Study On The Combined Effects Of Ketamine And Caffeine On Cytotoxicity

Psychoactive drugs refer to those drugs that can directly affect the central nervous system of the brain and make it excited or inhibited.Continuous use of psychoactive drugs will produce certain dependence and cause physical and mental damage to users.In today's world,the abuse of psychotropic substances has become a major international concern.In recent years,with the proliferation of international drugs and the rapid spread of new drugs,under such circumstances,the drug abuse model has changed from the original single drug abuse to the current multi-drug abuse model.Ketamine(KET)and caffeine(CF)are typical mixed-use psychotropic drugs,and the use of these two drugs may produce a more toxic effect.At present,most of the researches on ket and CF are focused on single toxicity,and most of them are on psychotoxicity,but there are few studies on liver toxicity.Therefore,in today's drug abuse,especially in the context of multi-drug abuse,it is of great significance to study the combined toxicity of KET and CF.This paper mainly explored the toxic effect of KET and CF on Hep G2 cells under single and combined effects,based on this,we deeply explore the effects of the apoptotic system and genotoxicity and explore the corresponding possible mechanisms.The MTT assay and the LDH activity experiment show that KET and CF individual have toxic effects on the Hep G2 cells,reduce cell survival rate,cause cell membrane damage,and show a certain dose-effect relationship.The combination of the two will cause stronger cytotoxicity,and the cell membrane damage will be more serious.The 0.5 + 1.0 m M group will show an additive effect when combined,and the other three groups will show a synergistic effect.The oxidative damage experiment(levels of ROS,contents of MDA,activities of SOD)showed that after KET and CF acted on Hep G2 cells alone,they would cause a certain degree of oxidative damage to Hep G2 cells,manifested by increased intracellular ROS level,increased contents of MDA,activities of SOD decreased andshowed a certain dose-effect relationship.The combination of the two will cause stronger oxidative damage,those showing a synergistic effect.The measured apoptosis rate and survival rate,as well as mitochondrial and Caspase-3 activity changes,the results showed that KET and CF single and combined action Hep G2 cells can induce apoptosis after 24 h,the cell mitochondrial membrane potential decreased Increased activity.This indicates that the two drugs impair the permeability of mitochondrial membranes and induce apoptosis through the mitochondrial pathway.The combined effect of KET and CF enhanced the ability to induce apoptosis,strengthened the decrease of cell mitochondrial membrane potential and enhanced the activity of Caspase-3,and enhanced the ability to induce apoptosis,which showed a synergistic effect.Comet assay show that both KET and CF can cause genotoxicity to cells.Under the separate action of KET and CF,with the increase of drug concentration,the tail DNA percentage,tail length and tail distance of Hep G2 cells also increase.Large,that is,DNA damage is enhanced,showing a dose-effect relationship.After the combined effect of KET and CF,the combined effect on tail DNA percentage,tail length and tail distance of Hep G2 cells showed a synergistic effect.The research in this paper shows that both KET and CF act on Hep G2 cells,which will produce obvious cytotoxicity,causing oxidative damage to the cells,inducing apoptosis and producing certain genotoxicity.The combined effect of KET and CF strengthens the ability of cytotoxicity,oxidative damage,apoptosis and genotoxicity,which shows a synergistic effect.