Preliminary Studies of the Toxicity of Agaricus Bisporous Aqueous Enzymatic Extracts (AbAEE) In Rats

The health benefits of extracts from Agaricus bisporus greatly extend its use as components of new functional foods for the treatment and prevention of diseases, rather than restricting it to a good food with high nutritional value and good flavor. A. bisporus aqueous enzymatic extracts (AbAEE) have unique flavor, good taste, and health benefits which makes it a good candidate for its incorporation in different matrices for development of new functional foods and nutraceuticals. The potential use of AbAEE as nutraceutical or incorporated as a part of new functional foods requires its characterization and a subsequent food safety study. The focus of this paper was to carry out a preliminary toxicological study on experimental animals (rats in this case) by acute and sub-chronic oral administration. To evaluate potential adverse effects of AbAEE at high doses the acute toxic class method was used. After administration of the preset doses, behavior changes, toxic symptoms, and deaths were observed continuously for 1 h after treatment and then intermittently at 4th, 8th and 24th h. After these initial observations, the rats were further observed for up to 14 consecutive days for any signs of toxicity and/or death. Because of the likelihood that the results obtained in this preliminary acute toxicity test have a direct relevance for protecting human health with respect to the use of AbAEE as a functional food or nutraceutial, an additional upper dose level of 5000 mg/kg b.wt. was used. Since no death was observed, the LD50 could not be estimated but is expected to exceed 5000 mg/kg and this extract could be classified as hazard category 5 (in Globally Harmonized Classification System for Chemical Substances and Mixtures.) or even unclassified for its acute toxicity by the oral route. The sub-chronic oral toxicity study of AbAEE (250 and 500 mg/kg b.wt. day) did not induce significant alterations in almost all hematological and biochemical parameters in rats. Therefore, the overall results of the present study provide supportive data on the use of AbAEE and provide a promising first step for their use as component of new functional foods or as nutraceutical. Though, further studies in both, animals and humans are needed for better evaluation of the food safety of this extract.Ministerio de Economía y Competitividad (MINECO). España IPT- 2011-1418-060000FEDER IPT- 2011-1418-06000

Nutritional quality of the most consumed varieties of raw and cooked rice in Spain submitted to an in vitro digestion model

Rice is one of the most consumed staple foods around the world and its trade is highly globalized. Increased environmental pollution generates a large amount of waste that, in many cases, is discarded close to culture fields. Some species are able to bioaccumulate toxic substances, such as metals, that could be transferred to the food chain. The main goal of this study was to evaluate the content of metallic (Al, Cd, Pb, and Cr) and metalloid elements (As) in 14 of the most consumed varieties of rice in Spain and their effects on human health. The samples were cooked, and human digestion was simulated by using a standard in vitro digestion method. Metallic and metalloid element levels were analysed by Inductively Coupled Plasma Optical Emission Spectrometry (ICPOES), previous called microwave digestion. Both the human health risk index, Hazard Quotient, and Lifetime Cancer Risk did not show toxic values in any case. Rice with a higher non-digestible fraction showed a higher liberation of proteins and a lower glycemic index. There were no significant differences in the concentrations of metallic and metalloid elements in cooked rice or in the digestible fraction in all varieties analysed. However, Al concentrations were higher than other metals in all varieties studied due to its global distribution. No relationship has been observed between the digestibility of rice and the bioaccessibility of each metallic and metalloid element. All of the studied rice varieties are healthy food products and its daily consumption is safe. The regular monitoring of metals and As in rice consumed in Spain may contribute to improvements in the human health risk evaluation.Universidad de Sevilla VIPPIT-2021-I.

Validation of a simple method for the determination of glyphosate and aminomethylphosphonic acid in human urine by UPLC-MS/MS

Environmental pollutants such as pesticides can be detrimental to human health and/or to the environment. Their excessive use may produce toxicity through various mechanisms. Glyphosate is a broad-spectrum herbicide with a high worldwide distribution. Due to this, this chemical is classified as a ‘Group 2A – probably carcinogenic to humans’ by the International Agency for Research on Cancer. Human biomonitoring is considered the golden standard for exposure assessment and provides a very useful tool in public health. Therefore, it is important to develop methods to determine traces of this herbicide and its metabolite, aminomethyl phosphonic acid, in human biological samples. A new method for glyphosate and aminomethyl phosphonic acid determination in human urine is herein described and discussed. It is based on the derivatization procedure with Fluorenylmethoxycarbonyl chloride and quantification by ultra-performance liquid chromatography-tandem mass spectrometry. The method was optimized and suitably validated, with a linear range from 1 to 20 µg L−1 in the case of glyphosate and 0.5–20 µg L−1 for aminomethyl phosphonic acid. Limits of detection and quantification were 0.5 and 1 µg L−1 for glyphosate and 0.1 and 0.5 µg L−1 for aminomethyl phosphonic acid, respectively. Mean relative recoveries ranged 108–109% for glyphosate and 104–119% for aminomethyl phosphonic acid and intermediate precision values varied from 11.90 to 12.70% for glyphosate and 4.8–9% for aminomethyl phosphonic acid. The validated method has been applied in human urine from female farmers indirectly exposed to pesticides. This procedure can be used to monitor potential exposure of humans to glyphosate and aminomethyl phosphonic acid in epidemiological studies and for routine controls in public health.Agencia estatal de investigación PID2019-106442RB-C21 / AEI / 10.13039 / 501100011033Prevent Foundation (FIUS: 3396/0828

THDP17 decreases ammonia production through glutaminase inhibition. A new drug for hepatic encephalopathy therapy

Ammonia production is implicated in the pathogenesis of hepatic encephalopathy (HE), being intestinal glutaminase activity the main source for ammonia. Management of ammonia formation can be effective in HE treatment by lowering intestinal ammonia production. The use of glutaminase inhibitors represents one way to achieve this goal. In this work, we have performed a search for specific inhibitors that could decrease glutaminase activity by screening two different groups of compounds: i) a group integrated by a diverse, highly pure small molecule compounds derived from thiourea ranging from 200 to 800 Daltons; and ii) a group integrated by commonly use compounds in the treatment of HE. Results shown that THDP-17 (10 µM), a thiourea derivate product, could inhibit the intestinal glutaminase activity (57.4±6.7%). Inhibitory effect was tissue dependent, ranging from 40±5.5% to 80±7.8% in an uncompetitive manner, showing Vmax and Km values of 384.62 µmol min−1, 13.62 mM with THDP-17 10 µM, respectively. This compound also decreased the glutaminase activity in Caco-2 cell cultures, showing a reduction of ammonia and glutamate production, compared to control cultures. Therefore, the THDP-17 compound could be a good candidate for HE management, by lowering ammonia productio

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Estudio de la oxidación de proteínas en ratas con encefalopatía hepática: una aproximación proteómica

En esta Tesis se ha estudiado el efecto del estrés oxidativo inducido por un estado de hiperamonemia, utilizando como modelo animal ratas con derivación porto-cava (ratas-dpc). El objetivo principal ha sido ver como se afecta la expresión de proteínas e

Impact of Pesticide Exposure among Rural and Urban Female Population. An Overview

Pesticides are substances that have become widely used in agriculture and the human exposure to these substances may cause adverse health outcomes. Non-occupational exposure to them can come from many sources, such as food or water. For occupational exposure, many studies have been conducted in men, as they have been mostly in charge of work related to these substances. Nonetheless, the information available concerning the exposure in women is very scarce. In addition, an important differentiation between rural and urban areas has been established, rural areas being known as the most exposed ones due to plantation fields. However, the application of higher concentrations of herbicides in small urban areas is taking a lot of importance currently as well. Regardless of gender, the conditions of exposure, and the environment, the exposure to these pesticides can have different effects on health from early life stages, resulting in different outcomes ranging from neurodevelopmental effects in newborns to different types of cancers. In this review, we discussed the toxicity of the most commonly used pesticides and the main impact on the health of the general population, focusing mainly on the effect in women from both rural and urban areas, and the different stages of development, from pregnancy or lactation to the outcomes of these exposures for their children

Preparación de quitina fúngica a partir de subproductos de hongos comestibles (Agaricus bisporus)

El extracto de quitina-oligosacáridos para su uso como posible inductor requiere abundantes materiales ricos en quitina, fácilmente disponibles y baratos. Para este propósito, la producción de fracciones enriquecidas de quitina, a partir de subproductos de la industria de procesamiento de hongos comestibles es de gran interés si se desarrollaran procedimientos apropiados. Los métodos tradicionales para la preparación comercial de quitina implican un tratamiento alternativo con ácido clorhídrico y álcali, seguido de una etapa de blanqueo con reactivos químicos para obtener un producto incoloro. Estos procesos son altamente contaminantes. Por lo tanto, los métodos con procesos amigables con el medio ambiente son de gran interés. En este trabajo informamos los resultados preliminares obtenidos con un procedimiento enzimático, amigable con el medio ambiente, basado en el uso de proteasas y glucanasas que conducen a la fracción de quitina fúngica con una concentración de quitina> 80 ± 2%, tras un proceso de desacetilación se obtiene quitosano, los cuales son compuestos de interés industrial utilizados para la liberación de fármacos, apósitos para heridas o biopelículas, entre otros y debido a que la quitina es un polímero natural es biocompatible y biodegradable en el cuerpo, y puede ser utilizada para aplicaciones biomédicas y farmacéuticas.

Assessment of the oxidative status in mother-child couples from Seville (Spain): A prospective cohort study

Pregnancy requires a high demand of energy, which leads to an increase of oxidative stress. The aim of this study was to assess the oxidative status in 200 couples of pregnant women-newborns at the time of delivery, for the first time, who gave birth in two University Hospitals from the province of Seville. Recruited women filled an epidemiological questionnaire with their demographic characteristics and dietary habits during pregnancy. At the time of delivery, both maternal and cord blood samples were collected. Protein oxidation, superoxide dismutase, and catalase levels were measured to assess the oxidative status of these women, together with the levels of vitamins D, B12, Zn, Se, and Cu. Our results showed a tendency for all biomarkers measured to be higher in cord blood than in maternal blood. For the correlations established between the OS markers and sociodemographic characteristics, only significant differences for carbonyl groups values were found on both maternal and cord blood, relating these higher values to the use of insecticides in the women’s homes. For newborns, only a significant correlation was detected between antioxidant enzymes and the newborn’s weight, specifically for superoxide dismutase activity. Additionally, the higher values obtained in cord blood might suggest metabolization, while a higher production of ROS and antioxidant enzymes might be required to maintain the balance. Measured levels for Se were similar in both maternal and cord blood, unlike Cu and Zn, where higher levels were found for maternal blood than cord blood, indicating a correlation between maternal Se values and SOD as OS biomarker. Furthermore, vitamin D levels were around the optimum values established, finding a relationship between vitamin D and new-born’s height, unlike for vitamin B12 values, where a correlation with maternal food consumption characteristics was established. Overall values were inside normal ranges and consistent for our population.Ministerio de Ciencia e Innovación y Agencia Estatal de Investigación de España. MCIN/AEI/10.13039/501100011033 - PID2019-106442RB-C2