Assessing The Effects Of Agents On The Cardiovascular Development And Neural Behavior Using Zebrafish Model

Objective The occurrence of adverse drug reactions(ADR)is on the rise year by year.ADR is mainly caused by chemicals and traditional Chinese medicines,which induce the skin,cardiovascular system and nerves injury.Founding and avoiding ADR can effectively protect human health.As an excellent traditional Chinese medicine,Dendrobium has been developed as a variety of products,but the reseaeches about its components are lacking.In this study,two kinds of extracts from Dendrobium,polysaccharides and erianin,were selected,and the effects on cardiovascular and neurobehavior were comprehensively evaluated by zebrafish model.At the same time,the side effects of a phenimidazole derivative were also investigated.The aim of this study was to provide theoretical reference for the rational use and risk avoiding of Dendrobium extract and anti-tumor agent.Methods(1)The acute toxicity of three agents was evaluated using zebrafish model,the survival,hatching and morphology of zebrafish was observed.(2)The effect of agents on the embryonic development was assessed through five aspects,including body length,yolk sac development,wound healing capacity,the development of eye and head.(3)The potential regulating effect of agents on the cardiovascular development was investigated under normal and pathological conditions.The heart beat,heart area,atrioventricular ratio,the distance between sinus venosus and bulbus arteriosus(SV-BA),and the interval of ventricular diastolic were choose as the assessment indicators of cardiac function.The sub-intestinal vein(SIVs)development was deemed as the indicator of angiogenesis development.(4)Three behavior methods,containing spontaneous movement,escape reaction and swimming behavior,were used to assess the effects of agents on the neural development.Results(1)Polysaccharide inhibited the hatching process,increased the yolk sac area,reduced the body length,and decreased the areas of eye and head.But the wound healing capacity was not influenced.Under the damaged condition of cardiovascular development,the application of polysaccharide was able to increase the heart area,disturb the regular atrio and ventricular beating,and prolong the interval of ventricular diastolic.However,polysaccharide can protect blood vessels through promoting damaged vessels development and inhibiting vessels injury.Polysaccharide increased the frequency of spontaneous movement and times of escape reaction,also made the swimming speed stable under light stimulation,without obvious influence under dark stimulation.(2)Erianin was able to delay the hatching process of zebrafish at several concentrations,increase the area of yolk sac and head,and reduce the body length.The wound healing capacity was not affected.Under the damaged condition of cardiovascular development,erianin protected the vessels through promoting damaged vessels development,and just influenced the regular atrio and ventricular beating.Conversely,when the normal cardiovascular development was subjected to the stimulation,erianin can inhibit the increase of SV-BA distance and the prolongation of interval of ventricular diastolic,but not ensure the normal development of SIVs.Erianin also increased the frequency of spontaneous movement and times of escape reaction,as well as made the swimming speed stable under light stimulation.(3)Phenanthroimidazole derivative obviously inhibited the proliferation of multiple tumor cell lines,also promoted the wound healing,inflammation process and ROS production.Meanwhile,the derivative facilitated the normal vessels development and regulated the heart beats,but decreased the escape time of zebrafish on stimulation.Conclusions(1)Polysaccharide accelerated the motor behaviors of zebrafish and inhibited the vessels damage.Because it aggravated the degree of damaged cardiac function,the polysaccharide should be used carefully on the organism with unhealthy cardiac function.(2)Erianin was also able to accelerate the motor behaviors of zebrafish and inhibit the vessels damage.The early application of erianin had the protective effects on the heart.(3)Phenanthroimidazole derivative exerted notable anti-tumor activity,as well as decreased the appearance of impaired wound healing and cardiovascular side effects.