Alpha-lipoic acid reduces nociception by reducing oxidative stress and neuroinflammation in a model of complex regional pain syndrome type I in mice.

Complex regional pain syndrome type I (CRPS-I) is a disabling pain condition without adequate treatment. Chronic post-ischemia pain injury (CPIP) is a model of CRPS-I that causes allodynia, spontaneous pain, inflammation, vascular injury, and oxidative stress formation. Antioxidants, such as alpha lipoic acid (ALA), have shown a therapeutic potential for CRPS-I pain control. Thus, we aim to evaluate if ALA repeated treatment modulates neuroinflammation in a model of CRPS-I in mice. We used male C57BL/6 mice to induce the CPIP model (O-ring torniquet for 2 h in the hindlimb). For the treatment with ALA or vehicle (Veh) mice were randomly separated in four groups and received 100 mg/kg orally once daily for 15 days (CPIP-ALA, CPIP-Veh, Control-ALA, and Control-Veh). We evaluated different behavioral tests including von Frey (mechanical stimulus), acetone (cold thermal stimulus), rotarod, open field, hind paw edema determination, and nest-building (spontaneous pain behavior). Also, hydrogen peroxide (H2O2) levels, NADPH oxidase and superoxide dismutase (SOD) activity in the sciatic nerve and spinal cord, and Iba1, Nrf2, and Gfap in spinal cord were evaluated at 16 days after CPIP or sham induction. Repeated ALA treatment reduced CPIP-induced mechanical and cold allodynia and restored nest-building capacity without causing locomotor or body weight alteration. ALA treatment reduced SOD and NADPH oxidase activity, and H2O2 production in the spinal cord and sciatic nerve. CPIP-induced neuroinflammation in the spinal cord was associated with astrocyte activation and elevated Nfr2, which were reduced by ALA. ALA repeated treatment prevents nociception by reducing oxidative stress and neuroinflammation in a model of CRPS-I in mice.

Analysis of nuclear maturation, DNA damage and repair gene expression of bovine oocyte and cumulus cells submitted to ionizing radiation.

Radiotherapy causes destruction of tumor cells, but also threatens the integrity and survival of surrounding normal cells. Then, woman submitted to irradiation for cancer treatment may present permanent ovary damage, resulting in impaired fertility. The objective of this study was to investigate the effects of therapeutic doses of ionizing radiation (IR), used for ovarian cancer treatment in humans, on bovine cumulus-oocyte complexes (COCs) as experimental model. Bovine ovaries were exposed to 0.9 Gy, 1.8 Gy, 3.6 Gy or 18.6 Gy IR, and then COCs were collected and used to evaluate: (a) oocyte nuclear maturation; (b) presence of phosphorylated H2A.X (γH2AX), as an indicator of DNA double-strand breaks (DSBs); and (c) expression of genes involved in DNA repair (TP53BP1, RAD52, ATM, XRCC6 and XRCC5) and apoptosis (BAX). The radiation doses tested in this study had no detrimental effects on nuclear maturation and did not increase γH2AX in the oocytes. However, IR treatment altered the mRNA abundance of RAD52 (RAD52 homolog, DNA repair protein) and BAX (BCL2-associated X protein). We conclude that although IR doses had no apparent effect on oocyte nuclear maturation and DNA damage, molecular pathways involved in DNA repair and apoptosis were affected by IR exposure in cumulus cells.

Effect of Adding Matricaria recutita L., Cymbopogon citratus, or Mentha piperita L. Extracts to Fermented Orange Beverage: Sensory Evaluation, Physicochemical Characterization, and Prediction of Toxic Risks and Biological Activity In Silico.

Fermentation is an important tool in producing functional beverages through agro-industrial wastes, and medicinal and aromatic plants due to the specific content of bioactive molecules. Therefore, this study evaluated the contribution of Matricaria recutita (chamomile), Cymbopogon citratus (lemongrass), or Mentha piperita (peppermint) extracts to the phytochemical profile and potential biological effects of a functional fermented orange beverage in vitro and in silico. The concentrations of aromatic herbal extracts that yielded the best sensory performance for fermented beverages were selected for analyses that involved characterizing the fermented beverages. The beverages that received the extracts (2%) had the highest phenolic and flavonoid content and antioxidant potential compared to the control. Hesperidin (124-130 mg L-1), narirutin (66-70 mg L-1), chlorogenic (11-16 mg L-1), caffeic (5.3-5.5 mg L-1), and ferulic (1-1.7 mg L-1) acids were found in the different formulations. The in silico analysis suggested that the evaluated compounds do not present a toxicity risk (mutagenicity, carcinogenicity, hepatotoxicity, and ability to penetrate the blood-brain barrier). Additionally, they can contribute to the biological effects of therapeutic importance, such as antioxidant, gastroprotective, and anti-ulcerative properties, and the Mentha piperita L. extract presented the greatest potential among the evaluated herbs for use in functional fermented beverages.

Phytochemical characterisation, antioxidant capacity, and in vitro toxicity of Richardia brasiliensis gomes crude extracts.

Richardia brasiliensis is a species used in folk medicine and rich in active compounds. In this study, the extracts were submitted to UHPLC-ESI-MS/MS analysis and total polyphenols, tannins, and flavonoids assays. Besides, it was determined its antioxidant capacity, oxidative stress markers and toxicological profile. Fourteen polyphenols were found and, in the dosages, a slight change in the concentrations in each extract was observed. Regarding the antioxidant capacity, the responses were different in the methods used. There was an increase in lipid peroxidation, and NO, however total ROS remained unchanged. The cells remained more than 90% viable and the extracts did not cause damage to single strands of DNA, with the exception of the crude autumn and spring extracts at 500 µg/mL. The results found in this study suggest that extracts are potentially toxic to human leukocyte cells in high concentrations; however, more studies should be performed in different cell lines.

Caffeic acid and ferulic acid can improve toxicological damage caused by iron overload mediated by carbonic anhydrase inhibition.

The iron ion is an essential element for most forms of life, however, it can damage biological systems when found in free form. Chelation therapy is very important, but it is precarious. Caffeic and ferulic acid are antioxidant compounds with many properties described in research such as anti-inflammatory, antiobesogenic, antithrombotic, vasodilator, and anti-tumor. The aim of the study was to evaluate presenting an in silico approach on the toxicity and bioavailability of caffeic and ferulic acid, subsequently, evaluating them in an iron overload model in vivo and providing a pharmacophoric model through molecular docking. The predictive in silico test did not show relevant toxicity of the compounds, therefore, the in vivo test was performed. The rats received dextran iron and the test groups received caffeic and ferulic acid orally for six weeks. Biochemical, hematological parameters, and tissue oxidative stress marker were analyzed. The experimental model showed increased serum iron levels and changes in several serum parameters such as glucose (215.8 ± 20.3 mg/dL), ALT (512.2 ± 128.7 U/L), creatine kinase (186.8 ± 30.1 U/L), and creatine kinase isoform MB (373.3 ± 69.7 U/L). Caffeic acid and, to a lessed degree, ferullic acid, attenuated the effects of iron overload on the rat serum biochemical parameters. Docking showed a pharmacophoric model where carbonic anhydrase interacted with the test molecules and caffeic acid showed less energy expenditure in this interaction. The results illustrate a new therapeutic action of phenolic compounds on iron overload. The possible interference of carbonic anhydrase in iron metabolism needs to be elucidated.

Tucumã (Astrocaryum aculeatum) extract: phytochemical characterization, acute and subacute oral toxicity studies in Wistar rats.

Natural products are often used by the population to treat and/or prevent several disorders. Tucumã is an Amazonian fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. Therefore, the phytochemical characterization, acute and repeated dose 28-day oral toxicities of crude extract of tucumã's pulp (CETP) in Wistar rats were evaluated. For the CETP preparation, tucumã pulp was crushed and placed into sealed amber glass jars containing absolute ethanol solution for extraction. CETP phytochemical analyses evidenced the presence of carotenoids, flavonoids, unsaturated and satured fatty acids, and triterpenes. In the acute toxicity, female rats from the test group were treated with CETP at single dose of 2000 mg/kg. For the repeated dose toxicity, CETP was administered to male and female rats at doses of 200, 400 and 600 mg/kg, for 28 days. Body weight was recorded during the experiment and blood, liver and kidney were collected for further analysis. No mortality or toxicity signs were observed during the studies. CETP was classified as safe (category 5, OECD guide), in acute toxicity. In repeated dose study was observed alterations in some biochemical parameters, as well as in oxidative damage and enzymatic activity. Histopathological findings showed renal damage in male rats at higher dose. The data obtained suggest that CETP did not induced toxicity after exposure to a single or repeated doses in female rats. However, in males may be considered safe when given repeatedly in low doses.

Randia ferox (Cham & Schltdl) DC.: phytochemical composition, in vitro cyto- and genotoxicity analyses.

Randia ferox is a Brazilian native species used in folk medicine. Scientific information regarding the toxicology and phytochemistry of this plant remains unclear. We aimed to produce a R. ferox extract, identify its chemical matrix, and evaluate its safety profile. The extract chemical composition was accessed through UHPLC-MS/MS. Mononuclear cells, erythrocytes, fibroblasts, macrophages, and kidney cells were subjected to extract concentration-response curve testing. The cellular viability, proliferation, dsDNA release, reactive oxygen species (ROS), nitric oxide (NO), hemolysis, and DNA damage were determined. Ten molecules were found in the extract matrix. Most of the tested concentrations can be considered safe. Cellular viability, proliferation, dsDNA release, and NO remained at similar levels to the control. The extract increased ROS in macrophages. None of the tested concentrations induced DNA damage or hemolysis. The data suggest R. ferox extract contains several bioactive molecules and has a safety profile in vitro.

In silico and in vivo protective effect of Morus nigra leaves on oxidative damage induced by iron overload.

Morus nigra L. is a plant popularly known as 'amoreira preta', very used in folk medicine. Iron overload (hemochromatosis) is a clinical condition that causes damage to various tissues due to oxidative stress. Therapy to control iron overload is still unsatisfactory. The protective effect on oxidative stress induced by iron overload was verified. Phytochemical characterization was evaluated by UHPLC-MS/MS. The in silico toxicity predictions of the main phytochemicals were performed via computer simulation. To induce iron overload, the animals received iron dextran (50 mg/kg/day). The test groups received doses of 500 and 1000 mg/kg of M. nigra extract for six weeks. Body weight, organosomatic index, serum iron, hepatic markers, cytokines, interfering factors in iron metabolism, enzymatic and histopathological evaluations were analyzed. Vanillic acid, caffeic acid, 6-hydroxycoumarin, p-coumaric acid, ferulic acid, rutin, quercitrin, resveratrol, apigenin and kaempferol were identified in the extract. In addition, in silico toxic predictions showed that the main compounds presented a low probability of toxic risk. The extract of M. nigra showed to control the mediators of inflammation and to reduce iron overload in several tissues. Our findings illustrate a novel therapeutic action of M. nigra leaves on hemochromatosis caused by iron overload.

Hydroalcoholic extract of leaf of Arachis hypogaea L. (Fabaceae) did not induce toxic effects in the repeated-dose toxicity study in rats.

Arachis hypogaea L. (peanut) leaf is traditionally used for the treatment of insomnia in Asia. However, studies describing the safety and toxicity profile for this plant preparation are limited. Thus, the goal of this study was to investigate the toxicity of peanut leaf hydroalcoholic extract (PLHE) repeated treatment. The extract was administered orally (100, 300 or 1000 mg/kg) in male and female Wistar rats for 28 days (OECD guideline 407). PLHE treatment did not cause mortality or weight variation in the animals. Also, there was no alteration on locomotor activity (open field test), motor coordination (rotarod test), or anxiety behaviour (elevated plus-maze test). Male rats had a reduction in relative liver weight (100 mg/kg) and an increase in total kidney weight (1000 mg/kg), but there was no change in biochemical and haematological parameters after PLHE treatment. Free extracellular double-stranded DNA (dsDNA) levels was also evaluated, but PLHE treatment did not increase this parameter in rat organs. Also, the dose of 1000 mg/kg of PLHE significantly increased the total thiols in the liver of females compared with the control animals. Thus, PLHE did not induce toxicity after repeated exposure for 28 days in rats.

Casearia decandra leaves present anti-inflammatory efficacy in a skin inflammation model in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia decandra (guaçatonga) is popularly used as an anti-inflammatory. We investigated the antioxidant and anti-inflammatory effect of C.decandra leaves (CdE) ethanolic extract and of the rutin standard (present in the CdE). MATERIALS AND METHODS: Male adult Swiss mice were used (25-30 g; 5-6 animals by a group). CdE phytochemical analysis was performed by HPLC method. The antioxidant potential of CdE and rutin was assessed by different methods. Topical anti-inflammatory effect of CdE (0.001-1mg/ear) and rutin (0.003-0.03mg/ear) was evaluated by ear edema formation and inflammatory cells infiltration (MPO activity and histology) on a skin inflammation model induced by topical application of croton oil (1mg/ear). RESULTS: Rutin (27.81 ± 1.11 mg/g) was identified in CdE by HPLC analysis. The required amounts of CdE, rutin and ascorbic acid to reduce the initial concentration of radical DPPH by 50% (IC50) were 7.77 (6.31-9.57) µg/mL, 3.62 (3.26-4.01) µg/mL and 3.74 (3.37-4.14) µg/mL with a radical DPPH reduction of 91 ± 1.2%, 91 ± 0.5%, and 96 ± 0.44% (at 30 µg/mL), respectively. Moreover, CdE and rutin presented H2O2 scavenging activity with H2O2 levels reduction of 41 ± 7% and 46 ± 6%, respectively and SOD-like activity of 60 ± 4% and 51 ± 14%, respectively. On the other hand, just rutin presented nitric oxide scavenging activity of 54 ± 6%. CdE and rutin topically applied inhibited the ear edema with a maximum inhibition of 70 ± 5% (1 mg/ear) and 78 ± 10% (0.03 mg/ear), respectively. Treatments reduced the MPO activity (42 ± 4% to CdE; 1mg/ear and 30 ± 8% to rutin; 0.03 mg/ear). Histologically, the topical treatments also reduced the dermis thickness and the inflammatory cells infiltration. CONCLUSION: We demonstrated the antioxidant and anti-inflammatory effect of C.decandra leaves and rutin. Its antioxidant potential may contribute to inflammatory process attenuation, supporting the C.decandra leaves used as a promising alternative in the therapy of the inflammatory diseases.

Antidiabetic effects of Olea europaea L. leaves in diabetic rats induced by high-fat diet and low-dose streptozotocin.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance, and dyslipidemia. It has broad occurrence worldwide, affecting millions of people, and can cause serious complications. The olive (Olea europaea L.) has important pharmacological functions, including anti-inflammatory, antioxidant, and hypoglycemic activities. Olive leaves are used in traditional medicine for diabetes and hypertension. AIM OF THE STUDY: To evaluate the effect of the ethanolic extract of olive leaves (EEOL) on the metabolism of rats with diabetes induced by a high-fat diet and low dose of streptozotocin (STZ). MATERIALS AND METHODS: Male Wistar rats were either given normal feed or a high-fat diet (70% standard laboratory feed, 15% sucrose, 10% lard and 5% yolk powder) for four weeks, followed by administration of STZ (35 mg/kg, via ip). Animals with fasting glucose levels above 200 mg/dL were considered diabetic. Animals were divided into 5 groups, which received ethanol (10 mL/kg), metformin (250 mg/kg), or EEOL at doses of 200 and 400 mg/kg during 10 weeks by oral gavage. Blood samples were used to measure hematological and biochemical parameters, and kidneys were removed for posterior analysis. Body weight was recorded weekly. RESULTS: A significant decrease in body weight was observed among diabetic animals treated with ethanol and EEOL compared to the control group. Moreover, animals treated with EEOL showed an improvement in glucose levels and in levels of inflammatory and metabolic markers when compared to diabetic animals. CONCLUSIONS: The results indicate a potential anti-diabetic activity of olive leaves, however more studies are needed to validate clinical effects.

In vitro antimicrobial and antimycobacterial activity and HPLC-DAD screening of phenolics from Chenopodium ambrosioides L

Abstract The main objective of this study was to demonstrate the antimicrobial potential of the crude extract and fractions of Chenopodium ambrosioides L., popularly known as Santa-Maria herb, against microorganisms of clinical interest by the microdilution technique, and also to show the chromatographic profile of the phenolic compounds in the species. The Phytochemical screening revealed the presence of cardiotonic, anthraquinone, alkaloids, tannins and flavonoids. The analysis by HPLC-DAD revealed the presence of rutin in the crude extract (12.5 ± 0.20 mg/g), ethyl acetate (16.5 ± 0.37 mg/g) and n-butanol (8.85 ± 0.11 mg/g), whereas quercetin and chrysin were quantified in chloroform fraction (1.95 ± 0.04 and 1.04 ± 0.01 mg/g), respectively. The most promising results were obtained with the ethyl acetate fraction, which inhibited a greater number of microorganisms and presented the lowest values of MIC against Staphylococcus aureus and Enterococcus faecalis (MIC = 0.42 mg/mL), Pseudomonas aeruginosa (MIC = 34.37 mg/mL), Paenibacillus apiarus (MIC = 4.29 mg/mL) and Paenibacillus thiaminolyticus (MIC = 4.29 mg/mL). Considering mycobacterial inhibition, the best results were obtained by chloroform fraction against M. tuberculosis, M. smegmatis, and M. avium (MIC ranging from 156.25 to 625 µg/mL). This study proves, in part, that the popular use of C. ambrosioides L. can be an effective and sustainable alternative for the prevention and treatment of diseases caused by various infectious agents.

Safety assessment of ethanolic extract of Olea europaea L. leaves after acute and subacute administration to Wistar rats.

Olea europaea L., popularly known as olive, is a plant widely used worldwide. Its leaves, fruit and oil are extensively consumed and present important pharmacological properties. However, studies regarding the toxicity of olive leaves are still limited in the literature. Therefore, the aim of the study was to investigate acute and subacute oral toxicities of the ethanolic extract of olive leaves (EEO) in Wistar rats through histopathology and biochemical and hematological parameters. Acute toxicity was assessed using a single dose of 2000 mg/kg of EEO administered by oral gavage to male and female rats. To assess subacute toxicity, EEO was administered during 28 days at different doses (100, 200 and 400 mg/kg) to male and female rats. At the end of the experiments, the liver and kidney were removed and examined microscopically, and blood was collected for hematological and biochemical parameters. A single dose of 2000 mg/kg did not induce mortality or any signs of toxicity among the animals treated. Animals exposed to EEO during 28 days did not present sign of abnormalities. Results demonstrated that EEO did not induce toxicity after exposure to single and repeated doses. However, more studies are needed to fully understand implications for human safety.

The in vitro radiosensitizer potential of resveratrol on MCF-7 breast cancer cells.

Radiation therapy is commonly applied in breast cancer (BC) patients. However, radioresistance and side effects are limiting factors of this practice. Therefore, studying substances that can enhance the radiation effect and, at the same time, protect normal cells is very relevant. Thus, the aim of this work was to assess the radiosensitizer effect of resveratrol (RV) on BC cells (MCF-7). A high cytotoxic and antiproliferative effect was observed in the treatment with 10 µM of RV + 3 Gy ionizing radiation (IR). Our results indicate that, 24 h after the exposition of cell cultures to RV + IR, an induction of necrosis/senescence has occurred. Furthermore, was observed the activation of extrinsic apoptosis pathway through a decrease of the Bax/Bcl-2 ratio and a high activity of caspase 8. Moreover, our data show that this treatment affected the oxidative cell metabolism, increasing oxidative protein, lipid and membrane damage and also acted to decrease the antioxidant enzymes activity. The antiproliferative effect on 72 h cultures may be associated with a high expression of p53 and an interruption of cell cycle in the S phase. Therefore, our results suggest that RV is a potential radiosensitizer of MCF-7 BC cells.

In vitro antimicrobial and antimycobacterial activity and HPLC-DAD screening of phenolics from Chenopodium ambrosioides L.

The main objective of this study was to demonstrate the antimicrobial potential of the crude extract and fractions of Chenopodium ambrosioides L., popularly known as Santa-Maria herb, against microorganisms of clinical interest by the microdilution technique, and also to show the chromatographic profile of the phenolic compounds in the species. The Phytochemical screening revealed the presence of cardiotonic, anthraquinone, alkaloids, tannins and flavonoids. The analysis by HPLC-DAD revealed the presence of rutin in the crude extract (12.5±0.20mg/g), ethyl acetate (16.5±0.37mg/g) and n-butanol (8.85±0.11mg/g), whereas quercetin and chrysin were quantified in chloroform fraction (1.95±0.04 and 1.04±0.01mg/g), respectively. The most promising results were obtained with the ethyl acetate fraction, which inhibited a greater number of microorganisms and presented the lowest values of MIC against Staphylococcus aureus and Enterococcus faecalis (MIC=0.42mg/mL), Pseudomonas aeruginosa (MIC=34.37mg/mL), Paenibacillus apiarus (MIC=4.29mg/mL) and Paenibacillus thiaminolyticus (MIC=4.29mg/mL). Considering mycobacterial inhibition, the best results were obtained by chloroform fraction against M. tuberculosis, M. smegmatis, and M. avium (MIC ranging from 156.25 to 625µg/mL). This study proves, in part, that the popular use of C. ambrosioides L. can be an effective and sustainable alternative for the prevention and treatment of diseases caused by various infectious agents.

Trans-resveratrol reduces cardiac oxidative stress in rats exposed to cigarette smoke / O trans-resveratrol reduz o estresse oxidativo cardíaco de ratos expostos à fumaça de cigarro

Differences between reactive oxygen species and antioxidant defense system unbalance the redox status. The exposure to cigarette smoke can increase this imbalance. Trans-resveratrol is a polyphenol with great antioxidant action that reduces the oxidative stress. This study investigated the effect of the trans-resveratrol supplementation on the cardiac oxidative stress in rats exposed to cigarette smoke. Male Wistar rats were randomized into four groups: Control Group (CG), Exposure to Smoke Group (ESG), Antioxidant Group (AG) and Exposure to Smoke plus Antioxidant Group (ESAG). Animals were exposed to cigarette smoke and supplemented with trans-resveratrol (6.0 mg kg-1) for two months. The lipid peroxidation (TBARS) and the enzymatic activity of catalase (CAT) were measured in the cardiac muscle. The ESG presented the highest lipid peroxidation level compared with CG (p < 0.001), AG (p < 0.001) and ESAG (p < 0.006). The CAT activity was higher in the AG (p < 0.001) and ESAG (p < 0.001) compared with CG. The ESG presented lower CAT activity compared with the ESAG (p < 0.001). The supplementation of Trans-resveratrol attenuated the cardiac oxidative stress and increased the activity of catalase. Our findings evidenced the cardioprotective effect of trans-resveratrol in rats exposed to cigarette smoke.

Diferenças entre espécies reativas de oxigênio e sistema de defesa antioxidante desequilibram o estado redox. Exposição à fumaça de cigarro pode aumentar esse desequilíbrio. Trans-resveratrol é um polifenol com ação antioxidante que reduz o estresse oxidativo. O objetivo do presente estudo foi investigar os efeitos da suplementação com trans-resveratrol no estresse oxidativo cardíaco de ratos expostos à fumaça de cigarro. Randomização de 32 ratos Wistar machos em quatro grupos: Controle (CG), Exposição à Fumaça (ESG), Antioxidante (AG) e Exposição à Fumaça+Antioxidante (ESAG). Animais foram expostos à fumaça de cigarro e suplementados trans-resveratrol (6,0 mg kg-1) durante dois meses. Lipoperoxidação (TBARS) e atividade enzimática da catalase (CAT) foram mensuradas no músculo cardíaco. ESG apresentou maiores níveis de lipoperoxidação quando comparado ao CG (p < 0,001), AG (p < 0,001) e ao ESAG (p < 0,006). Atividade da CAT foi maior no AG (p < 0,001) e no ESAG (p < 0,001) quando comparados ao CG. ESG apresentou a menor atividade da CAT quando comparado ao ESAG (p < 0,001). A suplementação com trans-resveratrol atenuou o estresse oxidativo cardíaco e aumentou a atividade enzimática de defesa catalase. Esses resultados sugerem evidências de efeitos cardioprotetores do trans-resveratrol em ratos expostos à fumaça de cigarro.

Effects of quercetin on polychlorinated biphenyls-induced liver injury in rats / Efecto de la quercetina sobre la lesión hepática inducida por bifenilos policlorados en ratas

Introduction: Polychlorinated biphenyls (PCBs), used as pesticides in agriculture, can lead to irreversible injuries in living organisms, particularly in liver. Oxidative stress has been implicated in the liver pathogenesis induced by different molecules, including PCBs. It has been demonstrated that quercetin, an antioxidant flavonoid found in the diet, exhibits a potent antioxidant effect in different liver pathologies. Objective: To evaluate oxidative stress caused by PCBs in liver and the antioxidant activity of quercetin. Methodology: We used male Wistar rats (n = 36), divided in 4 groups: control, quercetin (50 mg/kg/day), PCBs (0.4 ml/kg/day), and rats treated with both PCBs and quercetin. On day 25 blood was collected to assess liver integrity (enzymes AST, ALT and ALP), and liver samples to measure oxidative stress (TBARS), activity of antioxidant enzymes (SOD, CAT, GPx) and DNA damage (micronucleus assay), and histological damage. Results: TBARS concentration and SOD activity were significantly higher in PCBs animals as compared to the PCB group receiving quercetin. CAT and GPx decreased in PCBs and increased when quercetin was added. The histological analysis showed damage to hepatocytes in PCBs, but quercetin was able to afford protection against such damage. The micronucleus test showed there was an increase in the production of microclenucleus compared to control, and quercetin was able to reduce this effect. Conclusion: Contamination with PCBs led to increased lipid peroxidation and DNA damage, and the use of antioxidant quercetin was effective in reducing PCBs-induced liver injury (AU)

Introducción: los bifenilospoliclonados (PCBs) son pesticidas ampliamente usados en agricultura que pueden inducir daños irreversibles particularmente en el hígado. El estrés oxidativo ha sido implicado en diversas patogénesis hepáticas, incluidas las relacionadas conPCBs. La quercetina, un flavonoide de la dieta, ha demostrado tener un potente efecto antioxidante en diversos modelos de patología hepática. Objetivo: Evaluar el estrés oxidativo hepático inducido por PCBs y la actividad antioxidante de la quercetina. Metodología: Se usaron ratas macho de raza Wistar (n = 36), divididas en cuatro grupos: control, quercetina (50 mg/kg/día), PCBs (0,4 ml/kg/día) y ratas tratadas tanto con PCBs como con quercetina. Transcurridos 25 días de tratamiento se recogieron muestras de sangre, para evaluar la integridad hepática (AST, ALT y ALP), y de tejido para cuantificar el estrés oxidativo (TBARS), actividad antioxidante (SOD, CAT, GPx), daño al DNA (ensayo de micronúcleos) y daño histológico. Resultados: la concentración de TBARS y la actividad SOD fueron significativamente mayores en los animales que recibieron PCBs que en los que recibían quercetina. La actividad de CAT y GPx se redujo con los PCBs y se incrementó al administrar quercetina. Los análisis histológicos y de micronúcleos mostraron daño hepático y al DNA respectivamente inducido por PCBs que eran revertidos con el tratamiento con quercetina. Conclusion: La contaminación con PCBs induce un incremento en la peroxidación lipídica, modificación en la actividad de enzimas antioxidantes, daño histológico y al DNA en el hígado, siendo el antioxidante quercetina es capaz de reducir dichos cambios (AU)

Estudo da emissão de luz por diodoinfravermelho na dor neuropática em ratos / Study of infrared light emitting diodes infraredon neuropathic pain in rats

Introdução: A lesão nervosa periférica pode causar alteraçõesfuncionais tanto sensitivas quanto motoras, podendo promoverimportantes comprometimentos, especialmente a dor neuropática.Dentre os vários tratamentos propostos está o emprego da luz monocromáticade baixa intensidade, como o diodo de emissão de luz(LED). Objetivo: Avaliar o efeito analgésico do LED no espectroinfravermelho em modelo experimental de dor neuropática porconstrição do nervo ciático em ratos. Material e métodos: Foramutilizados 24 ratos machos Wistar, randomizados em 4 grupos (n =6). Grupo I: animais neuropáticos e tratados com LED; grupo II:animais neuropáticos e tratados com o LED desligado (placebo);grupo III: animais Sham e tratados com LED; grupo IV: animaisSham e tratados com LED desligado (placebo). Para avaliar a eficáciado tratamento, foram empregados parâmetros de nocicepção comoalodínia mecânica estática, dinâmica e térmica ao frio; hiperalgesiatérmica ao calor e nocicepção espontânea. Resultados: Os animaisneuropáticos desenvolveram alodínia e hiperalgesia ao estímulomecânico, térmico e nocicepção espontânea em 7 dias (Tempo 0)contados a partir da indução da neuropatia, mantendo essas manifestaçõesaté o 14º dia. Conclusão: O tratamento contínuo com LED noespectro infravermelho promoveu efeito analgésico em um modeloexperimental de dor neuropática em ratos. Os resultados obtidosneste estudo sugerem que esse recurso físico pode ser utilizado notratamento de pacientes com dor neuropática.

Introduction: The peripheral nerve injury can cause sensory andmotor functional changes, promoting important damages, especiallyneuropathic pain. The use of monochromatic light of low intensity,such as light-emitting diode (LED) is among different treatmentsoptions. Objective: This study proposes an evaluation of analgesiceffect of LED in the infrared spectrum in experimental model ofneuropathic pain induced by constriction of the sciatic nerve in rats.Methods: We used 24 male Wistar rats randomized into 4 groups (n= 6). Group I: neuropathic animals, treated with LED; group II:neuropathic animals, treated with LED (placebo); group III: Shamanimals treated with LED, group IV: Sham animals treated withLED turned off (placebo). We used nociception parameters suchas static mechanical allodynia, thermal (cold) dynamics, thermal(heat) hyperalgesia and spontaneous nociceptive in order to evaluatetreatment efficacy. Results: All animals developed neuropathicallodynia and hyperalgesia to mechanical stimulation, thermal andspontaneous nociception in 7 days (time 0), starting on inductionof neuropathy, maintaining these conditions until the 14th day.Conclusion: Continuous LED treatment with infrared spectrumpromotes analgesic effect in experimental model of neuropathic painin rats. The results of this study suggest that this treatment may beused to treat patients with neuropathic pain.