GRH, A Novel Homospermidine Conjugate In Vivo Distribution And Relation With Polyamine Research

Experimental purposes:Polyamine content in abnormal growths of tissue cells is much higher than other normal tissue cells,and natural polyamine as carrying groups with strong carrying capacity. Many data demonstrated that manyanthraquinone agents exert potent anti-cancer activity. Furthermore, anthraquinone-polyamine conjugatealso could be recognizes by polyamine transporter of tumor cells and transported into tumor cells, and thenexert targeting antitumor effects. This HPLC method is used to study the GRH, a novelanthraquinone-polyamine conjugated, in the body distribution, influence of polyamine metabolism and oralabsorption characteristics.Experimental method:The body distribution and the influence of polyamine metabolism of GRH were detected by HPLCmethod in a normal kunming mice and optimization of liver injury in mice. Furthermore, the oralabsorption characteristics of GRH was evaluated in Caco-2cells model in vitro.The result:HPLC method for determining the absorption peak area of GRH and polyamine, through standardcurve to calculate the GRH and polyamine, according to the results of the content of the caudal vein afterdosing, GRH can be rapidly distributed in liver, spleen, lung and the kidney four organs, because it can notthrough the blood brain barrier and not in the distribution of brain through comparing normal group andliver damage, which can determine the liver is the main metabolic organs, as its major excretory kidney, thespleen is the main storage organs and lungs for some of its metabolic organs. GRH the tendency of thequantity in each viscera and tumor signal SPM, SPD, PUT the change trend of consistent, showed the GRHto polyamine can produce the amount of influence, so the GRH can play the role of anti-tumor.Optimization through Caco-2cells model experiment, found the GRH can be absorbed in the smallintestine and its effective oral, and oral absorption process with dose and time dependent, at the same timeGRH affect the quantity of polyamine can, again proved the GRH antitumor effect.Conclusion:GRH can be oral absorption, dose and time dependent, intravenous tissue distribution speed after the treatment, the liver metabolism, renal excretion, the amount of change trend and the change trend ofpolyamine content is consistent, can affect the amount of polyamine, have certain anti-tumor effect.