During Trypanosoma cruzi infection, oxidative stress is considered a contributing factor for dilated cardiomyopathy development. In this study, the effects of astaxanthin (ASTX) were evaluated as an alternative drug treatment for Chagas disease in a mouse model during the acute infection phase, given its anti-inflammatory, immunomodulating, and anti-oxidative properties. ASTX was tested in vitro in parasites grown axenically and in co-culture with Vero cells. In vivo tests were performed in BALB/c mice (4–6 weeks old) infected with Trypanosoma cruzi and supplemented with ASTX (10 mg/kg/day) and/or nifurtimox (NFMX; 100 mg/kg/day). Results show that ASTX has some detrimental effects on axenically cultured parasites, but not when cultured with mammalian cell monolayers. In vivo, ASTX did not have any therapeutic value against acute Trypanosoma cruzi infection, used either alone or in combination with NFMX. Infected animals treated with NFMX or ASTX/NFMX survived the experimental period (60 days), while infected animals treated only with ASTX died before day 30 post-infection. ASTX did not show any effect on the control of parasitemia; however, it was associated with an increment in focal heart lymphoplasmacytic infiltration, a reduced number of amastigote nests in cardiac tissue, and less hyperplasic spleen follicles when compared to control groups. Unexpectedly, ASTX showed a negative effect in infected animals co-treated with NFMX. An increment in parasitemia duration was observed, possibly due to ASTX blocking of free radicals, an anti-parasitic mechanism of NFMX. In conclusion, astaxanthin is not recommended during the acute phase of Chagas disease, either alone or in combination with nifurtimox.
Background: In the last decade, the harmful use of dioxin has been demonstrated in human health and in the whole environment. It is well known among scientists that 2, 3, 7, 8-tetrachloro dibenzo-p-dioxin (TCDD) is an environmental pollutant that causes endocrine disruption, which causes male reproductive toxicity. Objective: The objective of the present study was to evaluate the toxicity effect of low doses of TCDD in male CD1 mice. Materials and Methods: Three concentrations of TCDD (0.375, 0.75, 1.5 mg / kg) were analyzed and the effects on spermatozoa were evaluated 10 days after oral administration of the product. As bioindicators of TCDD toxicity, an exhaustive analysis of several spermatic parameters including motility, vitality, count, morphology and viability, flow cytometry was used to determine the affected sperm population by cytotoxicity and apoptosis. In addition, a morphometric analysis of testicles was performed. Results: The results show that the body weight of the treated animals was reduced in medium and high doses (0.75, 1.5 mg / kg) with respect to the control groups. In the groups treated with TCDD, the abnormal head of the sperm increased by 52.5% more than the control group. Significant differences in apoptosis were observed between the negative control and vehicle control, including the median dose (0.75 mg / kg). Conclusion: It is concluded that at these low doses there was an impact on the quality of the mouse sperm, adding an effect on apoptosis and cytotoxicity of sperm exposed to these doses of TCDD.
<p><strong>Background. </strong>Caseous lymphadenitis is a worldwide distribute disease that affects the sheep and goat industry. <em>Corynebacterium pseudotuberculosis</em> <em>ovis</em> is a facultative intracellular Gram-positive bacterium, considered the etiologic agent of the disease. Complete genome sequences of Mexican isolates have been obtained and different strain has been previously characterized. The study of virulence factors allows establishing potential candidates for the development of vaccines and diagnostic tools. <strong>Objective.</strong> To identify the complete <em>pld </em>and <em>cp40</em> genes sequence from a Mexican isolate of <em>Corynebacterium pseudotuberculosis ovis</em>, principal virulence factors. <strong>Methodology</strong>. <em>Corynebacterium pseudotube</em>rculosis isolate 2J-L was obtained from an abscess of a sheep of the State of Jalisco. The complete <em>pld </em>and <em>cp40</em> genes were amplified by PCR, cloned into a replicative vector and sequenced by Sanger automatic sequencing. Gene sequences conservancy was established, analyzing homology across previously reported genes of Mexican strains MEX1, MEX2, MEX9, MEX25 and MEX29. <strong>Results</strong>. Sequences of <em>pld</em> and <em>cp40</em> genes from isolate 2J-L presented high percentages of similarity (99%) in comparison with the sequences of other isolates of <em>Corynebacterium pseudotuberculosis</em>, reported in the GenBank database. The analysis of nucleotide sequence homology and phylogenetic tree based on <em>pld</em> and <em>cp40</em> directed the observation that 2J-L is related to Mexican strain MEX29 and MEX25. Phylogenetic results agreed on the idea that strains biovar <em>ovis</em> and biovar <em>equi</em> are groupings on different clades. Finally, results indicate that Mexican strains are more similar among strains isolated from the same host type, without geography distance influence. <strong>Implications.</strong> The analysis pointed out that both genes conserve their sequences in comparison with Mexican and international strains, which encourages the research continuity for vaccine and diagnostic tools development using proteins PLD and CP40 as antigen targets. <strong>Conclusions.</strong> The complete <em>pld</em> and <em>cp40</em> genes from Mexican isolate 2J-L were amplified, cloned and analyzed; important virulence factors from <em>Corynebacterium pseudotuberculosis</em>.</p>
The development of in vitro cytotoxicity assays has been driven by the need to rapidly evaluation of potential toxicity of large numbers of compounds, to reduce animal experimentation, and to save time and material resources. The large number of experimental results reported by different groups worldwide has lead to the accumulation of huge amounts of ontology-like data in large public databases as in ChEMBL. Conversely, many drugs have been assayed only for some selected tests. In this context, High-throughput multi-target Quantitative Structure-Activity (High-throughput mt-QSAR) techniques may become an important tool to rationalize drug discovery process. In this work, we train and validate by the first time mt-QSAR model using TOPS-MODE approach to calculate drug molecular descriptors and the software STATISTICA to seek a Linear Discriminant Analysis (LDA) function. This model correctly classifies 8,258 out of 9,000 (Accuracy = 91.76%) multiplexing assay endpoints of 7903 drugs (including both train and validation series). Each endpoint correspond to one out of 1418 assays, 36 molecular and cellular targets, 46 standard type measures, in two possible organisms (human and mouse). After that, we determined experimentally, by the first time, the values of EC50 = 21.58 μg/mL and Cytotoxicity = 23.6 % for the antimicrobial / anti-parasite drug G1 over Balb/C mouse peritoneal macrophages using flow cytometry. In addition, the model predicts for G1 only 7 positive endpoints out 1,251 cytotoxicity assays (0.56% of probability of cytotoxicity in multiple assays). Both experimental and theoretical results point to a low macrophage cytotoxicity of G1. The results obtained are very important because they complement the toxicological studies of this important drug. This work opens a new door for the "in silico" multiplexing screening of large libraries of compounds. 2 grouping of cells that are derived from monocytes. They have a multitude of functions depending on their final differentiated state. These functions range from phagocytosis to antigen presentation to bone destruction, to name a few. Their importance in both the innate and acquired immune functions is undeniable. Xenobiotics that degrade their functional status can have grave consequences. Many published reports on the effect of xenobiotics on macrophage function make comparisons between treated versus untreated macrophages isolated in an identical manner to control for this problem. A commonly used source of mouse and rat macrophages is the peritoneal cavity. Two types of macrophages from the peritoneal cavity are used, resident and elicited (Barnett J. B. and Brundage Kathleen M. 2010). Often in the cytotoxicity assay to increase the number of macrophages, a sterile irritant, such as thioglycollate, is injected several days prior to harvesting the cells. The resulting peritoneal cells are referred to as elicited macrophages. The process of cytotoxicity is the result of a sequence of stages and complex biological interactions that can be influenced by severa...
El objetivo de este estudio fue determinar la distribución sanguínea de linfocitos T CD4, CD8, LT γδ (WC1) en carneros infectados experimentalmente con Brucella ovis. Se utilizaron 18 carneros de 1 a 4 años y libres de B. ovis distribuidos en tres grupos: Control (n=6); Inoculado en las mucosas ocular y prepucial (n=6); Inoculados vía endovenosa (n=6). Se realizó el seguimiento serológico desde el día de la inoculación hasta el 189 dPI (día pos-inoculación). Se inmunotipificaron las poblaciones de linfocitos CD4 y CD8 a los 120, 150 y 189 y de WC1 (linfocitos Tγδ) a los 120 dPI por citometría de flujo. Los carneros, a partir del tercer dPI comenzaron a seroconvertir; a los 21 y 28 dPI todos los animales de los grupos inoculados por vía endovenosa y mucosa, respectivamente, resultaron positivos; asimismo, el 50% de los animales de los grupos desafiados se presentaron como positivos o sospechosos a la prueba de ELISA a los 189 dPI. Se encontraron diferencias en las Medias de Intensidad de Fluorescencia (MIF) de los linfocitos CD8 entre el grupo control (1027.4) y el grupo inoculado por vía endovenosa (499.6) a los 120 dPI (p<0.05) y en las MIF de los linfocitos CD4 entre grupos a los 189 dPI (p<0.05). Las poblaciones linfocitarias T γδ (WC1) presentaron diferencias en MIF entre el grupo control y los grupos inoculados a los 120 dPI (p<0.05). Los resultados indican que B. ovis puede modular la respuesta inmune del hospedero, que los linfocitos CD4 y CD8 son importantes para la defensa del hospedero ante esta infección, y que las poblaciones de CD4 como de CD8 pueden fluctuar durante el periodo de infección por B. ovis. Así mismo, la participación de los linfocitos T γδ podría ser un factor importante en el control de la infección causada por B. ovis.
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