ABSTRACT
Synthetic cannabinoids are currently a class of new psychoactive substances with the largest variety and most abused. Metabolite identification research can provide basic data for monitoring synthetic cannabinoids abuse, which is the current research hotspot. The main trend of structural modification of synthetic cannabinoid is to replace the fluorine atom on pentyl indole or indazole cyclopentyl with hydrogen atom, which greatly improves the biological activity of the compound. The main metabolic reactions include hydroxylation, fluoropentyl oxidative, ester hydrolyze, amide hydrolysis. Liquid chromatography-high resolution mass spectrometry has become the preferred choice for the structural identification of metabolites. This review mainly summarizes research on metabolism software prediction and human hepatocyte model, human liver microsomes model, rat in vivo model, zebrafish model and fungus C. elegans model in metabolite identification based on the structure and classification of synthetic cannabinoids.
Subject(s)
Animals , Rats , Caenorhabditis elegans , Cannabinoids , Chromatography, Liquid , Microsomes, Liver/chemistry , ZebrafishABSTRACT
@#AIM:To observe the protective effect of pigment epithelium derived factor(PEDF)on retinal ganglion cells(RGCs)after acute injury of optic nerve in rats. <p>METHODS: Totally 60 healthy female SD rats were randomly divided into three groups: blank group, model group and experimental group, 20 rats in each group. Acute injury model of optic nerve in rats are established by crushing optic nerve. After the model of optic nerve injury was made successfully in model group, the rats were injected with balanced salt solution 5μL into vitreous cavity, and at 1 and 2wk later respectively they were injected again. In experimental group, after the model of optic nerve injury was made successfully, immediately the rats were injected with the PEDF 5μL into vitreous cavity, also at 1 and 2wk later respectively they were injected again. To observe the retinal morphologic changes and count the number of retinal ganglion cells, the specimen was given HE staining and observed under light microscope. The immunohistochemical semi quantitative method was used to detect the expression of Bcl-2 and Bax to observe the effect of PEDF on the optic nerve after injury. <p>RESULTS: Cell morphology of ganglion cells in experimental group was better and the number of RGCs was much more, comparing with the model group by HE staining. The expression of Bcl-2 and Bax in the experimental group was significantly different with that in the blank group and the model group(<i>P</i><0.05). The expression of Bcl-2 increased and the expression of Bax decreases in the experimental group compared with the model group. <p>CONCLUSION: PEDF can inhibit or weak the apoptosis of RGCs cells after optic nerve injury and alleviate the injury of optic nerve by increasing the expression of Bcl-2 protein or decreasing the expression of Bax protein.
ABSTRACT
AIM: To analyze the effect of pigment epithelium derived factor (PEDF) on nitrogen monoxide (NO) and expression of cysteine-containing, aspartate-specific proteases-3 (caspase-3) in retinal tissues of model rats with optic nerve crush injury.METHODS: A total of 60 SD rats were randomly divided into the blank control group, model group and PEDF group, with 20 rats in each group.Except the blank control group, the optic nerve crush injury rat models were established in the other groups, and left eyeballs were taken as samples.After successfully modeling, the model group were treated with intravitreal injection of 5μL of balanced salt solution while PEDF group were treated with intravitreal injection of 5μL of PEDF (0.2μg/μL).Two weeks later, the retinal tissues were collected, and changes of shape were observed under microscope after HE staining.The changes of NO level were measured by colorimetry assay, the expression of caspase-3 mRNA and caspase-3 protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western-blot.RESULTS: HE staining showed that retinal tissues of the blank control group arranged neatly and clearly.Retinal ganglion cells (RGCs) arranged in a monolayer, and cells were oval, uniform in size and distribution, the cell nuclei were clear, closely arranged, with clear boundaries.The retinal tissues of the model group were sparse in shape, RGCs showed vacuolar changes, the overall number of cells was reduced, and cell nuclei of residual RGCs showed pyknosis and uneven staining.RGCs in PEDF group were with slightly edema and arranged closely, and the degree of injury was significantly milder than that in the model group.Levels of Caspase-3 mRNA and protein and NO levels in the three groups showed the model group > PEDF group > blank control group (all P < 0.05).CONCLUSION: The application of PEDF can down regulate the expression of Caspase-3 and NO in rates with optic nerve injury and reduce RGCs injury.