Neurological disorders have become more common and prevalent. Cellular pathology and behavioural symptoms in neurodegenerative diseases although connected are still a mystery to solve with no complete cure available yet. Central pathways in neurodegeneration involves impaired ubiquitin-proteasome machinery, autophagy and mitochondrial oxidative stress. In the case of neurodevlopmental disorders, environmental toxins and genetic factors are main causative agents. We aim to create a toxicity induced zebrafish model of neurological disease focussing on cognition, movement and hyperactivity disorders. Zebra fish embryos at 48 hr post fertilization were treated with different doses of lead, cholesterol and acetyl choline and by 7 days post fertilization pectoral fin movement, swimming behaviour and touch response were compromised in parallel with apoptosis identified in the brain by acridine orange fluorescent staining. A marked window is observed, therefore promising for a drug screening platform. Further characterization of pathology associated protein expression and specific behavioural studies could render this as a simple promising toxic model for preclinical drug screening.
Implantation of biomaterials poses a huge risk of local inflammation therefore affecting the implant function leading to mortality in a significant number of cases. Thus, alternatively, naturally derived drugs if developed to treat implant induced inflammation, would therefore sharply decrease the largest risk of implant rejection. This study was aimed to investigate the anti inflammatory effect of Withania somnifera on stainless steel implant induced inflammation in adult zebrafish model. Fish were divided into four experimental groups of 6 fish each. Group 1 served as the control; Group 2 fish were stainless steel implant (SSI) inserted fish without treatment; Group 3 fish were SSI inserted + Thin layer chromatography (TLC) separated portion of supernatant of W. somnifera and Group 4 fish were SSI inserted + Ibuprofen treated. Fish were assessed for reduced inflammation by histopathology, local apoptosis using fluorescent quantification, reverse transcriptase polymerase chain reaction (RT-PCR) of inflammatory genes. The characterization of the TLC separated portion of the supernatant of W. somnifera was also performed. The histopathology result of Group 2 showed crypt architectural distortion in the muscle which was not found in the control fish, whereas simultaneously TLC separated portion of the supernatant of W. somnifera showed reduced fatty changes and fibrosis of the submucosa, muscular hyperplasia. RT-PCR result revealed that the TLC separated portion of supernatant of W. somnifera has a significant inhibition of TNFα in the adult zebrafish. In conclusion the observed anti-inflammatory activity of TLC separated portion of the supernatant of W. somnifera might be due to rich phenolic acids and flavonoids.
Zebrafish (Danio rerio) has been an important model organism in a variety of biological disciplines. Presently it is well suited for studies in genetics, toxicology, behavioural neuroscience and developmental biology. Zebrafish embryos exhibit unique characteristics, including ease of maintenance and drug administration, short reproductive cycle, and embryo transparency that permits visual assessment of developing cells and organs. Because of these advantages, zebrafish bioassays are cheaper and faster than mouse assays, and are suitable for large-scale drug screening. In the present study, we investigate bioavailability of different drugs in adult zebrafish and compared our studies with fish fry. The effect of drug compounds on fish fry and in blood and liver of adult zebrafish were studied through thin layer chromatography (TLC). We hopeful that the use of these techniques or methods will make the zebrafish a prominent model in drug discovery and development research in the forthcoming years.
ABSTRACT The zebrafish is no doubt a powerful model organism with a combination of forward and reverse genetics, low cost, amenable high throughput, and rapid in vivo analysis. With these unique features, it can be expected that the zebrafish will become more frequently used for drug discovery. This review outlines the potential of zebrafish to contribute to drug discovery through the identification of novel drug targets, validation of those targets and screening for new therapeutic compounds and assay development. Keywords: Zebrafish, Drug screening, Drug target, Development.
Lung adenocarcinoma is the most common subtype of Non small cell lung cancer in which the PI3K/Akt cascade is frequently deregulated. The ubiquitous expression of the PI3K and the frequent inactivation of PTEN accounts for the prolonged survival, evasion of apoptosis and metastasis in cancer. This has led to the development of PI3K inhibitors in the treatment of cancer. Synthetic PI3K inhibitors undergoing clinical and preclinical studies are toxic in animals. Hence, there is a critical need to identify PI3K inhibitor(s) of natural origin. The current study aims to explore the efficacy of the red algae Gelidiella acerosaon inhibition of cell proliferation, migration and the expression of cell survival genes in lung adenocarcinoma cell line A549.The phytoconstituents of Gelidiella acerosa were extracted sequentially with solvents of different polarity, screened qualitatively and quantitatively for secondary metabolites and characterized by GC-MS. The in-vitro studies were performed to check the efficacy of the extract on cell proliferation (MTT assay), cell invasion (scratch assay and colony formation assay), apoptosis (fluorescent, confocal microscopy and flow cytometry) and expression of apoptosis and cell survival proteins including PI3K, Akt and GSK3β and matrix metalloproteinase MMP2 and MMP9 by Western blot method. The antitumor activity of GAE was analyzed in a tumor model of Zebrafish.The outcomes of the in vitro analysis showed an inhibition of cell proliferation, induction of apoptosis, inhibition of cell migration and colonization by the crude extract. The analysis of protein expression showed the activation of caspases 3 and Pro apoptotic protein Bax accompanied by decreased expression of Bcl-2 and Bcl-XL. On the other hand, subsequent activation of GSK3β and down regulation of PI3K, Akt were observed. The decreased expression of MMP2 correlated with the antimetastatic activity of the extract. The in vivo studies showed an inhibition of tumor growth by GAE in Zebrafish.The phytoconstituents of algal extract contributed to the anticancer properties as evidenced by in vitro and in vivo studies. These phytoconstituents can be considered as a natural source of PI3K/Akt inhibitor for treatment of cancers involving the PI3K cascade.
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