Whey Protein, Vitamins C and E Decrease Interleukin-10 in Chronic Hemodialysis Patients: A Pioneer, Randomized, Double-Blind Pilot Trial.

OBJECTIVE: To evaluate the effects of supplementation with whey protein combined with vitamins C and E on inflammatory markers in hemodialysis (HD) patients. DESIGN AND METHODS: This was a pioneer, randomized and double-blinded study. Patients were randomized into two groups and stratified by HD frequency. The supplementation group received 20 g of whey protein, 250 mg of vitamin C, and 600 IU of vitamin E; the placebo group, 20 g of rice flour, and microcrystalline cellulose capsules. The interventions were given after HD, 3 times a week, for 8 weeks. The inflammatory markers were assessed: interleukin (IL) IL-12p70, IL-10, IL-6, IL-8, and tumor necrosis factor alpha. For statistical analysis, the χ2 test, Student's t-test, Mann-Whitney test, analysis of variance for repeated two-way measurements, paired t test, and Wilcoxon test were performed. P < .05 was considered statistically significant. RESULTS: Twenty-three patients completed the study. No significant differences were found in inflammatory markers when comparing the groups postintervention. In the intragroup was a decrease in IL-10 in the supplementation group after 8 weeks (P = .0382). IL-6 tended to decrease by 810.95% in the supplementation group and increased by 732.8% (nonsignificant) in the placebo group. CONCLUSION: Whey protein combined with vitamins C and E significantly reduced IL-10 in the supplementation group and could be beneficial to reduce IL-6 in HD patients. Future studies are suggested with a larger sample size, different supplementation doses, and longer interventions.

In Vitro Free Radical Scavenging Properties and Anti-Inflammatory Activity of Ilex paraguariensis (Maté) and the Ability of Its Major Chemical Markers to Inhibit the Production of Proinflammatory Mediators.

Ilex paraguariensis A. St. Hil. (Aquifoliaceae), popularly known as "yerba mate," has great economic and social significance for the population of Southern Latin America. This study was conducted (1) to investigate the phytochemical composition of four different standardized extracts, (2) to investigate its free radical scavenging properties, and (3) to investigate the anti-inflammatory action of I. paraguariensis and its major chemical markers. The chemical profile was achieved by Folin-Ciocalteu, by LC/DAD, and by LC/MS assays, while the antioxidant and anti-inflammatory properties were investigated, respectively, by DPPH assay and by inhibition of nitric oxide (Griess reaction) and TNF-α (ELISA). Our results demonstrated that the IA (aqueous infusion extract) showed higher amounts of total phenolic contents (266.62 ± 10.85 mg CAE·g-1 DE), the highest amounts of all six chemical markers (theobromine, 5-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 3-O-caffeoylquinic acid, caffeine, and rutin), and stronger antioxidant activity (EC50 = 54.4 ± 5.14 µg · mL-1). The IA extract also showed the lowest inhibition of NOx secretion (50.10 ± 8.97%) as well as inhibition of TNF-α (83.33 ± 4.01%). Regarding the chemical markers, all compounds showed strong inhibition of NOx secretion, especially theobromine, which was 200x more potent than dexamethasone. Furthermore, TNF-α secretion was also significantly decreased by THEO at 0.033 µM (22.15 ± 6.49%), NCA at 1.97 µM (27.46 ± 3.98%), CCA at 0.35 µM (39.76 ± 5.73%), CGA at 0.56 µM (23.58 ± 5.79%), CAF at 0.52 µM (26.45 ± 5.34%), and RUT at 0.16 µM (40.18 ± 3.70%). Our results suggest that I. paraguariensis and its major chemical markers have strong free radical scavenging properties as well as showed important anti-inflammatory activity and that these compounds in a plant extract may work based on several different mechanisms synergistically, resulting in moderating the immune system.

Antioxidant and anti-inflammatory action (in vivo and in vitro) from the trunk barks of Cabreúva (Myrocarpus frondosus Allemao, Fabaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Myrocarpus frondosus, known as cabreúva, is a tree whose trunk barks are used in folk medicine as tea, syrup, ointments, and tinctures for the treatment of inflammation. However, there is no scientific evidence demonstrating this activity. AIM OF THE STUDY: The present investigation was focused on evaluating the antioxidant and anti-inflammatory activities of M. frondosus, using the in vitro model of RAW 264.7 macrophages induced by LPS and the in vivo model of mouse pleurisy induced by carrageenan. MATERIALS AND METHODS: M. frondosus trunk barks were dried at room temperature for seven days and subjected to exhaustive maceration with ethanol (70%) to obtain its crude extract (CE). CE was subjected to UPLC-HRMS analysis to establish its chemical profile. Its antioxidant activity was evaluated using the DPPH method, reducing power by the iron (III) to iron (II) reduction assay and the ß-carotene-linoleic acid bleaching assay. The RAW 264.7 macrophages were pretreated with the CE in a non-cytotoxic concentration and induced by LPS (1 µg/mL). After 24 h, using the supernatant, we evaluated the nitric oxide (NOx) and interleukin-6 (IL-6) levels. The anti-inflammatory effects of CE (at doses of 30, 100 and 300 mg/kg) were evaluated on leukocyte migration (total and differential), exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, NOx, tumor necrosis factor-α (TNF-α), and IL-6 levels, by using a murine model of neutrophilic inflammation. RESULTS: The UPLC-HRMS of CE revealed the presence of isoflavonones, including biochanin A and formononetin. CE exhibited good antioxidant activity by quenching and decreasing free radicals, as well as reducing pro-oxidant metals. CE did not show cytotoxicity at a concentration below 11 µg/mL and reduced the secretion of the pro-inflammatory NOx in the inflamed macrophages. In vivo assay revealed that CE caused a pronounced inhibition on leukocyte migration, and this inhibition was due to its ability to reduce neutrophil migration. Moreover, CE was also able to reduce the release of critical pro-inflammatory mediators such as MPO, NOx, TNF-α, and IL-6. CONCLUSIONS: All these findings indicate that M. frondosus exhibited antioxidant activity and anti-inflammatory effect.

Anti-Inflammatory Profile of Jungia sellowii Less. by Downregulation of Proinflammatory Mediators and Inhibition of NF-κB and p38 Pathways.

Jungia sellowii Less. (Asteraceae) is a native plant found in Southeast Brazil used traditionally to treat inflammatory diseases. This study was conducted (1) to investigate the toxicity of the crude extract (CE) and (2) to investigate the mechanism of the anti-inflammatory action of J. sellowii L. roots. The potential acute toxicity of CE was performed by administration of only different doses of CE (500, 1,000, and 2,000 i.p.) on mice for 14 days. The anti-inflammatory effect was evaluated using carrageenan-induced acute pleural cavity inflammation in a mouse model, evaluated through the following inflammatory variables: leukocyte, protein concentrations of the exudate, myeloperoxidase (MPO), adenosine deaminase (ADA), nitric oxide metabolites (NOx), and proinflammatory cytokine (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin- (IL-) 6, and IL-12) levels in mouse pleural fluid leakage. The p65 protein phosphorylation of nuclear factor NF-kappa B (p65 NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation were analyzed in lung tissue. Our results demonstrated that the administration of CE up to 2,000 mg/kg did not present a toxic effect. In addition, the pretreatment of mice with CE; its derived fractions (aqueous fraction (AqF), butanol fraction (BuOHF), and ethyl acetate fraction (EtOAcF)); and isolated compounds (curcuhydroquinone O-ß-glucose (CUR) and α and ß piptizol (Pip)) reduced the following inflammatory variables: neutrophils, protein concentrations of the exudate, MPO, ADA, NOx, and proinflammatory cytokine (TNF-α, IFN-γ, IL-6, and IL-12) levels in mouse pleural fluid leakage. The compounds CUR and Pip also decreased the p65 protein phosphorylation of NF-kappa B and p38 (MAPK) in lung tissue. J. sellowii L. has important anti-inflammatory activity with potential applications in drug development against inflammatory disorders. These effects found can be attributed to the ability of the new isolated compounds CUR and Pip to suppress p65 NF-κB and p-p38 MAPK pathways.

Systemic Administration of Calea pinnatifida Inhibits Inflammation Induced by Carrageenan in a Murine Model of Pulmonary Neutrophilia.

OBJECTIVE: The aim of this study was to investigate the anti-inflammatory effects of the crude extract (CE), derived fraction, and isolated compounds from Calea pinnatifida leaves in a mouse model of pulmonary neutrophilia. METHODS: The CE and derived fractions, hexane, ethyl acetate, and methanol, were obtained from C. pinnatifida leaves. The compounds 3,5- and 4,5-di-O-E-caffeoylquinic acids were isolated from the EtOAc fraction using chromatography and were identified using infrared spectroscopic data and nuclear magnetic resonance (1H and 13C NMR). Leukocytes count, protein concentration of the exudate, myeloperoxidase (MPO) and adenosine deaminase (ADA), and nitrate/nitrite (NO x ), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1ß), and interleukin-17A (IL-17A) levels were determined in the pleural fluid leakage after 4 h of pleurisy induction. We also analyzed the effects of isolated compounds on the phosphorylation of both p65 and p38 in the lung tissue. RESULTS: The CE, its fractions, and isolated compounds inhibited leukocyte activation, protein concentration of the exudate, and MPO, ADA, NO x , TNF-α, IL-1ß, and IL-17A levels. 3,5- and 4,5-di-O-E-caffeoylquinic acids also inhibited phosphorylation of both p65 and p38 (P < 0.05). CONCLUSION: This study demonstrated that C. pinnatifida presents important anti-inflammatory properties by inhibiting activated leukocytes and protein concentration of the exudate. These effects were related to the inhibition of proinflammatory mediators. The dicaffeoylquinic acids may be partially responsible for these anti-inflammatory properties through the inhibition of nuclear transcription factor kappa B and mitogen-activated protein kinase pathways.

Phenolic Compounds Isolated from Calea uniflora Less. Promote Anti-Inflammatory and Antioxidant Effects in Mice Neutrophils (Ex Vivo) and in Mice Pleurisy Model (In Vivo).

The literature shows that phenolic compounds possess important antioxidant and anti-inflammatory activities; however, the mechanism underlying these effects is not elucidated yet. The genus Calea is used in folk medicine to treat rheumatism, respiratory diseases, and digestive problems. In this context, some phenolic compounds were isolated with high purity from Calea uniflora Less. and identified as noreugenin (NRG) and α-hydroxy-butein (AH-BU). The aim of this study was to analyze the effect of these compounds on cell viability, the activity of myeloperoxidase (MPO), and apoptosis of mouse neutrophils using ex vivo tests. Furthermore, the effect of these compounds on the cytokines, interleukin 1 beta (IL-1ß), interleukin 17A (IL-17A), and interleukin 10 (IL-10), and oxidative stress was investigated by analyzing lipid peroxidation (the concentration of thiobarbituric acid reactive substances (TBARS)) and activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), using a murine model of neutrophilic inflammation. The NRG and AH-BU reduce MPO activity and increase neutrophil apoptosis (p < 0.05). These compounds reduced the generation of oxygen reactive species and IL-1ß and IL-17A levels but increased IL-10 levels (p < 0.05). This study demonstrated that NRG and AH-BU show a significant anti-inflammatory effect by inhibiting the MPO activity and increasing neutrophil apoptosis in primary cultures of mouse neutrophils. These effects were at least partially associated with blocking reactive species generation, inhibiting IL-1ß and IL-17A, and increasing IL-10 levels.

A single-step isolation by centrifugal partition chromatography of the potential anti-inflammatory glaucolide B from Lepidaploa chamissonis.

Sesquiterpene lactones (SL) are commonly found in Asteraceae and present a promising anti-inflammatory activity. Previously described in Lepidaploa genus, glaucolide B has never been investigated for its anti-inflammatory potential. This study aimed to establish an efficient process for the extraction of glaucolide B (1) from Lepidaploa chamissonis leaves and to develop a simple and fast method for its purification by using centrifugal partition chromatography (CPC), as well as to investigate in vitro the anti-inflammatory effects of glaucolide B. Thus, an optimized washing extractive process performed on L. chamissonis leaves allowed to obtain a SL enriched extract (4.11 g). After a successful defatting pretreatment of the crude extract, the glaucolide B enriched ethyl acetate portion (2.00 g) was fractionated by CPC affording, in a single-step isolation, compound 1 (1.04 g) in great yield (25%) and purity (97%). Cytotoxicity effect of 1 on RAW 264.7 macrophages was determined by using MTT assay, revealing a CC10 of 14.11 µM. Compound 1 at 1, 3 and 10 µM inhibited the nitrite/nitrate (NOx) metabolites production and the pro-inflammatory interleukin 6 (IL-6) secretion on lipopolysaccharide-stimulated RAW 264.7 cells. The extractive process used turned to be selective for SL and CPC technique proved a simple and effective tool for the isolation of 1 within few hours. Isolated for the first time from L. chamissonis leaves, glaucolide B presented a significant inhibitory effect on both NO and IL-6 secretion under non-toxic concentrations.

The anti-inflammatory effect of Ilex paraguariensis A. St. Hil (Mate) in a murine model of pleurisy.

Ilex paraguariensis is a native plant from Southern America, where it is used as a beverage. In traditional medicine, it is used to treat many diseases including inflammation. However, we do not yet know precisely how this effect occurs. We therefore evaluated its anti-inflammatory effect in a murine model of pleurisy. The standardized CE, BF and ARF fractions, Caf, Rut and CGA were able to reduce leukocyte migration, exudate concentration, MPO and ADA activities and NOx levels. Moreover, I. paraguariensis also inhibited the release of Th1/Th17 pro-inflammatory cytokines, while increasing IL-10 production and improving the histological architecture of inflamed lungs. In addition, its major compounds decreased p65 NF-κB phosphorylation. Based on our results, we can conclude that I. paraguariensis exerts its anti-inflammatory action by attenuating the Th1/Th17 polarization in this model. This fact suggests that the use of this plant as a beverage can protect against Th1/Th17 inflammatory diseases.

Modulatory effect of Senecio brasiliensis (Spreng) Less. in a murine model of inflammation induced by carrageenan into the pleural cavity.

ETHNOPHARMACOLOGICAL RELEVANCE: Senecio brasiliensis (Spreng) Less (S. brasiliensis), known as "Flor-das-almas", "Margaridinha" or "Maria mole", is used in folk medicine as an anti-inflammatory and to treat gastric ulcers and stomach pain. While the Senecio genus has been widely studied for its pharmacological activities to support its use in traditional medicine, few studies focus on the anti-inflammatory activities of the species. AIM OF THE STUDY: To investigate the anti-inflammatory activities of S. brasiliensis, a specie native to Brazil, using a murine model of pleurisy induced by carrageenan. MATERIAL AND METHODS: The flowers of S. brasiliensis were air-dried for 3 days and subjected to ethanol (96%) extraction for 7 days to obtain the crude extract (CE). The CE was subjected to acid-base extraction to obtain the alkaloid fraction (AF). The hexane (HEX), dichloromethane (DCM) and ethyl acetate (EtOAc) fractions were obtained by extracting from CE with different solvents. The alkaloids senecionine (Sen), integerrimine (Int) and senecionine N-oxide were obtained from AF by chromatographic fractionation and a mixture of 1,4-, 3,4-, 3,5- and 4,5-dicaffeoylquinic acids (DCQs) were obtained from the EtOAc fraction. The isolated alkaloids were identified through spectroscopic analysis of IR, NMR and LC-MS coupled with electrospray ionization mass spectrometry (ESI-MS), and the dicaffeoylquinic acids through the hierarchical key method. Swiss mice were used in the in vivo experiments. We evaluated the effect of the CE, its derived fractions (AF, HEX, DCM and EtOAc), and the isolated compounds (Sen, Int, N-oxide senecionine, and DCQs) on: leukocyte migration, exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, and tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 17A levels in the fluid leakage from the pleural cavity using a mouse model of pleurisy induced by carrageenan. The effects of the isolated compounds, Sen, Int, N-oxide senecionine and DCQs, were also analyzed for their ability to inhibit p65 phosphorylation (p-p65) in the nuclear factor-kappa B (NF-κB) pathway in the lung tissue. MPO and ADA were analyzed by colorimetric assays, and the cytokines and protein p65 levels were determined using an enzyme immunoassay (EIA). RESULTS: The CE, its EtOAc and AF fractions, and its isolated compounds (Sen, Int and DCQs), significantly reduced leukocyte migration (P < 0.05), MPO and ADA activities (P < 0.01), and TNF-α (P < 0.05), and IL-17A levels (P < 0.01). The CE, the EtOAc and AF fractions, and the DCQs also decreased IL-1ß levels (P < 0.01). The isolated compounds, Sen, Int and the DCQs, inhibited p65 phosphorylation (NF-κB) (P < 0.05). CONCLUSION: This study demonstrated that S. brasiliensis has important anti-inflammatory properties that are capable of inhibiting activated leukocytes by decreasing neutrophil migration. This effect may be attributed to the inhibition of pro-inflammatory cytokines and the reduction of the NF-κB pathway. The compounds Sen, Int, and DCQs may be responsible for the anti-inflammatory actions of S. brasiliensis.

Jungia sellowii suppresses the carrageenan-induced inflammatory response in the mouse model of pleurisy.

This study was conducted to explore the anti-inflammatory effect of Jungia sellowii (Asteraceae) using a murine model of pleurisy induced by carrageenan (Cg). This plant is used in southern Brazil to treat inflammatory diseases. J. sellowii leaves were extracted with ethanol/water to obtain the crude extract (CE), which was fractionated with different solvents, yielding n-hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and n-butanol (BuOH) fractions, and aqueous fraction (Aq). The major compounds succinic acid (SA) and lactic acid (LA) were isolated from Aq fraction, and their structures were determined by (1)H and (13)C NMR. Pleurisy was induced by Cg (Saleh et al. 1996). The leukocytes, exudation, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, metabolites of nitric oxide (NO x ) levels, protein levels and mRNA expression for interleukin 1 beta (IL-1ß), tumour necrosis factor alpha (TNF-α), interleukin 17A (IL17A) and inducible of nitric oxide synthase (iNOs), and p65 protein phosphorylation (NF-κB) were analysed 4 h after pleurisy induction. Animals pre-treated with CE, BuOH, Aq, SA, or LA inhibited leukocytes, exudation, MPO and ADA activities, NO x , IL-1ß, TNF-α, and IL-17A levels, and the mRNA expression for IL-1ß, TNF-α, IL-17A, iNOS, and p65 protein phosphorylation (NF-κB) (p < 0.05). Our study demonstrated that J. sellowii can protect against inflammation induced by Cg by decreasing the leukocytes and exudation. Its effects are related to the decrease of either proinflammatory cytokines and/or NO x . The isolated compounds SA and LA may play an important role in this anti-inflammatory action by inhibiting all the studied parameters. The anti-inflammatory properties of these compounds are due to the downregulation of NF-κB.

Systemic administration of Rosmarinus officinalis attenuates the inflammatory response induced by carrageenan in the mouse model of pleurisy.

Rosmarinus officinalis, also named rosemary, is a native plant from the Mediterranean region that is useful for the treatment of inflammatory diseases. Studies using experimental models and/or in vitro tests have shown the important biological effects of rosemary. In this context, the mechanism of the anti-inflammatory activity of rosemary must be investigated to support the discovery of new substances with anti-inflammatory effects. The aim of the present study was to investigate the anti-inflammatory effects of crude extract oil free obtained from the leaves of rosemary in an animal model of inflammation, thus evaluating its medicinal use for the treatment of inflammatory conditions. Also its ethanol, hexane, and ethyl acetate fractions, as well as its isolated compounds carnosol and rosmarinic acid were analyzed. Swiss mice were used for the in vivo experiments. The effect of this herb on the inhibition of the leukocytes, exudation, myeloperoxidase, and adenosine-deaminase activities, nitrite/nitrate, interleukin 17A, and interleukin 10 levels and mRNA expression was determined. The crude extract and its derived fractions, in addition to its isolated compounds, inhibited leukocytes and decreased exudation and myeloperoxidase and adenosine-deaminase activities, as well as nitrite/nitrate and interleukin 17A levels and mRNA expression, besides increasing interleukin 10 levels and mRNA expression. Rosemary showed important anti-inflammatory activity by inhibiting leukocytes and decreasing exudation. These effects were associated with a decrease in the proinflammatory parameters (myeloperoxidase, adenosine-deaminase, nitrite/nitrate, and interleukin 17A) and an increase in the anti-inflammatory cytokine (interleukin 10). This study confirms the anti-inflammatory properties of rosemary and validates its use in folk medicine to treat inflammatory diseases such as rheumatism and asthma.

The brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, and induced nitric oxide synthase expressions after low-level laser therapy in an axonotmesis experimental model.

BACKGROUND DATA: A robust body of evidence has shown that low-level laser therapy (LLLT) improves peripheral nerve regeneration. However, the biochemical background triggered in this process is not yet fully understood. OBJECTIVE: The purpose of this study was to evaluate the mRNA expression of neurotrophic factors (brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], and neurotrophin-3, [NT-3]) and also an inflammatory marker (induced nitric oxide synthase [iNOS]) in an axonotmesis experimental model after low-level laser therapy. METHODS: Thirty-six adult male Wistar rats (250-350 g) were subjected to right sciatic nerve crush injury, and 24 h later, the animals in the three different experimental groups (n=18) were irradiated on a daily basis with helium-neon laser (collimated HeNe laser, continuous emission, wavelength: 632.8 nm, power density: 0.5 mW/cm(2), irradiation time: 20 sec, energy density: 10 J/cm(2)) during 7, 14, and 21 consecutive days, respectively. The control group (n=18) underwent the same procedures, but with the equipment turned off. At the end of the experiments, animals were killed with an overdose of anesthesia to remove samples from the sciatic nerve lesion epicenter to determine the mRNA expression of BDNF, NGF, NT-3 and iNOS enzyme. RESULTS: Comparisons between groups showed that HeNe laser increased the mRNA expression of both BDNF and NGF factors after 14 days of LLLT, with peak expression at the 21st day. Increase in NT-3 mRNA expression was not observed. In addition, HeNe laser produced iNOS expression reduction, which played an important role in the inflammatory process. CONCLUSIONS: The reported data could have a relevant practical value because LLLT is a noninvasive procedure, and have revealed significant increase in neurotrophic factor expressions and inflammatory process reduction, opening the possibility of using LLLT as an important aid to nerve regeneration process.

Protected effect of Esenbeckia leiocarpa upon the inflammatory response induced by carrageenan in a murine air pouch model.

UNLABELLED: This study was conducted to investigate the anti-inflammatory efficacy of Esenbeckia leiocarpa against the inflammation caused by the carrageenan using a murine air pouch model. MATERIAL AND METHODS: The effects of the crude hydroalcoholic extract (CHE), fractions (n-hexane (Hex) and ethyl acetate (AcOEt)), subfractions (polar (Pol) and nonpolar (Nonpol)), or isolated compounds (dihydrocorynantheol (DHC) and beta-sitosterol (ß-Sit)) isolated from CHE upon leukocytes, exudate, myeloperoxidase (MPO) adenosine-deaminase (ADA), nitrate/nitrite (NO(x)), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and inhibitory kappa-B-alpha (IκB-α) degradation were evaluated. The CHE, Alk, Pol, Nonpol, DHC and ß-Sit, inhibited leukocytes, exudate, MPO and ADA, NO(x), IL-1ß, and TNF-α (P<0.05). The Hex and AcOEt fractions inhibited all of the proinflammatory parameters, except the exudate. The compound DHC prevented the IκB-α degradation. CONCLUSION: E. leiocarpa possesses important anti-inflammatory properties. These inhibitory effects occurred along with the downregulation of nitric oxide, IL-1ß and TNF-α levels. The isolated compounds DHC and ß-Sit may be partially responsible for these anti-inflammatory effects.

Antioxidant therapy attenuates oxidative insult caused by benzonidazole in chronic Chagas' heart disease.

Chronic chagasic cardiac patients are exposed to oxidative stress that apparently contributes to disease progression. Benznidazole (BZN) is the main drug used for the treatment of chagasic patients and its action involves the generation of reactive species. 41 patients with Chagas' heart disease were selected and biomarkers of oxidative stress were measured before and after 2 months of BZN treatment (5 mg/kg/day) and the subsequent antioxidant supplementation with vitamin E (800 UI/day) and C (500 mg/day) during 6 months. Patients were classified according to the modified Los Andes clinical hemodynamic classification in groups IA, IB, II and III, and the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR), as well as the contents of reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), protein carbonyl (PC), vitamin E and C and nitric oxide (NO), myeloperoxidase (MPO) and adenosine deaminase (ADA) activities were measured in their blood. Excepting in group III, after BZN treatment SOD, CAT, GPx and GST activities as well as PC levels were enhanced while vitamin E levels were decreased in these groups. After antioxidant supplementation the activities of SOD, GPx and GR were decreased whereas PC, TBARS, NO, and GSH levels were decreased. In conclusion, BZN treatment promoted an oxidative insult in such patients while the antioxidant supplementation was able to attenuate this effect by increasing vitamin E levels, decreasing PC and TBARS levels, inhibiting SOD, GPx and GR activities as well as inflammatory markers, mainly in stages with less cardiac involvement.

Topical anti-inflammatory activity of Serjania erecta Radlk (Sapindaceae) extracts.

Serjania erecta Radlk (Sapindaceae), commonly called cinco-folhas or cipó-cinco-folhas in Brazil, is thought to be effective for treating several inflammatory diseases. In order to verify the topical anti-inflammatory effect of Serjania erecta, hydroalcoholic extract and fractions were obtained by extraction in solvents of increasing polarity and were tested in mouse models using croton-oil-induced inflammation. Our findings showed that topical application of Serjania erecta hydroalcoholic extract (0.01-3.0 mg/ear), and the dichloromethane (0.03-1.0 mg/ear), ethyl acetate (0.03-1.0 mg/ear), and hexane (0.003-1.0 mg/ear) fractions revealed significant activity, causing a dose-dependent reduction of croton-oil ear edema (ID(50)=0.14 mg/ear, 0.23 mg/ear, 0.14 mg/ear, 0.04 mg/ear, respectively). The extract and all tested fractions also decreased tissue myeloperoxidase activity (indicative of polymorphonuclear leukocytes influx) in mouse-ears treated with croton oil with a maximum inhibition of 72% at 3.0 mg/ear for the hydroalcoholic extract and 81%, 78%, and 83% at 1.0mg/ear for dichloromethane, ethyl acetate and hexane fractions, respectively. As expected, dexamethasone (0.05 mg/ear) was effective in inhibiting both edema and myeloperoxidase activity (99% and 82%, respectively). In conclusion, our results indicate a topical anti-inflammatory effect for the species of Serjania studied.