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Embryonic toxico-pathological effects of meglumine antimoniate using a chick embryo model.

ABSTRACT: Leishmaniasis is one of the diverse and neglected tropical diseases. Embryo-toxicity of drugs has always been a major concern. Chick embryo is a preclinical model relevant in the assessment of adverse effects of drugs. The current study aimed to assess embryonic histopathological disorders and amniotic fluid biochemical changes following meglumine antimoniate treatment. The alteration of vascular branching pattern in the chick's extra-embryonic membrane and exploration of molecular cues to early embryonic vasculogenesis and angiogenesis were also quantified. Embryonated chicken eggs were treated with 75 or 150 mg/kg of meglumine antimoniate. Embryo malformations, growth retardation and haemorrhages on the external body surfaces were accompanied by histopathological lesions in the brain, kidney, liver and heart in a dose-dependent manner. Significant rise occurred in the biochemical indices of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and amylase in the amniotic fluid. Quantification of the extra-embryonic membrane vasculature showed that the anti-angiogenic and anti-vasculogenic effects of the drug were revealed by a significant decrease in fractal dimension value and mean capillary area. The relative expression levels of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 mRNA also significantly reduced. Concerns of a probable teratogenicity of meglumine antimoniate were established by data presented in this study. It is concluded that tissue lesions, amniotic fluid disturbance, altered early extra-embryonic vascular development and gene expression as well as the consecutive cascade of events, might eventually lead to developmental defects in embryo following meglumine antimoniate treatment. Therefore, the use of meglumine antimoniate during pregnancy should be considered as potentially embryo-toxic. Hence, physicians should be aware of such teratogenic effects and limit the use of this drug during the growing period of the fetus, particularly in rural communities. Further pharmaceutical investigations are crucial for planning future strategies.

SUBMITTER: Khosravi A

PROVIDER: S-EPMC5969735 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Hemodynamic mechanical cues play a critical role in the early development and functional maturation of cardiomyocytes (CM). Therefore, tissue engineering approaches that incorporate immature CM into functional cardiac tissues capable of recovering or replacing damaged cardiac muscle require physiologically relevant environments to provide the appropriate mechanical cues. The goal of this work is to better understand the subcellular responses of immature cardiomyocytes using an in vitro cardiac cell culture model that realistically mimics in vivo mechanical conditions, including cyclical fluid flows, chamber pressures, and tissue strains that could be experienced by implanted cardiac tissues. Cardiomyocytes were cultured in a novel microfluidic cardiac cell culture model (CCCM) to achieve accurate replication of the mechanical cues experienced by ventricular CM. Day 10 chick embryonic ventricular CM (3.5 × 10(4) cell clusters per cell chamber) were cultured for 4 days in the CCCM under cyclic mechanical stimulation (10 mmHg, 8-15% stretch, 2 Hz frequency) and ventricular cells from the same embryo were cultured in a static condition for 4 days as controls. Additionally, ventricular cell suspensions and ventricular tissue from day 16 chick embryo were collected and analyzed for comparison with CCCM cultured CM. The gene expressions and protein synthesis of calcium handling proteins decreased significantly during the isolation process. Mechanical stimulation of the cultured CM using the CCCM resulted in an augmentation of gene expression and protein synthesis of calcium handling proteins compared to the 2D constructs cultured in the static conditions. Further, the CCCM conditioned 2D constructs have a higher beat rate and contractility response to isoproterenol. These results demonstrate that early mechanical stimulation of embryonic cardiac tissue is necessary for tissue proliferation and for protein synthesis of the calcium handling constituents required for tissue contractility. Thus, physiologic mechanical conditioning may be essential for generating functional cardiac patches for replacement of injured cardiac tissue.

Project description:Early colonization of intestinal microbiota plays an important role in intestinal development. However, the microbial succession at an embryonic stage and its assembly patterns induced by prenatal nutrition are unknown. In the present study, we used a chick embryo model to investigate the effects of in ovo feeding (IOF) of L-arginine (Arg) on the intestinal development and microbial succession of embryos. A total of 216 fertile eggs were randomly distributed into 2 groups including the non-injected control group and IOF of Arg group with 7 mg/egg. The results showed that IOF Arg increased the intestinal index, absolute weight of jejunum, and improved jejunal morphology in terms of villus width and surface area (p < 0.05). The relative mRNA expressions of mTOR and 4E-BP1 were up-regulated and accompanied by higher contents of Mucin-2 in the Arg group (p < 0.05). There was a significant elevation in contents of serum glucose and high-density lipoprotein cholesterol, whereas there was a decreased low-density lipoprotein cholesterol in the Arg group (p < 0.05). Additionally, Proteobacteria and Firmicutes were major intestinal bacteria species at the embryonic stage. However, Arg supplementation targeted to shape assembly patterns of microbial succession and then changed microbial composition (p = 0.05). Meanwhile, several short-chain fatty acids (SCFAs)-producing bacteria, such as Roseburia, Blautia, and Ruminococcus were identified as biomarkers in the Arg group (LDA > 3, p < 0.05). Accordingly, significant elevated concentrations of SCFAs, including lactic acid and formic acid, were observed in the Arg group (p < 0.05), accompanied by the higher concentration of butyric acid (0.05 < p < 0.10). In conclusion, prenatal Arg supplementation improved embryonic intestine development by regulating glucose and lipid homeostasis to supply more energy for chick embryos. The possible mechanism could be the roles of Arg in shaping the microbial assembly pattern and succession of the embryonic intestine, particularly the enrichment of potential probiotics. These findings may contribute to exploring nutritional strategies to establish health-promoting microbiota by manipulating prenatal host-microbe interactions for the healthy development of neonates.

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Embryonic toxico-pathological effects of meglumine antimoniate using a chick embryo model.

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