The Research On Safety Of SeNPs And The Mechanism Of Protecting Intestinal Side Effects Of NDP In Mice

Chemotherapy as an effective therapies method is commonly used to treat various cancers.The high incidences of toxic and side effects have restricted the full use of its anti-cancer efficacy.The incidence of diarrhea,which is a typical of gastrointestinal toxic side effects,greatly affects the course of treatment,resulting in the changes of treatment program,reducing the dose,extending the treatment cycle and even stopping the treatment.However,it is very regrettable that the current research on diarrhea caused by chemotherapy only stays at the pathological level,the intrinsic molecular mechanism being unintelligible has created many obstacles to the in-depth study It is an important problem badly in need of solution in in-depth understanding of the molecular level of chemotherapy induced diarrhea mechanisms,finding the drugs with non-toxic side effects and lack of interruption to the treatment to prevent diarrhea.Nedaplatin is the second-generation platinum drug invented by Japan after Cisplatin.Compared with cisplatin,it is more effective against certain cancers and has lower side effects.However,the lack of the studies about the mechanism of toxicity of nedaplatin basing on the clinical and animal models led to the inability of nedaplatin to be used worldwide.In this experiment,animal models being used to evaluate the toxic effects of nedaplatin,the toxicity of nedaplatin on mouse models was mainly manifested as severe loss of body weight and diarrhea,and the incidence of diarrhea in particular was maintained at 80% in previous experiments.At the same time,after the combination of nano-selenium,it was found that both the loss of weight and the incidence of diarrhea were significantly improved.Therefore,we speculated that the nedaplatin animal model may be an animal model that molds chemotherapy to cause diarrhea.Based on the nedaplatin diarrhea model and the obvious protective effect of nano-selenium,the molecular mechanism of chemotherapy-induced diarrhea was studied.At the same time,the protective effect of nano-selenium chemotherapy was evaluated and the mechanism was studied.Based on the nedaplatin diarrhea model,we found that the occurrence of diarrhea was highly correlated with the upregulation of genes and proteins related to p53/TSP-1 in the small intestine and showed a certain time effect.At the same time,the upregulation of p53/TSP-1 may be related to the distribution of p53 nucleoplasm and protein Trx1-TrxR1 with the regulation of intranuclear oxidation.When combined with nano-selenium,the toxicity caused by nedaplatin was significantly improved and diarrhea didn't occurred.Further more,the intestinal cells showed a normal tendency.The p53/TSP-1 gene up-regulated by nedaplatin was detected by detecting relevant genes and proteins in the small intestine.Both proteins and proteins were significantly down-regulated after nano-selenium was added.This indicates that nano-selenium may play a role in p53/TSP-1 inhibitors,and it can achieve chemotherapy protection through dual inhibition of p53/TSP-1.The effect of nano-selenium is surprising,and whether it affects the efficacy and self-safety of nedaplatin is also worth studying.Based on animal solid tumor models,we studied the effect of nano-selenium on nedaplatin efficacy and toxicity on tumor models.It was found that nano-selenium had no effect on the therapeutic efficacy of nedaplatin on tumor inhibition,but it could significantly improve the loss of body weight caused by nedaplatin toxicity.Based on normal mice,it was found that nano-selenium inhibited the reversible inhibition of p53/TSP-1 related genes in the small intestine.In addition,liver,kidney,and blood toxicity tests on mice revealed that nano-selenium itself was low-toxic and safety was very high.Therefore,we can speculate that the underlying molecular mechanism of chemotherapy-induced diarrhea may be highly correlated with the upregulation of p53/TSP-1 related genes and proteins in the small intestine.Nano-selenium acts as a dual inhibitor of p53/TSP-1,and it inhibits the up-regulation of related genes and proteins to achieve chemotherapy protection.What is more valuable is that nano-selenium has high safety and no effect on the anti-cancer efficacy of nedaplatin,and has a high degree of selective protection.