Health impact assessment after Danio rerio long-term exposure to environmentally relevant concentrations of metformin and guanylurea.

The antidiabetic drug metformin (MET) and its metabolite guanylurea (GUA) have been frequently and ubiquitously detected in surface water. Consequently, there has been a consistent rise in studying the toxicity of MET and GUA in fish over the past decade. Nonetheless, it is noteworthy that no study has assessed the harmful effects both compounds might trigger on fish blood and organs after chronic exposure. Taking into consideration the data above, our research strived to accomplish two primary objectives: Firstly, to assess the effect of comparable concentrations of MET and GUA (1, 40, 100 µg/L) on the liver, gills, gut, and brain of Danio rerio after six months of flow-through exposure. Secondly, to compare the outcomes to identify which compound prompts more significant oxidative stress and apoptosis in organs and blood parameter alterations. Herein, findings indicate that both compounds induced oxidative damage and increased the expression of genes associated with apoptosis (bax, bcl2, p53, and casp3). Chronic exposure to MET and GUA also generated fluctuations in glucose, creatinine, phosphorus, liver enzymes, red and white blood count, hemoglobin, and hematocrit levels. The observed biochemical changes indicate that MET and GUA are responsible for inducing hepatic damage in fish, whereas hematological alterations suggest that both compounds cause anemia. Considering GUA altered to a more considerable extent the values of all endpoints compared to the control group, it is suggested transformation product GUA is more toxic than MET. Moreover, based on the above evidence, it can be inferred that a six-month exposure to MET and GUA can impair REDOX status and generate apoptosis in fish, adversely affecting their essential organs' functioning.

Evaluation of the safety of ethanolic extract from Piper amalago L. (Piperaceae) leaves in vivo: Subacute toxicity and genotoxicity studies.

Piper amalago L. (Piperaceae) is traditionally used due to its anti-inflammatory, analgesic, diuretic, and antiparasitic properties. However, few studies have focused on its adverse effects, compromising its safe use. This study evaluated the toxicological safety of ethanolic extract from Piper amalago leaves (EEPA), through subacute toxicity and genotoxicity assays in rodents. In subacute toxicity, 100, 200 or 300 mg/kg of EEPA were tested in female Wistar rats, by gavage, for 28 days. For genotoxicity test, female Swiss mice were orally treated with 17.5, 175 or 1750 mg/kg of EEPA and the comet, micronucleus, and splenic phagocytic assays were evaluated. In subacute toxicity, the extract induced an increase in the food and water intakes, as well as in the liver absolute weight, and in the heart and kidney relative weights. EEPA also provoked alterations in histopathological analysis of liver and in hemato-biochemical parameters, evidenced by a decrease in hematocrit levels and albumin levels, and an increase in the number of platelets and in alkaline phosphatase and cholesterol levels. However, EEPA did not presented genotoxic nor mutagenic properties. EEPA showed hemato-biochemical toxicity profile in rats and should be used with caution, especially when for prolonged period.

Diabetic Retinopathy: Important Biochemical Alterations and the Main Treatment Strategies.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by impaired glucose homeostasis, insulin resistance and hyperglycemia. Among its serious multisystemic complications is diabetic retinopathy (DR), which develops slowly and often insidiously. This disorder-the most common cause of vision loss in working-age adults-is characterized by functional and morphological changes in the retina. It results from the exacerbation of ischemic and inflammatory conditions prompted by alterations in the blood vessels, such as the development of leukostasis, thickening of the basement membrane, retinal neovascularization and fibrovascular tissue formation at the vitreoretinal interface. The pathogenic alterations are usually triggered at the biochemical level, involving a greater activity in 4 pathways: the polyol pathway, the hexosamine pathway, the formation of advanced glycation end-products and the activation of protein kinase C isoforms. When acting together, these pathways give rise to increased levels of reactive oxygen species and decreased levels of endogenous antioxidant agents, thus generating oxidative stress. All current therapies are aimed at the later stages of DR, and their application implies side effects. One possible strategy for preventing the complications of DM is to counteract the elevated superoxide production stemming from a high level of blood glucose. Accordingly, some treatments are under study for their capacity to reduce vascular leakage and avoid retinal ischemia, retinal neovascularization and macular edema. The present review summarizes the biochemical aspects of DR and the main approaches for treating it.

COVID-19 y embarazo: reporte de 15 casos / COVID-19 and pregnancy: report of 15 cases

Resumen OBJETIVO: Describir las características clínicas del embarazo, las alteraciones bioquímicas y desenlaces obstétricos de las pacientes con prueba positiva de COVID-19. MATERIALES Y MÉTODOS: Estudio observacional, de serie de casos, analítico, retrospectivo y transversal efectuado mediante la revisión de expedientes clínicos de pacientes embarazadas y cuadro clínico confirmado (mediante PCR para SARS-CoV-2) de COVID-19. RESULTADOS: Se estudiaron 15 casos de pacientes con prueba positiva para SARS-CoV-2. La media de edad fue de 28.67 años (DE ± 6.11); 14 de las 15 cursaban el tercer trimestre del embarazo, 11 de 15 tuvieran un cuadro leve de la enfermedad. La finalización del embarazo fue por cesárea en 12 de 15 pacientes y en las 3 restantes se requirió atención especializada por parte de Medicina crítica. CONCLUSIONES: Las características clínicas y la severidad de la enfermedad parecen ser similares en pacientes embarazadas y no embarazadas. El principal motivo de hospitalización y finalización del embarazo fue por causa obstétrica.

Abstract OBJECTIVE: To describe the clinical characteristics of pregnancy, biochemical alterations and obstetric outcomes of patients with positive COVID-19 test. MATERIALS AND METHODS: Observational, case series, analytical, retrospective, and cross-sectional study performed by reviewing clinical records of pregnant patients with confirmed clinical picture (by PCR for SARS-CoV-2) of COVID-19. RESULTS: Fifteen cases of patients with positive test for SARS-CoV-2 were studied. The mean age was 28.67 years (SD ± 6.11); 14 of the 15 were in the third trimester of pregnancy, 11 of 15 had mild disease. Pregnancy was terminated by cesarean section in 12 of 15 patients and 3 of 15 required specialized care by specialists in critical care medicine. CONCLUSIONS: The clinical features and severity of the disease appear to be similar in pregnant and non-pregnant patients. The main reason for hospitalization and termination of pregnancy was due to obstetric causes.

Linking stable isotopes and biochemical responses in Balanus glandula under sewage influence.

In the present study, we analyzed the influence of untreated sewage exposure on carbon (δ13C) and nitrogen (δ15N) isotopic composition and several biochemical responses in the barnacle Balanus glandula. The main objective was to evaluate whether changes in stable isotopes signature do reflect biochemical sub-lethal effects in a sewage influence gradient. Stable isotopes analysis showed differences in isotope signatures between close sewage influence and distant sites, being δ13C signatures stronger than that of δ15N. Regarding biochemical effects, although organisms close to the effluent would be clearly exposed to contaminants (increased GST activity) the oxidative stress would not be too evident (peroxidases and ACAP not affected). The most affected physiological aspect was the digestive one, reflected in increased alkaline proteases and lipases activities. A clear relation between δ15N and GST activity was found, showing to δ15N as an indicator of potential exposure to chemical contaminants.

Antecedentes familiares y diagnóstico bioquímico en 1948 formadores de cálculos renales / Family history and biochemical diagnosis in 1948 kidney stone formers

INTRODUCTION: The presence of family history of nephrolithiasis is associated with an increased risk of renal lithiasis. Different epidemiological studies have shown a family component in the incidence of it, which is independent of dietary and environmental factors. The role of heredity is evident in monogenic diseases such as cystinuria, Dent's disease or primary hyperoxaluria, while a polygenic inheritance has been proposed to explain the tendency to form calcium oxalate stones. OBJECTIVE: Our objective was to evaluate the family history of patients with renal lithiasis and the correlation of family history with its corresponding biochemical alteration, considering only those with a single metabolic alteration. METHODS: a prospective and retrospective observational and analytical study that included 1948 adults over 17 years of age and a normal control group of 165 individuals, all evaluated according to an ambulatory protocol to obtain a biochemical diagnosis. They were asked about their family history of nephrolithiasis and classified into five groups according to the degree of kinship and the number of people affected in the family. RESULTS: a positive family history of nephrolithiasis was found in 27.4% of renal stone formers, predominantly in women, compared to 15.2% of normal controls. The family history of nephrolithiasis was observed especially in 31.4% of patients with hypomagnesuria and in 29.6% of hypercalciuric patients. The rest of the biochemical alterations had a positive family history between 28.6% in hyperoxaluria and 21.9% in hypocitraturia. The highest percentage of family history of nephrolithiasis was found in cystinuria (75%) although there were few patients with this diagnosis. CONCLUSIONS: the inheritance has a clear impact on urolithiasis independently of the present biochemical alteration. Family history of nephrolithiasis of the first and second degree was observed between 21 and 32% of patients with renal lithiasis, with hypercalciuria and hypomagnesuria being the biochemical alterations with more family history

INTRODUCCIÓN: La presencia de antecedentes familiares de nefrolitiasis se asocia con un mayor riesgo de litiasis renal. Diferentes estudios epidemiológicos han mostrado un componente familiar en la incidencia de la misma, que es independiente de los factores dietéticos y ambientales. El papel de la herencia es evidente en enfermedades monogénicas como la cistinuria, la enfermedad de Dent o la hiperoxaluria primaria, mientras que se ha propuesto una herencia poligénica para explicar la tendencia a la formación de cálculos de oxalato de calcio. OBJETIVO: Nuestro objetivo fue evaluar la historia familiar de los pacientes con litiasis renal y la correlación de los antecedentes familiares con su correspondiente alteración bioquímica, considerando solo aquellos con una única alteración metabólica. MATERIAL Y MÉTODOS: Estudio observacional y analítico prospectivo y retrospectivo que incluyó a 1948 adultos mayores de 17 años y un grupo control normal de 165 individuos, evaluados todos siguiendo un protocolo ambulatorio para obtener un diagnóstico bioquímico. Se les preguntó acerca de su historia familiar de nefrolitiasis y se clasificó en cinco grupos según el grado de parentesco y el número de personas afectadas en la familia. Resultados: Se encontró historia familiar positiva de nefrolitiasis en el 27,4% de los formadores de cálculos renales, predominando en mujeres, frente al 15,2% de los controles normales. La historia familiar de nefrolitiasis se observó especialmente en el 31,4% de los pacientes con hipomagnesuria y en el 29,6% de los hipercalciúricos. El resto de las alteraciones bioquímicas tuvo antecedentes familiares positivos entre el 28,6% en la hiperoxaluria y el 21,9% en la hipocitraturia. El porcentaje más alto de antecedentes familiares de nefrolitiasis se encontró en la cistinuria (75%) aunque hubo pocos pacientes con este diagnóstico. CONCLUSIONES: La herencia tiene un claro impacto en la urolitiasis independientemente de la alteración bioquímica presente. Se observan antecedentes familiares de nefrolitiasis de primer y segundo grado entre el 21 y 32% de los pacientes con litiasis renal, siendo la hipercalciuria y la hipomagnesuria las alteraciones bioquímicas con más antecedentes familiares

Clinical, hematological and biochemical alterations in hamster (Mesocricetus auratus) experimentally infected with Leishmania infantum through different routes of inoculation.

BACKGROUND: Leishmaniasis remains among the most important parasitic diseases in the developing world and visceral leishmaniasis (VL) is the most fatal. The hamster Mesocricetus auratus is a susceptible model for the characterization of the disease, since infection of hamsters with L. infantum reproduces the clinical and pathological features of human VL. In this context, it provides a unique opportunity to study VL in its active form. The main goal of this study was to evaluate the clinical, biochemical, and hematological changes in male hamsters infected through different routes and strains of L. infantum. METHODS: In the current study, hamsters (Mesocricetus auratus) were infected with the L. infantum strains (WHO/MHOM/BR/74/PP75 and MCAN/BR/2008/OP46) by intradermal, intraperitoneal and intracardiac routes. The animals were monitored for a nine month follow-up period. RESULTS: The hamsters showed clinical signs similar to those observed in classical canine and human symptomatic VL, including splenomegaly, severe weight loss, anemia, and leucopenia. Therefore the OP46 strain was more infective, clinical signs were more frequent and more exacerbated in IC group with 80 to 100 % of the animals showing splenomegaly, in the last month infection. Additionally, desquamation, hair loss and external mucocutaneous lesions and ulcers localized in the snout, accompanied by swelling of the paws in all animals, were observed. Consequently, the animals presented severe weight loss/cachexia, hunched posture, an inability to eat or drink, and non-responsiveness to external stimuli. Furthermore, regardless of strain, route of inoculum and time assessed, the animals showed renal and hepatic alterations, with increased serum levels of urea and creatinine as well as elevated serum levels of aspartate aminotransferase and alanine aminotransferase. CONCLUSIONS: These results strongly suggest that the inoculation through the intracardiac route resulted in a higher severity among infections, especially in the sixth and ninth month after infection via intracardiac, exhibited clinical manifestations and biochemical/hematological findings similar to human visceral leishmaniasis. Therefore, we suggest that this route must be preferentially used in experimental infections for pathogenesis studies of VL in the hamster model.

Biochemical and histological changes in liver of Nectomys squamipes naturally infected by Schistosoma mansoni / Alterações na bioquímica e histologia do fígado de Nectomys squamipes naturalmente infectado por Schistosoma mansoni

The South American water rat Nectomys squamipes is a wild mammal reservoir of Schistosoma mansoni in Brazil. In the present study, wild rodents were collected in the field and categorized into two groups: infected and uninfected by S. mansoni. Blood was collected to analyze changes in the serum glucose level (mg/dL) and liver fragments were used to determine the hepatic glycogen content (mg of glucose/g tissue). The histological examination showed inflammatory granulomatous lesions in different phases of development in the liver of rodents naturally infected with S. mansoni, in some cases with total or partial occlusion of the vascular lumen. Early lesions were characterized by the presence of inflammatory infiltrate around morphologically intact recently deposited eggs. Despite the significance of these histological lesions, the biochemical changes differed in extent. N. squamipes naturally infected by S. mansoni showed no variation in hepatic glycogen reserves. These findings were accompanied by a significant increase in plasma glucose contents, probably as a consequence of amino acids deamination, which are degraded, resulting in the formation of intermediates used as precursors for the glucose formation, without compromising the reserves of liver glycogen. In the wild, naturally infected N. squamipes can maintain S. mansoni infections without undergoing alterations in its carbohydrate metabolism, which minimizes the deleterious effects of S. mansoni.

Nectomys squamipes é um mamífero silvestre reservatório de Schistosoma mansoni no Brasil. No presente estudo, os roedores silvestres, colhidos no campo, foram classificados em dois grupos: infectado e não infectado por S. mansoni. O sangue foi colhido para análise da alteração no nível de glicose sérico (mg/dL) e fragmentos de fígado foram usados para determinar o conteúdo de glicogênio hepático (mg de glicose/g tecido). A análise histológica demonstrou lesões granulomatosas em diferentes fases de desenvolvimento no tecido hepático dos roedores naturalmente infectados com S. mansoni, localizados principalmente na região periportal, com total ou parcial oclusão do lúmen vascular. As lesões foram caracterizadas por presença de infiltrado inflamatório ao redor de ovos morfologicamente intactos recentemente depositados. Apesar da grande significância das lesões histológicas, as alterações bioquímicas não diferiram no mesmo grau. N. squamipes naturalmente por S. mansoni não apresentaram variação na reserva de glicogênio hepático. Esses achados foram acompanhados pelo aumento significativo nos conteúdos de glicose plasmática, provavelmente como consequência ao processo desaminativo de aminoácidos, que passam a ser degradados notadamente para a formação de glucose, sem contudo comprometer a reserva de glicogênio hepático. Em condições naturais a infecção de S. mansoni pode ser mantida usando N. squamipes como hospedeiro definitivo, sem alterações significativas nos conteúdos de glicogênio hepático, minimizando os efeitos deletérios causados por S. mansoni nos roedores N. squamipes naturalmente infectados.

Biochemical and histological changes in liver of Nectomys squamipes naturally infected by Schistosoma mansoni

The South American water rat Nectomys squamipes is a wild mammal reservoir of Schistosoma mansoni in Brazil. In the present study, wild rodents were collected in the field and categorized into two groups: infected and uninfected by S. mansoni. Blood was collected to analyze changes in the serum glucose level (mg/dL) and liver fragments were used to determine the hepatic glycogen content (mg of glucose/g tissue). The histological examination showed inflammatory granulomatous lesions in different phases of development in the liver of rodents naturally infected with S. mansoni, in some cases with total or partial occlusion of the vascular lumen. Early lesions were characterized by the presence of inflammatory infiltrate around morphologically intact recently deposited eggs. Despite the significance of these histological lesions, the biochemical changes differed in extent. N. squamipes naturally infected by S. mansoni showed no variation in hepatic glycogen reserves. These findings were accompanied by a significant increase in plasma glucose contents, probably as a consequence of amino acids deamination, which are degraded, resulting in the formation of intermediates used as precursors for the glucose formation, without compromising the reserves of liver glycogen. In the wild, naturally infected N. squamipes can maintain S. mansoni infections without undergoing alterations in its carbohydrate metabolism, which minimizes the deleterious effects of S. mansoni.

Nectomys squamipes é um mamífero silvestre reservatório de Schistosoma mansoni no Brasil. No presente estudo, os roedores silvestres, colhidos no campo, foram classificados em dois grupos: infectado e não infectado por S. mansoni. O sangue foi colhido para análise da alteração no nível de glicose sérico (mg/dL) e fragmentos de fígado foram usados para determinar o conteúdo de glicogênio hepático (mg de glicose/g tecido). A análise histológica demonstrou lesões granulomatosas em diferentes fases de desenvolvimento no tecido hepático dos roedores naturalmente infectados com S. mansoni, localizados principalmente na região periportal, com total ou parcial oclusão do lúmen vascular. As lesões foram caracterizadas por presença de infiltrado inflamatório ao redor de ovos morfologicamente intactos recentemente depositados. Apesar da grande significância das lesões histológicas, as alterações bioquímicas não diferiram no mesmo grau. N. squamipes naturalmente por S. mansoni não apresentaram variação na reserva de glicogênio hepático. Esses achados foram acompanhados pelo aumento significativo nos conteúdos de glicose plasmática, provavelmente como consequência ao processo desaminativo de aminoácidos, que passam a ser degradados notadamente para a formação de glucose, sem contudo comprometer a reserva de glicogênio hepático. Em condições naturais a infecção de S. mansoni pode ser mantida usando N. squamipes como hospedeiro definitivo, sem alterações significativas nos conteúdos de glicogênio hepático, minimizando os efeitos deletérios causados por S. mansoni nos roedores N. squamipes naturalmente infectados.

Influence of chromium salts on increased lipid peroxidation and differential pattern in antioxidant metabolism in Pistia stratiotes L

In this work, the changing effect of different concentrations (0, 0.01, 0.1, 1, 10mM) of hexavalent and trivalent chromium on different biochemical parameters along with antioxidant enzymes was investigated on water lettuce (Pistia stratiotes L.) in order to know the possible involvement of this metal in oxidative injury, besides the activities of antioxidant enzymes leading to biochemical and oxidative aberration induced by elevated concentrations. Both in roots and shoots, Cr produced a significant increase in enzymic and non-enzymic antioxidants, except in catalase (CAT) activity where a strong accumulation of hydrogen peroxide was indicated, suggesting an imposition of oxidative stress. The observation showed an uptake of chromium by P. stratiotes L. as well as increase in activity of antioxidants, as the concentrations and their duration of treatment increased. The activity of antioxidative enzymes determined the steady-state levels of ROS in the cell. The augmentation of antioxidative defense plays a key role in regulating the oxidative stress. This pointed to the possibility in induction of oxidative stress, with the increasing lipid peroxidation, followed by a differential pattern in antioxidant metabolisms by chromium ions in P. stratiotes L.