspersa.

Tobacco farmers are routinely exposed to complex mixtures of inorganic and organic chemicals present in tobacco leaves. In this study, we examined the genotoxicity of tobacco leaves in the snail Helix aspersa as a measure of the risk to human health. DNA damage was evaluated using the micronucleus test and the Comet assay and the concentration of cytochrome P450 enzymes was estimated. Two groups of snails were studied: one fed on tobacco leaves and one fed on lettuce (Lactuca sativa L) leaves (control group). All of the snails received leaves (tobacco and lettuce leaves were the only food provided) and water ad libitum. Hemolymph cells were collected after 0, 24, 48 and 72 h. The Comet assay and micronucleus test showed that exposure to tobacco leaves for different periods of time caused significant DNA damage. Inhibition of cytochrome P450 enzymes occurred only in the tobacco group. Chemical analysis indicated the presence of the alkaloid nicotine, coumarins, saponins, flavonoids and various metals. These results show that tobacco leaves are genotoxic in H. aspersa and inhibit cytochrome P450 activity, probably through the action of the complex chemical mixture present in the plant.

Cross-adaptation combined with TMS reveals a functional overlap between vision and imagery in the early visual cortex.

The extent to which the generation of mental images draws on the neuronal representations involved in visual perception has been the subject of much debate. To investigate this overlap, we assessed whether adaptation to visual stimuli affects the ability to generate visual mental images; such cross-adaptation would indicate shared neural representations between visual perception and imagery. Mental imagery was tested using a modified version of the clock task, in which subjects are presented with a digital time (e.g. "2.15") and are asked to generate a mental image of the clock hands displaying this time on an empty clock face. Participants were adapted to oriented lines either on the upper or lower side of the clock face prior to the mental image generation. The results showed that mental imagery was impaired when the mental image had to be generated in the adapted region of visual space (Experiment 1). In Experiment 2, we used TMS to determine whether this adaptation effect occurs in the early visual cortex (EVC; V1/V2). Relative to control conditions (No TMS and Vertex TMS), EVC TMS facilitated mental imagery generation when the mental image spatially overlapped with the adapter. Our results thus show that neuronal representations in the EVC which encode (and are suppressed by) visual input play a causal role in visual mental imagery.

The chronometry of symmetry detection in the lateral occipital (LO) cortex.

The lateral occipital cortex (LO) has been shown to code the presence of both vertical and horizontal visual symmetry in dot patterns. However, the specific time window at which LO is causally involved in symmetry encoding has not been investigated. This was assessed using a chronometric transcranial magnetic stimulation (TMS) approach. Participants were presented with a series of dot configurations and instructed to judge whether they were symmetric along the vertical axis or not while receiving a double pulse of TMS over either the right LO (rLO) or the vertex (baseline) at different time windows (ranging from 50 ms to 290 ms from stimulus onset). We found that TMS delivered over the rLO significantly decreased participants' accuracy in discriminating symmetric from non-symmetric patterns when TMS was applied between 130 ms and 250 ms from stimulus onset, suggesting that LO is causally involved in symmetry perception within this time window. These findings confirm and extend prior neuroimaging and ERP evidence by demonstrating not only that LO is causally involved in symmetry encoding but also that its contribution occurs in a relatively large temporal window, at least in tasks requiring fast discrimination of mirror symmetry in briefly (75 ms) presented patterns as in our study.

Melatonin restores zinc levels, activates the Keap1/Nrf2 pathway, and modulates endoplasmic reticular stress and HSP in rats with chronic hepatotoxicity.

BACKGROUND: Melatonin (MLT) is a potent antioxidant molecule that is shown to have a beneficial effect in various pathological situations, due to its action against free radicals. AIM: To evaluate the effect of MLT on carbon tetrachloride (CCl4) induced liver injury in rats in terms of oxidative stress, reticular stress, and cell damage. METHODS: Twenty male Wistar rats (230-250 g) were divided into four groups: Control rats, rats treated with MLT alone, rats treated with CCl4 alone, and rats treated with CCl4 plus MLT. CCl4 was administered as follows: Ten doses every 5 d, ten every 4 d, and seven every 3 d. MLT was administered intraperitoneally at a dose of 20 mg/kg from the 10th wk to the end of the experiment (16th wk). RESULTS: MLT was able to reduce the release of liver enzymes in the bloodstream and to decrease oxidative stress in CCl4 treated rats by decreasing the level of thiobarbituric acid reactive substances and increasing superoxide dismutase activity, with a lower reduction in serum zinc levels, guaranteeing a reduction in liver damage; additionally, it increased the expression of nuclear factor (erythroid-derived 2)-like 2 and decreased the expression of Kelch-like ECH-associated protein 1. MLT also decreased the expression of the proteins associated with endoplasmic reticulum stress, i.e., glucose-regulated protein 78 and activating transcription factor 6, as well as of heat shock factor 1 and heat shock protein 70. CONCLUSION: MLT has a hepatoprotective effect in an experimental model of CCl4-induced liver injury, since it reduces oxidative stress, restores zinc levels, and modulates endoplasmic reticulum stress.

Exposure in the tobacco fields: Genetic damage and oxidative stress in tobacco farmers occupationally exposed during harvest and grading seasons.

Agricultural workers engaged in tobacco cultivation are constantly exposed to large amounts of harmful agents, such as pesticides and nicotine. Furthermore, most of the flue-cured tobacco leaves are manually graded exposing workers to agents such as tobacco-specific nitrosamines. This study aimed to evaluate genetic damage and oxidative stress in tobacco farmers occupationally exposed during the harvest and grading seasons. We obtained data on DNA damage detected in Comet assay in blood cells and micronucleus experiment with buccal cells from 241 individuals. The serum cotinine levels and nitrates were also evaluated. The Comet Assay results showed a showed an increased visual score for males and females during harvest time and tobacco grading. An increase of micronucleated and binucleated cells was observed in the grading group compared to the control and harvest groups. The oxidative stress measurements showed a clear increase of thiobarbituric acid reactive substances (TBARS) in tobacco farmers during harvest time, and trolox equivalent antioxidant capacity (TEAC) in individuals during harvest and grading time compared to the controls. Significant increases of the cotinine levels were observed during the harvest and grading period (harvest>grading), and nitrates for the grading period compared to the control. In this study, tobacco farmers presented compromised DNA integrity associated with enhanced oxidative stress levels.

Role of quercetin in preventing thioacetamide-induced liver injury in rats.

In hepatic toxicity induced in rats by two injections of thioacetamide (TAA, 350 mg/kg with an interval of 8 hr), the action of quercetin was investigated. After 96 hr, TAA administration resulted in hepatic necrosis, significant increases in serum transaminase activity, and increases in hepatic lipoperoxidation. Thioacetamide-induced hepatotoxicity also showed changes in antioxidant enzymes in the liver of rats, with alterations in p-ERK 1/2 (phosphorylated extracellular-signal related kinase 1/2) as well as an imbalance between proapototic protein Bax and anti-apoptotic protein Bcl-2 expression. With administration of the flavonoid quercetin (50 mg/Kg i.p.) for four consecutive days following TAA, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were close to normal values in rats. Histological findings suggested that quercetin had a preventive effect on TAA-induced hepatic necrosis. Quercetin treatment caused significant decreases in lipid peroxide levels in the TAA-treated rats, with some changes in antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Quercetin also inhibited the change of the p-ERK1/2 by TAA and significantly prevented the increase in Bax/Bcl-2 ratio, thus preventing apoptosis. Findings indicate that quercetin may have a preventive effect on TAA-induced hepatotoxicity by modulating the oxidative stress parameters and apoptosis pathway.

Different neural representations for detection of symmetry in dot-patterns and in faces: A state-dependent TMS study.

The occipital face area (OFA) has been shown to code the presence of symmetry in faces and in vertically symmetric dot patterns. However, it is not clear whether symmetry processing of face and non-face stimuli involve overlapping neural mechanisms in OFA. This was assessed using state-dependent TMS by employing a priming paradigm. Specifically, we examined whether prior presentation of low-level symmetry affects the impact of TMS on discrimination of symmetry in subsequently presented faces - indicating that the same neural mechanisms encode symmetry in both face and non-face stimuli. Participants performed a symmetry discrimination task on a series of faces, each of which was preceded by either a vertically symmetric, a horizontally symmetric or a non-symmetric dot configuration (prime) while receiving stimulation over either the right OFA, the right Lateral Occipital Cortex (rLO) or over a control site (Vertex). Vertically symmetric dot patterns primed symmetry discrimination in faces. The key finding was that the priming effect was not affected by TMS applied over OFA; stimulation of this site (but not of rLO) impaired the discrimination of facial symmetry regardless of prime type. Overall, these results suggest that distinct neural representations in OFA are involved in symmetry detection in face and non-face stimuli.

Zinc supplementation reduces diet-induced obesity and improves insulin sensitivity in rats.

Rates of obesity have been growing at alarming rates, compromising the health of the world population. Thus, the search for interventions that address the metabolic repercussions of obesity are necessary. Here we evaluated the metabolic and antioxidant effects of zinc and branched-chain amino acids (BCAA) supplementation on obese rats. Male Wistar rats were fed either a high-fat/high-fructose diet (HFD) or a standard diet (SD) for 19 weeks. From the fifteenth week until the end of the experiment, HFD- and SD-fed rats received zinc (6 mg/kg) or BCAA (750 mg/kg) supplementation. Body weight, abdominal fat, lipid profile, blood glucose, insulin, leptin, and hepatic transaminases were evaluated. In the liver, superoxide dismutase and catalase activities and lipid peroxidation were also analyzed. HFD-fed animals showed increased weight gain, abdominal fat pad, plasma insulin, leptin, and triglycerides levels in comparison with SD-fed rats. Zinc supplementation reduced all these parameters, suggesting a beneficial role for the treatment of obesity. BCAA, on the other hand, did not show any beneficial effect. Liver antioxidant enzymes and hepatic transaminases plasma levels did not change among groups. Lipid peroxidation was higher in HFD-fed rats and was not reverted by zinc or BCAA supplementation. In conclusion, zinc supplementation may be a useful strategy for the treatment of the metabolic dysfunction associated with obesity.

Simvastatin Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in Nonalcoholic Steatohepatitis Experimental Model.

OBJECTIVE: In this study, we evaluated the efficacy of simvastatin in the treatment of nonalcoholic steatohepatitis induced by methionine and choline-deficient diet in mice and its possible effect on factors involved in the pathogenesis of the disease including oxidative stress and endoplasmic reticulum stress. METHOD: Male C57BL6 mice were fed either a normal diet (control) or a methionine and choline-deficient diet for four weeks and then treated orally with simvastatin (4 mg/kg once a day) for two final weeks. At the end of the experimental period, liver integrity, biochemical analysis, hepatic lipids, histology, DNA damage, biomarkers of oxidative stress, and endoplasmic reticulum stress were assessed. RESULTS: Simvastatin treatment was able to significantly reduce hepatic damage enzymes and hepatic lipids and lower the degree of hepatocellular ballooning, without showing genotoxic effects. Simvastatin caused significant decreases in lipid peroxidation, with some changes in antioxidant enzymes superoxide dismutase and glutathione peroxidase. Simvastatin activates antioxidant enzymes via Nrf2 and inhibits endoplasmic reticulum stress in the liver. CONCLUSIONS: In summary, the results provide evidence that in mice with experimental nonalcoholic steatohepatitis induced by a methionine and choline-deficient diet, the reduction of liver damage by simvastatin is associated with attenuated oxidative and endoplasmic reticulum stress.

Oral glutamine supplementation attenuates inflammation and oxidative stress-mediated skeletal muscle protein content degradation in immobilized rats: Role of 70 kDa heat shock protein.

Skeletal muscle disuse results in myofibrillar atrophy and protein degradation, via inflammatory and oxidative stress-mediated NF-kB signaling pathway activation. Nutritional interventions, such as l-glutamine (GLN) supplementation have shown antioxidant properties and cytoprotective effects through the modulation on the 70-kDa heat shock protein (HSP70) expression. However, these GLN-mediated effects on cell signaling pathways and biochemical mechanisms that control the myofibrillar protein content degradation in muscle disuse situations are poorly known yet. This study investigated the effects of oral GLN plus l-alanine (ALA; GLN â€‹+ â€‹ALA-solution) supplementation, either in their free or dipeptide (L-alanyl-l-glutamine-DIP) form, on GLN-glutathione (GSH) axis and cytoprotection mediated by HSP70 protein expression in the slow-twitch soleus and fast-twitch gastrocnemius skeletal muscle of rats submitted to 14-days of hindlimb immobilization-induced disuse muscle atrophy. Forty-eight Wistar rats were distributed into 6 groups: hindlimb immobilized (IMOB group) and hindlimb immobilized orally supplemented with either GLN (1 g kg-1) plus ALA (0.61 g kg-1) â€‹(GLN â€‹+ â€‹ALA-IMOB group) or 1.49 â€‹g â€‹kg-1 of DIP (DIP-IMOB group) and; no-immobilized (CTRL) and no-immobilized supplemented GLN â€‹+ â€‹ALA and DIP baselines groups. All animals, including CTRL and IMOB rats (water), were supplemented via intragastric gavage for 14 days, concomitantly to immobilization period. Plasma and muscle GLN levels, lipid (thiobarbituric acid reactive substances-TBARS) and protein (carbonyl) peroxidation, erythrocyte concentration of reduced GSH and GSH disulfide (GSSG), plasma and muscle pro-inflammatory TNF-α levels, muscle IKKα/ß-NF-kB signaling pathway and, the myofibrillar protein content (MPC) were measured. The MPC was significantly lower in IMOB rats, compared to CTRL, GLN â€‹+ â€‹ALA, and DIP animals (p â€‹< â€‹0.05). This finding was associated with reduced plasma and muscle GLN concentration, equally in IMOB animals. Conversely, both GLN â€‹+ â€‹ALA and DIP supplementation restored plasma and muscle GLN levels, which equilibrated GSH and intracellular redox status (GSSG/GSH ratio) in erythrocytes and skeletal muscle even as, increased muscle HSP70 protein expression; attenuating oxidative stress and TNF-α-mediated NF-kB pathway activation, fact that reverberated on reduction of MPC degradation in GLN â€‹+ â€‹ALA-IMOB and DIP-IMOB animals (p â€‹< â€‹0.05). In conclusion, the findings shown herein support the oral GLN â€‹+ â€‹ALA and DIP supplementations as a therapeutic and effective nutritional alternative to attenuate the deleterious effects of the skeletal muscle protein degradation induced by muscle disuse.

Effect of therapeutic ultrasound on the quadriceps muscle injury in rats - evaluation of oxidative stress and inflammatory process.

Muscle injuries are frequent, both in sports and work, and may be caused by stretching, distension, repetitive effort or bruising. Such lesions can lead to the generation of free radicals, triggering oxidative stress and the release of some inflammatory mediators. Therapeutic ultrasound (UST) is one of the most used electrotherapy resources in the physiotherapist's clinical practice. Our aim was to evaluate the use of therapeutic ultrasound on oxidative stress and inflammatory process in an experimental model of single quadriceps muscle injury in Wistar rats. We used a total of 28 male rats, weighing between 250-300 grams, randomly divided into four groups. In the right quadriceps, a simple impact of contusion was induced by means of a press. The animals were submitted to a daily UST treatment for a total of seven consecutive applications for three minutes each, that started 24 hours after the trauma induction. The results in the Trauma + Therapeutic ultrasound group at TBARS levels and in the enzymatic activity of SOD and GPx presented a significant difference. In the histological analysis of the Trauma + Therapeutic ultrasound group presented a reorganization of the fiber's structure and a reduction of the presence of inflammatory infiltrate. In the results of the immunohistochemistry of iNOS, TNF-α and NF-κB in muscle tissue, we observed that the group treated with ultrasound showed a reduction in the expression of the proteins. The use of UST was effective in protecting muscle tissue from oxidative stress, inflammatory process and in the rearrangement of muscle fibers.

TMS over right OFA affects individuation of faces but not of exemplars of objects.

In addition to its well-documented role in processing of faces, the occipital face area in the right hemisphere (rOFA) may also play a role in identifying specific individuals within a class of objects. Here we explored this issue by using fMRI-guided TMS. In a first experiment, participants had to judge whether two sequentially presented images of faces or objects represented exactly the same exemplar or two different exemplars of the same class, while receiving online TMS over either the rOFA, the right lateral occipital cortex (rLO) or the Vertex (control). We found that, relative to Vertex, stimulation of rOFA impaired individuation of faces only, with no effect on objects; in contrast, TMS over rLO reduced individuation of objects but not of faces. In a second control experiment participants judged whether a picture representing a fragment of a stimulus belonged or not to the subsequently presented image of a whole stimulus (part-whole matching task). Our results showed that rOFA stimulation selectively disrupted performance with faces, whereas performance with objects (but not with faces) was selectively affected by TMS over rLO. Overall, our findings suggest that rOFA does not contribute to discriminate between exemplars of non-face objects.

On the Mechanisms of Transcranial Magnetic Stimulation (TMS): How Brain State and Baseline Performance Level Determine Behavioral Effects of TMS.

The behavioral effects of Transcranial Magnetic Stimulation (TMS) can change qualitatively when stimulation is preceded by initial state manipulations such as priming or adaptation. In addition, baseline performance level of the participant has been shown to play a role in modulating the impact of TMS. Here we examined the link between these two factors. This was done using data from a previous study using a TMS-priming paradigm, in which, at group level, TMS selectively facilitated targets incongruent with the prime while having no statistically significant effects on other prime-target congruencies. Correlation and linear mixed-effects analyses indicated that, for all prime-target congruencies, a significant linear relationship between baseline performance and the magnitude of the induced TMS effect was present: low levels of baseline performance were associated with TMS-induced facilitations and high baseline performance with impairments. Thus as performance level increased, TMS effects turned from facilitation to impairment. The key finding was that priming shifted the transition from facilitatory to disruptive effects for targets incongruent with the prime, such that TMS-induced facilitations were obtained until a higher level of performance than for other prime-target congruencies. Given that brain state manipulations such as priming operate via modulations of neural excitability, this result is consistent with the view that neural excitability, coupled with non-linear neural effects, underlie behavioral effects of TMS.

Protective effects of quercetin treatment in a pristane-induced mouse model of lupus nephritis.

INTRODUCTION: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus. As murine models of LN are valuable tools to better understand its pathophysiology and to search for new effective treatments, we investigated the effects of the bioflavonoid quercetin on pristane-induced LN mice through histomorphological analyses. METHODS: Immunofluorescence and biochemical assays were used to evaluate the expression of markers of inflammation (interleukin-6, IL-6; tumour necrosis factor-α, TNF-α), oxidative stress (catalase, CAT; superoxide dismutase 1, SOD1; thiobarbituric acid reactive substances, TBARS), apoptosis (Bax), and fibrosis (transforming growth factor-ß1, TGF-ß1). Glomerular and tubular ultrastructure was analysed, and tissue messenger RNA of podocin, podoplanin and α3ß1-integrin were quantified using the real-time polymerase chain reaction. RESULTS: Pristane-induced LN mice showed severe kidney injury, characterized by increased proteinuria, glomerular mesangial expansion and inflammation, high expression of the pro-fibrotic, apoptotic and prooxidant markers and reduction of antioxidants. In the kidney ultrastructure, foot process (FP) effacement, apoptotic mesangial cells and abnormal mitochondria with disrupted cristae were observed, along with suppressed tissue mRNA of podocin, podoplanin and α3ß1-integrin. Treatment with quercetin in the pristane-induced LN mice model was nephroprotective, decreasing proteinuria levels and significantly lowering tissue expression of IL-6, TNF-α, TGF-ß1, Bax and TBARS. Simultaneously, quercetin significantly increased CAT and SOD1 expressions in these mice. In addition, it was observed improvement of the kidney ultrastructure, and tissue mRNA of podocin, but not podoplanin and α3ß1-integrin, was restored to the levels found in the control mice. CONCLUSION: In conclusion, these findings provide experimental evidence of the renoprotective effects of quercetin in the pristane-induced LN mice model. We suggest that quercetin effectively ameliorates the kidney damage caused by pristane, a bioflavonoid to be further evaluated as a new therapeutic strategy in this disease.

Effects of remote ischemic preconditioning and topical hypothermia in renal ischemia-reperfusion injury in rats.

PURPOSE: To evaluate whether combining hypothermia and remote ischemic preconditioning (RIPC) results in protection from ischemia-reperfusion (IR). METHODS: Thirty-two Wistar rats underwent right nephrectomy and were randomly assigned to four experimental protocols on the left kidney: warm ischemia (group 1), cold ischemia (group 2), RIPC followed by warm ischemia (group 3), and RIPC followed by cold ischemia (group 4). After 240 minutes of reperfusion, histological changes in the left kidney, as well as lipid peroxidation and antioxidant enzyme activity, were analyzed. The right kidney was used as the control. Serum creatinine was collected before and after the procedures. RESULTS: RIPC combined with hypothermia during IR experiments revealed no differences on interventional groups regarding histological changes (p=0.722). Oxidative stress showed no significant variations among the groups. Lower serum creatinine at the end of the procedure was seen in animals exposed to hypothermia (p<0.001). CONCLUSIONS: Combination of RIPC and local hypothermia provides no renal protection in IR injury. Hypothermia preserves renal function during ischemic events. Furthermore, RIPC followed by warm IR did not show benefits compared to warm IR alone or controls in our experimental protocol.

Antifibrogenic effect of melatonin in rats with experimental liver cirrhosis induced by carbon tetrachloride.

BACKGROUND AND AIM: Liver diseases are a major public health problem, accounting for a significant number of hospital visits and admissions and an increasing mortality rate. Melatonin (MLT) is a powerful antioxidant molecule that has been shown to be beneficial under various conditions. The objective was to evaluate the effect of MLT on experimental liver cirrhosis induced by carbon tetrachloride (CCl4) in rats. METHODS: Twenty male Wistar rats (230-250 g) were divided into four groups. I: control group (CO); II: CO + MLT; III: CCl4; and IV: CCl4 + MLT. CCl4 was administered intraperitoneally (i.p.) as follows: 10 doses every 5 days, 10 doses every 4 days, and 7 doses every 3 days. MLT was administered i.p. at a dose of 20 mg/kg from the 10th week to the end of the experiment (16th week). RESULTS: In the CCl4 + MLT group, we found that MLT caused a decrease in the level of F2-isoprostanes and NQO1 expression. We also found that MLT reduced the inflammatory process as shown by decreased expressions of NF-KB/p65 and inducible nitric oxide synthase (iNOS) and a smaller amount of inflammatory infiltrate. MLT reduced the expression of transforming growth factor beta1 (TGF-ß1), alpha-smooth muscle actin (α-SMA), and vascular endothelial growth factor (VEGF). Picrosirius staining showed that MLT decreases fibrosis. CONCLUSION: MLT has a potent antifibrogenic effect, modulating the parameters of oxidative stress, angiogenesis, and inflammation.

Combined effects of melatonin and topical hypothermia on renal ischemia-reperfusion injury in rats.

PURPOSE: To evaluate whether their combination was more effective than either alone in decreasing renal damage due to ischemia/reperfusion (I/R) injury in rats. METHODS: Thirty-two Wistar rats were assigned to four groups. Following right nephrectomy, their left kidneys were subjected to warm ischemia (IR), cold ischemia (TH+IR), intraperitoneal injection of 10 mg/kg melatonin (MEL+IR), or injection of 10 mg/kg melatonin followed by cold ischemia (MEL+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, left nephrectomy was performed for histopathological evaluation, lipid peroxidation, and measurement of antioxidant enzyme activity. Serum was collected to measure urea and creatinine concentrations. RESULTS: Histopathological damage induced by ischemia and reperfusion was more attenuated in the MEL+TH+IR group than in the MEL+IR and TH+IR groups (p<0.037). Superoxide dismutase activity was significantly higher (p<0.029) and creatinine (p<0.001) and urea (p<0.001) concentrations were significantly lower in the MEL+TH+IR group than in the MEL+IR and TH+IR groups. CONCLUSION: The combination of melatonin (MEL) and topical hypothermia (TH) better protects against renal I/R injury than does MEL or TH alone.

Not all visual symmetry is equal: Partially distinct neural bases for vertical and horizontal symmetry.

Visual mirror symmetry plays an important role in visual perception in both human and animal vision; its importance is reflected in the fact that it can be extracted automatically during early stages of visual processing. However, how this extraction is implemented at the cortical level remains an open question. Given the importance of symmetry in visual perception, one possibility is that there is a network which extracts all types of symmetry irrespective of axis of orientation; alternatively, symmetry along different axes might be encoded by different brain regions, implying that there is no single neural mechanism for symmetry processing. Here we used fMRI-guided transcranial magnetic stimulation (TMS) to compare the neural basis of the two main types of symmetry found in the natural world, vertical and horizontal symmetry. TMS was applied over either right Lateral Occipital Cortex (LO), right Occipital Face Area (OFA) or Vertex while participants were asked to detect symmetry in low-level dot configurations. Whereas detection of vertical symmetry was impaired by TMS over both LO and OFA, detection of horizontal symmetry was delayed by stimulation of LO only. Thus, different types of visual symmetry rely on partially distinct cortical networks.