Unravelling the Gastroprotective Potential of Kefir: Exploring Antioxidant Effects in Preventing Gastric Ulcers.

The present study was conducted to evaluate the protective effect of milk kefir against NSAID-induced gastric ulcers. Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg/kg), and 4% milk kefir (Kefir; 0.3 mL/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-α levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1-35 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-α systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.

Infrared laser therapy decreases systemic oxidative stress and inflammation in hypercholesterolemic mice with periodontitis.

BACKGROUND: Near-infrared irradiation photobiomodulation (NIR-PBM) has been successfully used in periodontal treatment as an adjuvant tool to locally improve cell function and regeneration. Although the relationship between periodontitis and systemic disease constitutes an important aspect of periodontal clinical research, the systemic effects of NIR-PBM in periodontitis are not well known. In this study, we aimed to investigate the effects of NIR-PBM on systemic oxidative stress and inflammation in an apolipoprotein E (ApoE) knockout mouse model of periodontal disease (PD). METHODS: We evaluated alveolar bone loss by measuring the distance from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC), reactive oxygen species (ROS) production in blood cells, inflammatory activity, plasma cholesterol levels, and lipid peroxidation levels in three experimental groups: (1) ApoEC, control group without intervention; (2) ApoEP, first molar ligation-induced periodontitis for 4 weeks; and (3) ApoEP + PBM, exposed to 808 nm continuous wave, ø ~ 3 mm2, 100 mW, 60 s of NIR-PBM for 7 consecutive days after 4 weeks of periodontitis. At the end of the experimental protocols, ApoEP mice presented significantly increased alveolar bone loss, ROS production, inflammatory activity, plasma cholesterol, and lipid peroxidation levels compared to the ApoEC group (P < 0.05). NIR-PBM for 7 days in the ApoEP + PBM mice significantly decreased systemic ROS production, inflammatory response, plasma cholesterol, and lipid peroxidation levels, similar to those found in the ApoEC group (P > 0.05). However, it was not capable of preventing alveolar bone loss (P > 0.05 compared to ApoEP mice). CONCLUSION: A 7-day treatment with NIR-PBM effectively reduces systemic oxidative stress and inflammatory parameters in hypercholesterolemic mice with PD. However, more studies with longer evaluation times are needed to confirm the systemic effects of locally applied NIR-PBM on PD associated with hypercholesterolemia.

Efeitos clínicos da fotobiomodulação como terapia adjuvante não-cirúrgica na periodontite crônica: uma revisão integrativa da literatura / Clinical effects of photobiomodulation as non-surgical adjuvant therapy for chronic periodontitis: an integrative literature review

Introdução: A doença periodontal, de origem infecciosa, constitui diferentes quadros clínicos de caráter multifatorial e inflamatório. A fotobiomodulação é uma técnica não invasiva que tem demonstrado ser capaz de diminuir a inflamação e proporcionar alívio da dor. Estudos também demonstraram que a adoção da fotobiomodulação adjuvante à raspagem e alisamento radicular tem sido capaz de reduzir a carga bacteriana proveniente da periodontite crônica. Objetivos: Analisar os efeitos da fotobiomodulação como terapia adjuvante à raspagem e ao alisamento radicular no tratamento da periodontite crônica publicados nos últimos cinco anos. Métodos: Trata-se de uma revisão integrativa da literatura, realizada no período de setembro a novembro de 2021, mediante a utilização dos seguintes descritores: "Periodontitis", "Photobiomodulation" e "Therapy, selecionando artigos publicados em inglês durante o período entre 2016 a 2021. Resultados: Foram identificados 47 trabalhos. Destes, foram excluídos 39 estudos que se dispersaram do tema e 2 que se encontravam indisponíveis para o acesso, resultando em 6 artigos que foram consultados integralmente. Foi consenso entre os artigos consultados que a prática da fotobiomodulação tornou-se um potencial agente terapêutico no tratamento da periodontite crônica contribuindo para a redução da contagem de periodontopatógenos e que atua de maneira coadjuvante às raspagens radiculares. Conclusão: A fotobiomodulação mostrou-se uma ferramenta promissora na área odontológica. Entretanto, a grande variedade nos parâmetros de tratamentos e protocolos utilizados na fotobiomodulação impossibilita uma comparação e uma análise mais crítica e rigorosa dos resultados obtidos nos trabalhos analisados.

Introduction: Periodontal disease, which has an infectious origin, constitutes a multifactorial and inflammatory different clinical condition of multifactorial, inflammatory, and infectious origin. Photobiomodulation is a non-invasive technique that has been shown to decrease inflammation and provide pain relief. Studies also have shown that the choosing of photobiomodulation as adjuvant therapy to scaling and root planing has been able to reduce the bacterial load from chronic periodontitis. Objectives: To analyze the effects of photobiomodulation as an adjuvant therapy to scaling and root planing in the treatment of chronic periodontitis in the studies published in the last five years. Methods: This is an integrative literature review, carried out from September to November 2021, using the following descriptors: "Periodontitis", "Photobiomodulation" and "Therapy, from selected articles published in English during the period between 2016 to 2021. Results: From the research and selection of studies to compose this integrative literature review, 47 studies were initially identified based on the descriptors. From those, 39 papers that were outside from the topic and 2 papers that were unavailable for access were excluded from the present review. Then remained, 6 articles that were fully consulted. The practice of photobiomodulation has become a potential therapeutic agent in the treatment of chronic periodontitis reducing the count of periodontopathogens and as an adjunct therapy to root scaling. Conclusion: Photobiomodulation therapy has become a promising tool in the dental field, however, the great variety in the treatment parameters and protocols used for photobiomodulation makes impossible to compare and perform a more critical and rigorous analysis of the results collected in the present work.

Use of kefir peptide (Kef-1) as an emerging approach for the treatment of oxidative stress and inflammation in 2K1C mice.

The benefits of kefir consumption are partially due to the rich composition of bioactive molecules released from its fermentation. Angiotensin-converting enzyme (ACE) inhibitors are bioactive molecules with potential use in the treatment or prevention of hypertension, heart failure, and myocardial infarction. Here, the in vivo actions of the Kef-1 peptide, an ACE inhibitor derived from kefir, were evaluated in an angiotensin II-dependent hypertension model. The Kef-1 peptide showed a potential anti-hypertensive effect. Additionally, Kef-1 exhibited systemic antioxidant and anti-inflammatory activities. In smooth muscle cells (SMCs), the Kef-1 peptide decreased ROS production through the reduced participation of NADPH oxidase and mitochondria. The aorta of 2K1C mice treated with Kef-1 showed lesser wall-thickening and partial restoration of the endothelial structure. In conclusion, these novel findings highlight the in vivo biological potential of this peptide demonstrating that Kef-1 may be a relevant nutraceutical treatment for cardiovascular diseases.

Toxicological effects of air settled particles from the Vitoria Metropolitan Area mediated by oxidative stress, pro-inflammatory mediators and NFΚB pathway.

Atmospheric pollution is a major environmental and public health risk due to its effect on global air quality and climate. Increase in pollutants concentrations, especially particulate matter (PM), are associated with increased respiratory diseases. The pathophysiology of respiratory diseases involves molecular and cellular mechanisms as inflammatory biomarkers and reactive oxygen species production. Thus, the present study aimed to investigate the in vitro cytotoxic and pro-inflammatory effects of particulate matter (PM) of six monitoring stations (1-6) from the Vitoria Metropolitan Area (VMA), Espirito Santo, Brazil in 2018. The PM was chemically characterized by inductively coupled plasma mass spectrometry. In vitro cytotoxic effects of PM (3.12-200.0 µg/mL) were analyzed in human lung epithelial cells (A549) and macrophage cells (RAW 264.7) by MTT assay (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide). To investigate the pro-inflammatory effects of PM in RAW 264.7 cells, the levels of proinflammatory mediators such as nitric oxide (NO), superoxide anion (O2•-), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and the activation of nuclear factor kappa B (NF- κB) were measured. The comet assay evaluated genotoxicity. Cell cycle, oxidative stress (DCF and DHE), and apoptosis were analyzed by flow cytometry. Chemical analysis of PM revealed aluminum (Al) and Iron (Fe) as the major chemical elements in all studied monitoring stations. In addition, worrying concentrations of mercury (Hg) were detected in the PM. The in vitro results showed that PM presents a dose-dependent cytotoxic effect in macrophage and pulmonary epithelial cell lines. The PM increased the production of NO, O2•-, and pro-inflammatory cytokines TNF-α and IL-6. PM also promoted alterations in the cell cycle, increased apoptosis frequency, and DNA damage. Moreover, PM increased the expression NF-κB. In addition, a positive correlation between Al and Fe and ROS production was observed. Based on the results obtained during the study period, it was concluded that the sedimented particles from the VMA might have deleterious effects on human health, which was evidenced by the increase in oxidative stress, an increase in pro-inflammatory mediators, and genotoxic effects partially mediated by the NF-κB pathway. These results add aspects to elucidate the molecular mechanisms involved in the effects of sedimented particles in vivo and in vitro.

The influence of splenic tissue on the survival and TCD4 and TCD8 lymphocyte rates in rats subjected to fecal peritonitis induction.

PURPOSE: Comparing survival rates of rats subjected to spleen procedures after fecal peritonitis induction. Assessing changes in TCD4 and CD8 lymphocyte rates before and after the procedures. Correlating animal survival with CD4 and CD8 lymphocytes. METHODS: Thirty male Wistar rats were distributed into 3 groups of ten: spleen manipulation (SM); total splenectomy (TS); subtotal splenectomy with preservation of the inferior pole (IP). Rats were subjected to surgical procedure depending on the group. Seven days after surgery they underwent induction of peritonitis and survival time was recorded. All animals were subjected to two blood collections: before surgery and 70 days after it for TCD4/TCD8 lymphocyte counting. RESULTS: Mean survival time was longer in the IP and SM groups and shorter in the TS group; there was significant difference between them. The comparison of the median number of CD4 did not present changes, whereas the comparison of the median number of CD8 decreased in the SM and IP groups. The correlation between the median number of TCD4 and TCD8 lymphocytes and the animals' survival was not significant. CONCLUSION: The maintenance of splenic tissue contributed to increase the survival of rats and there was a change in the number of TCD8 lymphocytes.

Oxidative Stress and Dementia in Alzheimer's Patients: Effects of Synbiotic Supplementation.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in elderly patients. Recently, several studies have shown that inflammation and oxidative stress precede the cardinal neuropathological manifestations of AD. In view of the proven antioxidant effects of probiotics, we proposed that continuous dietary supplementation with milk fermented with kefir grains might improve cognitive and metabolic and/or cellular disorders in the AD patients. METHODS: This study was designed as an uncontrolled clinical investigation to test the effects of probiotic-fermented milk supplementation (2 mL/kg/daily) for 90 days in AD patients exhibiting cognitive deficit. Cognitive assessment, cytokine expression, systemic oxidative stress levels, and blood cell damage biomarkers were evaluated before (T0) and after (T90) kefir synbiotic supplementation. RESULTS: When the patients were challenged to solve 8 classical tests, the majority exhibit a marked improvement in memory, visual-spatial/abstraction abilities, and executive/language functions. At the end of the treatment, the cytometric analysis showed an absolute/relative decrease in several cytokine markers of inflammation and oxidative stress markers (·O2 -, H2O2, and ONOO-, ~30%) accompanied by an increase in NO bioavailability (100%). In agreement with the above findings by using the same technique, we observed in a similar magnitude an improvement of serum protein oxidation, mitochondrial dysfunction, DNA damage/repair, and apoptosis. CONCLUSION: In conclusion, we demonstrated that kefir improves cognitive deficits, which seems to be linked with three important factors of the AD-systemic inflammation, oxidative stress, and blood cell damage-and may be a promising adjuvant therapy against the AD progression.

Sildenafil reduces aortic endothelial dysfunction and structural damage in spontaneously hypertensive rats: Role of NO, NADPH and COX-1 pathways.

Arterial hypertension is a condition associated with endothelial dysfunction, accompanied by an imbalance in the production of reactive oxygen species (ROS) and NO. The aim of this study was to investigate and elucidate the possible mechanisms of sildenafil, a selective phosphodiesterase-5 inhibitor, actions on endothelial function in aortas from spontaneously hypertensive rats (SHR). SHR treated with sildenafil (40 mg/kg/day, p.o., 3 weeks) were compared to untreated SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and vascular reactivity was determined in isolated rat aortic rings. Circulating endothelial progenitor cells and systemic ROS were measured by flow cytometry. Plasmatic total antioxidant capacity, NO production and aorta lipid peroxidation were determined by spectrophotometry. Scanning electron microscopy was used for structural analysis of the endothelial surface. Sildenafil reduced high SBP and partially restored the vasodilator response to acetylcholine and sodium nitroprusside in SHR aortic rings. Using selective inhibitors, our experiments revealed an augmented participation of NO, with a simultaneous decrease of oxidative stress and of cyclooxygenase-1 (COX-1)-derived prostanoids contribution in the endothelium-dependent vasodilation in sildenafil-treated SHR compared to non-treated SHR. Also, the relaxant responses to sildenafil and 8-Br-cGMP were normalized in sildenafil-treated SHR and sildenafil restored the pro-oxidant/antioxidant balance and the endothelial architecture. In conclusion, sildenafil reverses endothelial dysfunction in SHR by improving vascular relaxation to acetylcholine with increased NO bioavailability, reducing the oxidative stress and COX-1 prostanoids, and improving cGMP/PKG signaling. Also, sildenafil reduces structural endothelial damage. Thus, sildenafil is a promising novel pharmacologic strategy to treat endothelial dysfunction in hypertensive states reinforcing its potential role as adjuvant in the pharmacotherapy of cardiovascular diseases.

The influence of splenic tissue on the survival and TCD4 and TCD8 lymphocyte rates in rats subjected to fecal peritonitis induction

Abstract Purpose: Comparing survival rates of rats subjected to spleen procedures after fecal peritonitis induction. Assessing changes in TCD4 and CD8 lymphocyte rates before and after the procedures. Correlating animal survival with CD4 and CD8 lymphocytes. Methods: Thirty male Wistar rats were distributed into 3 groups of ten: spleen manipulation (SM); total splenectomy (TS); subtotal splenectomy with preservation of the inferior pole (IP). Rats were subjected to surgical procedure depending on the group. Seven days after surgery they underwent induction of peritonitis and survival time was recorded. All animals were subjected to two blood collections: before surgery and 70 days after it for TCD4/TCD8 lymphocyte counting. Results: Mean survival time was longer in the IP and SM groups and shorter in the TS group; there was significant difference between them. The comparison of the median number of CD4 did not present changes, whereas the comparison of the median number of CD8 decreased in the SM and IP groups. The correlation between the median number of TCD4 and TCD8 lymphocytes and the animals' survival was not significant. Conclusion: The maintenance of splenic tissue contributed to increase the survival of rats and there was a change in the number of TCD8 lymphocytes.

Worsening of Oxidative Stress, DNA Damage, and Atherosclerotic Lesions in Aged LDLr-/- Mice after Consumption of Guarana Soft Drinks.

BACKGROUND: Excessive consumption of soft drinks (SD) has become a health problem worldwide due to its association with related cardiovascular diseases. We investigated the possible impacts associated with the consumption of Brazilian guarana (normal and zero) SD in dyslipidemic mice, thus mitigating potential clinical confounders such as poor-quality diet, lifestyle, body composition, and/or comorbidities. METHODS: Sixteen-month-old LDLr-/- mice were divided into the following groups: (1) control; (2) GSD: normal guarana SD; and (3) Z-GSD: zero guarana SD. All were fed ad libitum, and blood pressure was measured noninvasively. After 8 weeks, aorta, blood, liver, and stomach samples were collected for histological and biochemical analyses. RESULTS: Guarana soft drinks increased atherosclerosis (~60%) and were associated with hypercholesterolemia, hypertension, oxidative stress, DNA fragmentation, and apoptosis (~2-fold) of blood cells, besides presenting an increase in liver and gastric damage even in normoglycemia. Interestingly, Z-GSD did not cause the aforementioned changes, except in hemodynamic and renal parameters. CONCLUSIONS: Chronic administration of GSD is prooxidative, compromising the cardiovascular, gastric, and hepatic systems; the effects are due at least in part to free sugar consumption but not to guarana extract per se.

Silymarin protects against radiocontrast-induced nephropathy in mice.

Silymarin, an extract from Silybum marianum (milk thistle) containing a standardized mixture of flavonolignans that ameliorates some types of liver disease and, more recently, kidney damage, could be used for the ROS-scavenging effect of these antioxidants. Furthermore, contrast-induced nephropathy (CIN) is an iatrogenic impairment of renal function in patients subjected to angiographic procedures for which there is not yet a successful preventative treatment. Recent evidence has shown that this event is related to tubular/vascular injury activated mainly by oxidative stress. However, whether this bioavailable and pharmacologically safe extract protects against CIN is not clear. We proposed to evaluate the possible protective role of the antioxidant silymarin in an experimental model of CIN. Adult male Swiss mice were separated into 6 groups and pretreated orally with silymarin (50, 200 and 300 mg/kg), N-acetylcysteine (200 mg/kg) or vehicle for 5 days before the CIN and control groups. Renal function was analyzed by plasma creatinine, urea and cystatin C levels. Additionally, blood reactive oxygen species (ROS) were evaluated using ROS bioavailability, protein oxidation and DNA damage. Renal oxidative damage was evaluated using apoptosis/cell viability assays and histological analysis. We showed that silymarin preserved renal function and decreased systemic and renal oxidative damage (antigenotoxic and antiapoptotic properties, respectively) in a dose-dependent manner and was superior to conventional treatment with N-acetylcysteine. Histologically, silymarin treatment also had beneficial effects on renal glomerular and tubular injuries. Therefore, silymarin prophylaxis may be an interesting strategy for the prevention of CIN.

Avocado seeds (Persea americana Mill.) prevents indomethacin-induced gastric ulcer in mice.

The long-term use of anti-inflammatory drugs is the most common cause of gastric ulcer disease, one of the major gastrointestinal disorders affecting people worldwide. Persea americana Mill. (avocado) seed is a by-product generally discarded as waste, but can be used to treat gastric disorder due to its anti-inflammatory, antioxidant and antimicrobial activities. The aim of the present study was to evaluate the potential protective effects of the ethyl acetate fraction of avocado seeds (SEAP) extracts against indomethacin-induced gastric ulcer in mice. It was found that SEAP were effective in mitigating oxidative stress through a decrease on the oxidized products levels (reduction of 90% in lipid peroxidation in plasma) and increasing superoxide dismutase enzyme (SOD) activity (4.25-fold increase compared to the indomethacin group), also preventing the rise in ulcer and lesions areas (92% of protection) and histological changes induced by indomethacin. Chemical analysis using mass spectrometry by (-)-ESI-FT-ICR MS revealed the presence of (-)-epicatechin and (+)-catechin, confirmed by HPLC-DAD, and other important phenolic compounds in avocado seeds, such as caffeoylquinic acid, flavonoids, phenylpropanoids and tannins, substances that promote inhibition of pathways involved in gastric ulcer formation. Thus, avocado seeds extract may be a suitable natural source for the prevention and treatment of gastric ulcer.

Identification of new bioactive peptides from Kefir milk through proteopeptidomics: Bioprospection of antihypertensive molecules.

Kefir, a probiotic beverage prepared from fermented milk, has been associated with antihypertensive activity. However, the bioactive molecules responsible for this activity still remain unclear. Therefore, in this study we aim to evaluate the mechanisms of the antihypertensive effects of Kefir in the two-kidney one-clip hypertension model, and to bioprospect for bioactive peptides identified by proteomic methodologies. Treatment with Kefir was performed via gavage, and resulted in a 37 mmHg reduction in systolic arterial pressure and 19% inhibition of angiotensin converting enzyme (ACE) activity. For the proteopeptidomic study, the protein extract of Kefir beverage and non-fermented bovine milk were analysed by MALDI-TOF mass spectrometry, and their tryptic digestion products sequenced via Shotgun proteomics (Q-Exactive mass spectrometer). A list of 35 peptides with potential hypertensive activity due to ACE inhibition were identified. These results demonstrate the benefits of Kefir products, and may guide the design of new antihypertensive drugs.

Gastroprotective effect of oral kefir on indomethacin-induced acute gastric lesions in mice: Impact on oxidative stress.

AIMS: This study investigated the gastroprotective effects and the systemic oxidative status of oral kefir pretreatment in albino mice submitted to acute gastric ulcer induced by indomethacin. MAIN METHODS: Male Swiss mice were divided into three groups (n = 7): Vehicle (0.3 mL of whole milk/100 g body weight, pH adjusted to 5.0), Kefir (0.3 mL of kefir/100 g body weight) and Proton Pump Inhibitor (PPI, 30 mg/kg of lansoprazole), via gavage for 14 days. Animals were fasted for 16 h and treated orally with indomethacin (40 mg/kg). After 6 h the animals were euthanized, the blood samples were obtained and used for the determination of ROS production, oxidation of macromolecules and apoptosis. The stomachs were removed, opened by the greater curvature, and a macroscopic analysis of the gastric lesions was performed. KEY FINDINGS: Our findings demonstrated that the symbiotic kefir significantly alleviated blood oxidative stress by reducing superoxide anion, hydrogen peroxide and hydroxyl/peroxynitrite radicals, thereby leading to reduced oxidative damage to macromolecules due to a decreased oxidative stress status in induced gastric lesions. These anti-oxidative properties might contribute favorably to the ulcer attenuation in the kefir group. SIGNIFICANCE: Taken together, these findings support a significant role played by the antioxidant actions of kefir in counteracting the gastric damage induced by this cyclooxygenase inhibitor. It is also worthy to mention that, kefir also exerted the gastroprotective property partly by inhibiting oxidative systemic damage. Based on these considerations, it was implied that kefir might be a contributor for the ROS-scavenging effect.

Genotoxic effect of Lippia alba (Mill.) N. E. Brown essential oil on fish (Oreochromis niloticus) and mammal (Mus musculus).

"Erva cidreira" (Lippia alba (Mill.) N. E. Brown) is popular for its therapeutic properties, especially its sedative properties. Such properties led to the discovery of the anesthetic action of Lippia alba essential oil in fish culture. The objective of this study was to evaluate the genotoxic effect of Lippia alba essential oil in fish and mammals. The oil was extracted by hydrodistillation with a Clevenger apparatus and analyzed by gas chromatography coupled to mass spectrometry (GC-MS), where the compounds linalool, eucalyptol, γ-muurolene, and caryophyllene were identified as the most abundant compounds. Lippia alba essential oil showed inhibitory activity on LPS-stimulated Nitric Oxide (NO) production (77% at 20 µg mL-1) in RAW 264.7 macrophages without influence cellular viability. Genotoxic action was observed by micronucleus and comet assay in the doses 100, 200 and 300 mg Kg-1, showing greater damage to fish than mammals. When we compared the treatment modes, greater damage was observed in the treatment by inhalation, but this was still not toxic. The oxidative stress measured by quantification of advanced oxidation protein products revealed low oxidation but significantly more harm than the control. These findings support the use of Lippia alba essential oil as an anesthetic for fish without harm to consumers.

In vitro cytotoxic activity of five commercial samples of Tribulus terrestris Linn in Espírito Santo (Brazil)

ABSTRACT The objective was to investigate the total saponin and protodioscin concentrations and the cytotoxicity in vitro, of five samples of the plant Tribulus terrestris, commercially available in the metropolitan region of Vitória - Espirito Santo, Brazil, and to compare them with the aqueous extract of the plant. The chromatographic profile and quantification of protodioscin in commercial samples and plant extract were evaluated by LC-MS/MS. The percentage of total saponins were determined by the colorimetric method. Extracts and protodioscin cytotoxicity were analyzed by the MTT assay in three cell lineages: fibroblasts (L929), ovarian cancer (Ovcar3) and murine hepatoma (Hepa1c1c7). All extracts displayed high levels of total saponins (207.2 to 780.3 mg g-1 of dry extract). The chromatographic profile revealed a wide diversity of compounds, and the saponin protodioscin was detected in only two extracts. One extract displayed high cytotoxicity, with IC50 values of 157.0, 38.2 and 7.4 µg mL-1 for the Ovcar3, Hepa1c1c7 and L929 cell lines, respectively. The other extracts displayed cytotoxic effects only at concentrations equal to or greater than 125.0 µg mL-1. Surprisingly, the most cytotoxic extract displayed the highest protodioscin concentration. Therefore, it is suggested that these products be marketed with caution, and followed-up by a certified healthcare professional.

Coadjuvants in the Diabetic Complications: Nutraceuticals and Drugs with Pleiotropic Effects.

Because diabetes mellitus (DM) is a multifactorial metabolic disease, its prevention and treatment has been a constant challenge for basic and clinical investigators focused on translating their discoveries into clinical treatment of this complex disorder. In this review, we highlight recent experimental and clinical evidences of potential coadjuvants in the management of DM, such as polyphenols (quercetin, resveratrol and silymarin), cultured probiotic microorganisms and drugs acting through direct/indirect or pleiotropic effects on glycemic control in DM. Among several options, we highlight new promising therapeutic coadjuvants, including chemical scavengers, the probiotic kefir and the phosphodiesterase 5 inhibitors, which besides the reduction of hyperglycemia and ameliorate insulin resistance, they reduce oxidative stress and improve endothelial dysfunction in the systemic vascular circulation. In the near future, experimental studies are expected to clear the intracellular pathways involving coadjuvants. The design of clinical trials may also contribute to new strategies with coadjuvants against the harmful effects of diabetic complications.

Association of interleukin-6 gene polymorphism with angina pectoris.

In this study, we investigated the role of the -174G>C polymorphism of interleukin-6 (IL-6) as a predisposing factor to angina pectoris. Patients were separated into 2 groups: angina (N = 72) and nonangina (N = 71). There were no statistical differences between groups for all cardiovascular risk factors evaluated. The GG genotype frequency was 18% lower in the angina than in the non-angina group, whereas GC + CC was 18% higher in the angina group (P = .036). The frequency of G allele was 11% lower in the angina than in the nonangina group and C allele was 11% higher in the angina group (P = .043). Patients carrying the C allele showed a 2-fold increased risk for angina pectoris (P = .036). Our study demonstrates a high incidence of the -174G>C polymorphism of the IL-6 gene in patients with angina pectoris compared with those carrying the G allele, reinforcing the contribution of genetic factors to the symptoms of angina pectoris.