Search

Resumen La terapia basada en incretinas lleva al control glucemico de una manera dependiente de glucosa con un bajo riesgo de hipoglucemia, por lo que resulta atractiva para su uso hospitalario. El objetivo de esta revision sistematica fue evaluar los beneficios de la terapia basada en incretinas en pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos. Se buscaron estudios publicados hasta agosto de 2021 en las bases de datos PubMed y Scopus. Se seleccionaron los ensayos clinicos que comparaban la terapia basada en incretinas (sola o en combinacion con insulina) versus el regimen con insulina. Los resultados de los estudios incluidos mostraron que la terapia basada en incretinas registro un promedio de glucosa sanguinea, un porcentaje de registros dentro de meta terapeutica y un porcentaje de falla al tratamiento similar al manejo con insulina, particularmente en pacientes con hiperglucemia leve a moderada. Ademas, el tratamiento basado en incretinas se asocio con una menor dosis total de insulina y una menor incidencia de hipoglucemia. En conclusion, la terapia basada en incretinas logro un control glucemico similar al tratamiento con insulina en los pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos, con la ventaja de disminuir el requerimiento insulinico y con menor riesgo de hipoglucemia.

The present study was made to determine the mouse in vivo micronuclei induction capacity of the venom obtained from three Mexican endemic snakes: Ophryacus undulatus, Ophryacus smaragdinus, and Oph...

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has affected millions of people globally. It was declared a pandemic by the World Health Organization in March 2020. The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a "cytokine storm" and the high oxidative stress responsible for the associated symptomatology. Not only respiratory symptoms are reported, but gastrointestinal symptoms (diarrhea, vomiting, and nausea) and liver abnormalities (high levels of aspartate aminotransferase, alanine aminotransferase transaminases, and bilirubin) are observed in at least 30% of patients. Reduced food intake and a delay in medical services may lead to malnutrition, which increases mortality and poor outcomes. This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury, taking energy and nutrient requirements and their impact on the immune response into account. The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.

Diabetes mellitus is a disease that is characterized by the chronic presence of blood glucose levels caused by a defect in the secretion of insulin or in the action of this hormone in the body which must be treated integrally with a multidisciplinary approach. The natural treatment of this disease is a common practice around the world, especially in Latin America, there are several clinical studies, in vivo or in vitro assays that focus on assessing the hypoglycemic capacity of various natural products used empirically by the population for years for the phytotherapeutic treatment of the disease as well as the chemicals related to the mechanism of action that produces the hypoglycaemic effect. In the present article, a brief review of the evidence of the hypoglycemic capacity of some natural products for the alternative treatment of diabetes mellitus 2

Cells have the ability to adapt to stressful environments as a part of their evolution. Physical exercise induces an increase of a demand for energy that must be met by mitochondria as the main (ATP) provider. However, this process leads to the increase of free radicals and the so-called reactive oxygen species (ROS), which are necessary for the maintenance of cell signaling and homeostasis. In addition, mitochondrial biogenesis is influenced by exercise in continuous crosstalk between the mitochondria and the nuclear genome. Excessive workloads may induce severe mitochondrial stress, resulting in oxidative damage. In this regard, the objective of this work was to provide a general overview of the molecular mechanisms involved in mitochondrial adaptation during exercise and to understand if some nutrients such as antioxidants may be implicated in blunt adaptation and/or an impact on the performance of exercise by different means.

Glucomannan is a highly branched polysaccharide with glycosidic linkages, constituted of mannoses and glucoses. In recent years, its usefulness due to its immunological, antioxidant and ant...

Studies have well documented that mutations in the adenomatous polyposis coli gene (APC) are involved in the development of different types of cancer. Therefore, the objective of the present report was to design and construct a sensitive nanostructured genosensor able to detect specific sequences of the APC gene in order to be applied in early carcinogenesis diagnosis. We used screen-printed gold electrodes (SPGE) modified with DNA probes and mercaptoundecanoic acid chemically immobilized on a gold sensor surface. APC complementary DNA sequences were hybridized on the previously immobilized DNA probes. Besides, we tested effects of different intercalating agents, and various temperatures on the hybridization reaction to increase the sensitivity and selectivity of our device. The evaluation of these processes was carried out by means of the cyclic voltammetry technique (CV) to monitor the redox reaction of [Fe(CN)6]3−/4− on the SPGE-s. The constructed genosensor exhibited an excellent response to identify the APC gene in a concentration range from 100 pM to 100 μM, with 43.92 pM as the limit of detection in the presence of doxorubicin as DNA intercalating agent. The selectivity of the device was tested by using a DNA sequence different from the APC gene, which shows negative response. Considering the importance of APC mutations in the development of tumors in the digestive, urogenital, and mammary tissues, here developed electrochemical genosensor, due to its easy management, short time of response, and high performance, may be useful for early cancer detection.

Ovalbumin is considered a protein of high nutritional value because it contains essential amino acids and is highly digestible. Therefore, it has a high biological value. Currently, the high food demand requires worldwide attention because food production is insufficient. Therefore, other alternatives are necessary to satisfy food demands, such as protein engineering. In this work, a protein with a high essential amino acid content similar to ovalbumin was synthesized by protein engineering, expressed, and digested in vitro. The assembly and sequential overlap extension PCR strategy was used to synthesize a 345-bp gene that encodes a high essential amino acid content protein (HEAAP). The 345-bp product was cloned into the vector pBAD TOPO®, and expressed in Escherichia coli BL21. PCR reactions and sequencing demonstrated the presence, orientation, and correct sequence of the insert. HEAAP expression was induced by L-arabinose and then purified using Ni-NTA affinity chromatography. The expression in E. coli was low and barely detected by Western blot assay. The in vitro multienzyme digestibility of HEAAP was around 79%, which suggests that the protein is potentially nutritious. Virtual analysis classifies the protein as unstable and hydrophilic, with a half-life in E. coli of 10 h. The recombinant HEAAP was successfully synthesized, but it is necessary to improve the digestibility and to optimize expression including selecting other expression models.

The present report was designed to determine the antioxidant and antigenotoxic effects of phaseolin (isolated from Phaseolus vulgaris) against mouse colon and liver damage induced by azoxymethane (AOM) and its colon chemopreventive effect. Eight groups with 12 mice each were utilized for an eight-week experiment: the control group was intragastrically (ig) administered 0.9% saline solution, the positive control group was intraperitoneally (ip) injected with 7.5 mg/kg AOM twice a week (weeks three and four of the experiment), three groups were ig administered each day with phaseolin (40, 200, and 400 mg/kg), and three groups were ig administered phaseolin daily (40, 200, and 400 mg/kg) plus 7.5 mg/kg AOM twice a week in weeks three and four of the experiment. The results showed that phaseolin did not produce oxidative stress, DNA damage, or aberrant crypts, in contrast, 100% inhibition of lipoperoxidation, protein oxidation, and nitrites induction generated by AOM was found in both organs, and DPPH radical capture occurred. The two highest phaseolin doses reduced DNA damage induced by AOM in both organs by more than 90% and reduced the AOM-induced aberrant crypts by 84%. Therefore, our study demonstrated the strong in vivo antioxidant, antigenotoxic, and chemopreventive potential of phaseolin.

We evaluated the duloxetine DNA damaging capacity utilizing the comet assay applied to mouse brain and liver cells, as well as its DNA, lipid, protein, and nitric oxide oxidative potential in the same cells. A kinetic time/dose strategy showed the effect of 2, 20, and 200 mg/kg of the drug administered intraperitoneally once in comparison with a control and a methyl methanesulfonate group. Each parameter was evaluated at 3, 9, 15, and 21 h postadministration in five mice per group, except for the DNA oxidation that was examined only at 9 h postadministration. Results showed a significant DNA damage mainly at 9 h postexposure in both organs. In the brain, with 20 and 200 mg/kg we found 50 and 80% increase over the control group (p ≤ 0.05), in the liver, the increase of 2, 20, and 200 mg/kg of duloxetine was 50, 80, and 135% in comparison with the control level (p ≤ 0.05). DNA, lipid, protein and nitric oxide oxidation increase was also observed in both organs. Our data established the DNA damaging capacity of duloxetine even with a dose from the therapeutic range (2 mg/kg), and suggest that this effect can be related with its oxidative potential.

Asthma is a chronic disease whose main anatomical–functional alterations are grouped into obstruction, nonspecific bronchial hyperreactivity, inflammation and airway remodeling. Currently, the Global Initiative of Asthma 2020 (GINA 2020) suggests classifying it into intermittent cases, slightly persistent, moderately persistent and severely persistent, thus determining the correct guidelines for its therapy. In general, the drugs used for its management are divided into two groups, those with a potential bronchodilator and the controlling agents of inflammation. However, asthmatic treatments continue to evolve, and notable advances have been made possible in biological therapy with monoclonal antibodies and in the relationship between this disease and oxidative stress. This opens a new path to dietary and herbal strategies and the use of antioxidants as a possible therapy that supports conventional pharmacological treatments and reduces their doses and/or adverse effects. This review compiles information from different published research on risk factors, pathophysiology, classification, diagnosis and the main treatments; likewise, it synthesizes the current evidence of herbal medicine for its control. Studies on integrative medicine (IM) therapies for asthmatic control are critically reviewed. An integrative approach to the prevention and management of asthma warrants consideration in clinical practice. The intention is to encourage health professionals and scientists to expand the horizons of basic and clinical research (preclinical, clinical and integrative medicine) on asthma control.

AIM To examine the association between weekend alcohol consumption and the biochemical and histological alterations at two different concentrations of alcohol in both genders in rats. METHODS Wistar rats weighing 170-200 g were divided into groups as follows: (1) Control groups; and (2) weekend alcohol-consumption group: 2 d/weekly per 12 wk, at two different concentrations: (1) Group of males or females with a consumption of a solution of alcohol at 40%; and (2) group of males or females with a consumption of a solution of alcohol at 5%. At the end of the experiment, serum and liver samples were obtained. The following enzymes and metabolites were determined in serum: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase, and Gamma-Glutamyltransferase, and glucose, triglycerides, cholesterol, bilirubin, and albumin. Liver samples from each group were employed to analyze morphological abnormalities by light microscopy. RESULTS In all of the weekend alcohol-consumption groups, AST activity presented a significant, 10-fold rise. Regarding ALT activity, the groups with weekend alcohol consumption presented a significant increase that was six times greater. Bilirubin levels increased significantly in both groups of females. We observed a significant increase in the parameters of fatty change and inflammation due to weekend alcohol consumption. Only the group of females that consumed alcohol at 40% presented slight hepatocellular disorganization CONCLUSION The results obtained herein provide solid evidence that weekend alcohol consumption gives rise to liver damage, demonstrated by biochemical and histological alterations, first manifested acutely, and prolonged weekend alcohol consumption can cause greater, irreversible damage.

Background: Exercise training induces adaptive physiological and morphological modifications in the entire organism, however, excessive loads of training may increase damage in tissues. The purpose of this study was to evaluate the effect of silymarin in lung and liver histological changes in rats subjected to exercise training (ET). Methods: Male Wistar rats were subjected to an 8-week ET treadmill program 5 days per week, 60 min/session, and were previously administered 100 mg ascorbic acid or 100 mg of silymarin. Results: Silymarin increased alveolar and bronchial muscle size, improve vascularization, and reduced tissue inflammation. In liver, silymarin promoted the reduction of lipid content. Conclusion: Silymarin supplementation may improve inflammation in pulmonary tissue after 8 weeks of the ET treadmill program, improve cell recovery, and reduce intrahepatic lipid content.

Grapefruit juice (GFJ) and naringin when consumed previously or together with medications may alter their bioavailavility and consequently the clinical effect. Ifosfamide (IF) is an antitumoral agent prescribed against various types of cancer. Nevertheless, there is no information regarding its interaction with the ingestion of GFJ or naringin. The aims of the present report were validating a method for the quantitation of IF in the plasma of mouse, and determine if mice pretreated with GFJ or naringin may modify the IF pharmacokinetics. Our HPLC results to quantify IF showed adequate intra and inter-day precision (RSD Cmax of IF 22.9% and 17.8%, respectively, and decreased Tmax of IF 19.2 and 53.8%, respectively. The concentration of IF was higher when GFJ (71.35 ± 3.5 µg/mL) was administered with respect to that obtained in the combination naringin with IF (64.12 ± µg/mL); however, the time required to reach such concentration was significantly lower when naringin was administered (p Tmax and decreased the Cmax of IF.

Traditional Medicine/Complementary and Alternative Medicine is a practice that incorporates medicine based on plants, animals, and minerals for diagnosing, treating, and preventing certain diseases, including chronic degenerative diseases such as obesity, diabetes, hypertension, atherosclerosis, and cancer. Different factors generate its continued acceptance, highlighting its diversity, easy access, low cost, and the presence of relatively few adverse effects and, importantly, a high possibility of discovering antigenotoxic agents. In this regard, it is known that the use of different antigenotoxic agents is an efficient alternative to preventing human cancer and that, in general, these can act by means of a combination of various mechanisms of action and against one or various mutagens and/or carcinogens. Therefore, it is relevant to confirm its usefulness, efficacy, and its spectrum of action through different assays. With this in mind, the present manuscript has as its objective the compilation of different investigations carried out with garlic that have demonstrated its genoprotective capacity, and that have been evaluated by means of five of the most outstanding tests (Ames test, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay). Thus, we intend to provide information and bibliographic support to investigators in order for them to broaden their studies on the antigenotoxic spectrum of action of this perennial plant.

Traditional Medicine/Complementary and Alternative Medicine is a practice that incorporates medicine based on plants, animals, and minerals for diagnosing, treating, and preventing certain diseases, including chronic degenerative diseases such as obesity, diabetes, hypertension, atherosclerosis, and cancer. Different factors generate its continued acceptance, highlighting its diversity, easy access, low cost, and the presence of relatively few adverse effects and, importantly, a high possibility of discovering antigenotoxic agents. In this regard, it is known that the use of different antigenotoxic agents is an efficient alternative to preventing human cancer and that, in general, these can act by means of a combination of various mechanisms of action and against one or various mutagens and/or carcinogens. Therefore, it is relevant to confirm its usefulness, efficacy, and its spectrum of action through different assays. With this in mind, the present manuscript has as its objective the compilation of different investigations carried out with garlic that have demonstrated its genoprotective capacity, and that have been evaluated by means of five of the most outstanding tests (Ames test, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay). Thus, we intend to provide information and bibliographic support to investigators in order for them to broaden their studies on the antigenotoxic spectrum of action of this perennial plant.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a powerful nuclear transcription factor that coordinates an antioxidant cytoprotector system complex stimulated by the increase in inoxidative stress (OS). In the present manuscript, we conduct a review on the evidence that shows the effect different modalities of physical exercise exert on the antioxidant metabolic response directed by Nrf2. During physical exercise, the reactive oxygen species (ROS) are increased; therefore, if the endogenous and exogenous antioxidant defenses are unable to control the elevation of ROS, the resulting OS triggers the activation of the transcriptional factor Nrf2 to induce the antioxidant response. On a molecular basis related to physical exercise, hormesis maintenance (exercise preconditioning) and adaptative changes in training are supported by a growing body of evidence, which is important for detailing the health benefits that involve greater resistance to environmental aggressions, better tolerance to constant changes, and increasing the regenerative capacity of the cells in such a way that it may be used as a tool to support the prevention or treatment of diseases. This may have clinical implications for future investigations regarding physical exercise in terms of understanding adaptations in high-performance athletes but also as a therapeutic model in several diseases.

Diabetes mellitus is the most common chronic disease worldwide that causes numerous complications, including male infertility. The prevalence of DM is 451 million people and estimated that would increase to 693 million in 2045. Fluorosis caused by drinking water contaminated with inorganic fluoride is a public health problem in many areas around the world. Previous studies have shown that fluoride exposure damages the male reproductive function. This study aimed to evaluate the fluoride sub-chronic exposure on the spermatozoa function in streptozotocin (STZ)-induced diabetic mice. After confirming diabetes by measuring blood glucose levels, the male mice received 45.2 ppm of fluoride added or deionized water. We evaluated several parameters in diabetic mice exposed to fluoride: standard quality analysis, the mitochondrial transmembrane potential (ψm), the caspase activity in spermatozoa, urinary fluoride excretion, and histological evaluation in the testes. After 60 days of fluoride-exposure, diabetic mice, significantly decreased sperm quality (motility, viability, and concentration). Spermatozoa from fluoride-exposure in diabetic mice presented a significant decrease in ψm and a significant increase in activity caspase 3/7. Urinary fluoride excretion was decreased in diabetic mice exposed to fluoride. Subchronic fluoride exposure of mice with STZ-induced diabetes aggravated testicular damage and the spermatozoa function.

The aim of this study is to characterize bone erosions in metatarsal heads (MTH) in rheumatoid arthritis (RA) and gout by grayscale ultrasound. In a descriptive, cross-sectional study, we evaluated 40 patients with RA and 40 with gout, both diagnosed according to the American College of Rheumatology/European League Against Rheumatism criteria, respectively. All patients had bone erosion demonstrated by ultrasound, which was used, following OMERACT criteria, to describe the shape, size, number, border definition, overhanging margin, topography (intra- or extra-articular), and distribution (over dorsal, medial, lateral, or plantar aspect) of the lesions in the MTH. Descriptive statistics were used and a concordance exercise between two ultrasonographers blinded to the diagnosis was performed. Bone erosions in RA were observed most frequently at the plantar and lateral aspect of the fifth MTH, round in 96 %, small-sized (2.43 ± 0.9 mm), intra-articular (100 %), and single (75 %). Few bone erosions had a well-defined border an overhanging margin while in gout were found most frequently in the medial and dorsal aspect of the first MTH, single in 71 %, intra-articular in 100 %, and of median size (4.0 ± 2.3). For shape, 51 % was round and 49 % was oval. A well-defined border was present in 39 %, and an overhanging margin in 62 %. Inter-rater reliability kappa was excellent (0.81, 95 % CI 0.56-1.00). Some characteristics of bone erosions in RA, including shape, size, ill-defined border, and localization in the fifth MTH could distinguish the lesions from gout. Grayscale US has excellent reliability to describe bone erosions in RA and gout.

(1) Background: Regular exercise induces physiological and morphological changes in the organisms, but excessive training loads may induce damage and impair recovery or muscle growth. The purpose of the study was to evaluate the impact of Silymarin (SM) consumption on endurance capacity, muscle/cardiac histological changes, bodyweight, and food intake in rats subjected to 60 min of regular exercise training (RET) five days per week. (2) Methods: Male Wistar rats were subjected to an eight-week RET treadmill program and were previously administered SM and vitamin C. Bodyweight and food consumption were measured and registered. The maximal endurance capacity (MEC) test was performed at weeks one and eight. After the last training session, the animals were sacrificed, and samples of quadriceps/gastrocnemius and cardiac tissue were obtained and process for histological analyzes. (3) Results: SM consumption improved muscle recovery, inflammation, and damaged tissue, and promoted hypertrophy, vascularization, and muscle fiber shape/appearance. MEC increased after eight weeks of RET in all trained groups, moreover, the SM-treated group was enhanced more than the group with vitamin C. There were no significant changes in bodyweight and in food and nutrient consumption along the study. (5) Conclusion: SM supplementation may enhance physical performance, recovery, and muscle hypertrophy during the eight-week RET program.

Silymarin (SM) is a mixture of flavolignans extracted from the seeds of species derived from Silybum marianum, commonly known as milk thistle or St. Mary’sthistle. These species have been widely used in the treatment of liver disorders in traditional medicine since ancient times. Several properties had been attributed to the major SM flavolignans components, identified as silybin, isosilybin, silychristin, isosilychristin, and silydianin. Previous research reported antioxidant and protective activities, which are probably related to the activation of the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), known as a master regulator of the cytoprotector response. Nrf2 is a redox-sensitive nuclear transcription factor able to induce the downstream-associated genes. The disruption of Nrf2 signaling has been associated with different pathological conditions. Some identified phytochemicals from SM had shown to participate in the Nrf2 signaling pathway; in particular, they have been suggested as activators that disrupt interactions in the Keap1-Nrf2 system, but also as antioxidants or with additional actions regarding Nrf2 regulation. Thus, the study of these molecules makes them appear attractive as novel targets for the treatment or prevention of several diseases.

Roselle (Hibiscus sabdariffa L.), also known as jamaica in Spanish, is a perennial plant that grows in tropical and subtropical regions, including China, Egypt, Indonesia, Mexico, Nigeria, Thailand, and Saudi Arabia. It has a long history of uses, mainly focused on culinary, botanical, floral, cosmetic, and medicinal uses. The latter being of great impact due to the diuretic, choleretic, analgesic, antitussive, antihypertensive, antimicrobial, immunomodulatory, hepatoprotective, antioxidant, and anti-cancer effects. These therapeutic properties have been attributed to the bioactive compounds of the plant, mainly phenolic acids, flavonoids, anthocyanins, and organic acids (citric, hydroxycitric, hibiscus, tartaric, malic, and ascorbic). Most literature reviews and meta-analyses on the therapeutic potential of Hibiscus sabdariffa L. (Hs) compounds have not adequately addressed the contributions of its organic acids present in the Hs extracts. This review compiles information from published research (in vitro, in vivo, and clinical studies) on demonstrated pharmacological properties of organic acids found in Hs. The intent is to encourage and aid researchers to expand their studies on the pharmacologic and therapeutic effects of Hs to include assessments of the organic acid components.

It has been known for years that, after chemical damage or surgical removal of its tissue, the liver initiates a series of changes that, taken together, are known as regeneration, which are focused on the recovery of lost or affected tissue in terms of the anatomical or functional aspect. The Nuclear factor-erythroid 2-related factor (Nrf-2) is a reduction-oxidation reaction (redox)-sensitive transcriptional factor, with the basic leucine Zipper domain (bZIP) motif, encoding the NFE2L2 gene. The Keap1-Nrf2-ARE pathway is transcendental in the regulation of various cellular processes, such as antioxidant defenses, redox equilibrium, the inflammatory process, the apoptotic processes, intermediate metabolism, detoxification, and cellular proliferation. Some reports have demonstrated the regulator role of Nrf-2 in the cellular cycle of the hepatocyte, as well as in the modulation of the antioxidant response and of apoptotic processes during liver regeneration. It has been reported that there is a delay in liver regeneration after Partial hepatectomy (PH) in the absence of Nrf-2, and similarly as a regulator of hepatic cytoprotection due to diverse chemical or biological agents, and in diseases such as hepatitis, fibrosis, cirrhosis, and liver cancer. This regulator/protector capacity is due to the modulation of the Antioxidant response elements (ARE). It is postulated that oxidative stress (OS) can participate in the initial stages of liver regeneration and that Nrf-2 can probably participate. Studies are lacking on the different initiation stages, maintenance, and the termination of liver regeneration alone or with ethanol.

Duloxetine is a widely used antidepressant worldwide. In the present report, we evaluated its capacity to induce micronucleated polychromatic erythrocytes (MNPEs) and micronucleated normochromatic erythrocytes (MNNEs) in mice. Two assays were performed, one with a single chemical administration and the other with daily chemical administration. In the first, we administered the antidepressant once to groups of 5 mice by the intragastric (i.g.) route (2, 20, and 200 mg/kg) and performed the analysis at 24, 48, and 72 h postadministration. A control group administered i.g. distilled water was included in the assay, as well as another treated with the micronuclei-inducing chemical daunorubicin (2.5 mg/kg, injected intraperitoneally (i.p.)). In this assay, we found significant damage induced by duloxetine starting from the first time evaluated, showing the highest MNPE increase at the end of the assay. We observed a saturation effect as well, suggested by a decreasing relative efficiency with respect to each tested dose. In a second assay, we administered the antidepressant i.g. every day for 5 weeks (2, 6, and 12 mg/kg), and micronuclei analysis was performed at the end of each week. In this study, we also found a significant increase in both MNPEs and MNNEs which was clear by the second week of administration. Our results suggest that short-term as well as cumulative damage is produced by duloxetine. Thus, confirmation of the observed genotoxic potential in other models seems advisable, as well as caution when prescribing this antidepressant.

Duloxetine is an antidepressant which has showed valuable results, particularly in patients with major depression. This type of drugs is known to require genotoxic studies as part of their preclinical safety evaluation. In the case of duloxetine, however, there have been controversial results. Therefore, we considered it worthwhile to extend studies on the matter in an attempt to reach a conclusion. The present assay was made in mouse bone marrow to evaluate the capacity of the drug to induce sister chromatid exchanges (SCE), as well as to modify the proliferation kinetics and the mitotic index. Three doses of the antidepressant were tested (2, 20, and 200 mg/kg), besides the control mice were administered with purified water, and the positive treated animals administered with 1 mg/kg of doxorubicin. The results indicated a moderate but significant increase of SCE with the three tested doses, no effect regarding the mitotic index and a small reduction in the proliferation kinetics. Although in our assay the drug showed a lower effect, the present study agreed with a previous report that analyzed the amount of micronuclei in mouse peripheral blood, and it confirmed the relevance of evaluating the genotoxic effect of antidepressants, specifically duloxetine by applying diverse tests.

Background Autonomic dysfunction, smooth muscle fibrosis and vascular damage lead to small intestinal bacterial overgrowth (SIBO) in Systemic Sclerosis (SSc). SIBO is characterized by diarrhea, abdominal pain, bloating, malabsorption and malnutrition. Objectives To evaluate by NIH PROMIS® gastrointestinal symptoms scales and SIBO by hydrogen breath test (HBT) in patients with SSc. Methods We include 68 patients with SSc (ACR-EULAR 2015) who signed informed consent. NIH PROMIS®questionarie was applied to evaluated gastrointestinal symptoms and classified in not symptomatic, least, mildy, moderately and most symptomatic. Glucose HBT was applied after 14 hours fast, oral hygiene and 30 days free of antibiotics. Patients who has a negative HBT with symptoms associated to glucose ingestion we repeat test with lactulose. Results We applied questionnaire to 58 SSc patients, age 52 (26–75)years, 65 (96%) female and 3 (4%) males, disease duration 13 (1–40) years, limited SSc 41 (59%) and diffuse 27 (41%), body mass index 24 (12–39). They are using prednisone (28%), micofenolate (14%), methotrexate (19%), azatioprin (5%), amlodipine or nifedipine (33%). Patients had continuous and very high increase of parts per millon (ppm) of exhaled Hydrogen: min0: 13 ppm (5–21), min15:17 ppm (5–43), min30:17 (3–49), min45:18ppm (7–103), min 60:22ppm (8–145), min90:18ppm (2–250), min120:25ppm (3–212), min150:71ppm (3–235). Normal values: Frequency of gastrointestinal symptoms were flatulence (87.5vs81.2%), nausea/vomiting (72.7vs37.6%), constipation (65.6vs40%), diarrhea (45.2vs33.4%), abdominal pain %) and incontinence (39.4vs31.3%) respectively between SCB (+) positive and negative. Hyperproduction of hydrogen in breath had a direct correlation to severity of their symptoms (p≤0.05). The severity of diarrhea was in close relation to the severity of its rectal incontinence (r=0.73,p=0.001), and greater abdominal pain with flatulence (r=72, p=0.001). Conclusions Gastrointestinal symptoms are common in SSc regardless of whether they have SIBO. However, a higher Row Score SGI or moderate severe status (NIH PROMIS) correlates with high H scores from the 30th minute, therefore, the questionnaire is useful within the SSc assessment. Disclosure of Interest None declared

The objective was to determine the regulatory dynamic of Nrf2 during liver regeneration and the administration of EtOH and/or the G. schiedeanum extract. Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy; they were then divided into three groups (groups 1-3). During the experiment, animals in Group 1 drank only water. The other two groups (2-3) received an intragastric dose of ethanol (1.5 g/kg BW, solution at 40% in isotonic saline solution). Additionally, rats in group 3 received a geranium extract daily at a dose of 300 mg/kg BW i.g. EtOh and/or Geranium schiedeanum was administered to rats with regenerating livers for 7 days. At the end of treatment, the activity was determined of the antioxidant enzymes, DNA concentration, TBARS, and TAC, in addition to the expression of Nrf-2, Cyclin D1, and Nqo1. EtOH increased ROS and Nrf-2, which activated the antioxidant defenses and delayed liver proliferation. On the other hand, Geranium schiedeanum exerted an antioxidant effect, diminishing ROS, but Nrf-2 expression increased, favoring liver proliferation through the increase of DNA concentration and the overexpression of Cyclin D1, however it did not activate the antioxidant defenses. In sum, it can be concluded that Nrf-2 possesses a regulatory dynamic that is evident in the presence of a toxic agent (EtOH) and/or a phytochemical agent with antioxidant capacity (Geranium schiedeanum) during liver regeneration.

Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequentl consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.

Plants belonging to the genus Opuntia spp. are the most abundant of the Cactaceae family, grown throughout America and the Mediterranean central area. Its fruit, known as cactus pear or prickly pear, is an oval berry grouped in different colors. Some studies have shown its antioxidant activities which may help in preventing chronic pathologies such as diabetes. The purpose of the study was to evaluate the antioxidant capacity of three varieties of prickly pear juice (red-purple, white-green and yellow-orange) in five different concentrations (100, 250, 500, 750, and 1000 mg/mL) by DPPH (1,1-diphenyl-2-picrylhydrazyl radical) colorimetric method, selecting the best variety to determine its anticlastogenic potential against methyl methanesulfonate (MMS). The results indicate that the highest antioxidant was found in the juice of the prickly pear red-purple variety (PPRP), in all concentrations. Its anticlastogenic potential was therefore evaluated with a micronucleus assay. The experiment was run over two weeks. A negative control was included along with a positive control with MMS (40 mg/kg), a group of mice treated with PPRP (25 mL/kg), and three groups with PPRP (in doses of 25, 16.5 and 8.3 mL/kg) plus the mutagen. The PPRP was administered daily by oral gavage and the MMS was injected intraperitoneally five days prior to the end of the experiment. Blood samples were obtained at 0, 24, 48, 72 and 96 h in order to determine the frequency of micronucleated polychromatic erythrocytes (MNPE). The results indicated that PPRP is not a genotoxic agent, on the contrary, it may reduce the number of MNPE. In this regard, the PPRP showed an anticlastogenic effect directly proportional to its concentrations. Thus, the highest protection was obtained with a concentration of 25 mL/kg after 48 h of treatment.