Changes Of Enzyme Activity In Oxidative Stress Iuduced By Methamphetamine In Striatum Of Rat Brain

BACKGROUNDMethamphetamine(METH) is one of the amphetamine-type stimulant.It is often called ice because it's crystals clear resemble ice.METH has multiple pharmalogical and toxicological effects.Recent reports revealed that brain was the main target of METH-toxicity.METH can cause severe neurological injury which include dopamine(DA) depletion,dopaminergic nerve terminals degeneration,decreasing of the activity of tyrosine hydroxylase and number of DA uptake sites,as well as neuron apoptosis,are simillar to that of neurodegenerative disorders such as Alzimer's disease and Parkinson's disease.METH-induced neurotoxicity is a complex process,which may include oxidative stress,neurotoxicity induced by glutamate,mitochondrial dyfunction and activation of apoptosis pathways.Yet the exact mechanism was still unknown.OBJECTIVEMany researches found oxidative stress was an important mechanism of METH neurotoxicity.METH induced the production of a lot reactive oxygen species(ROS) and reactive nitrogen species(RNS),which damaged central nervous system.Animal models were used to survey the neurotoxicity of METH by histopathological and neurochemical methods.On the basis of these results,to observe the oxidative stress induced by METH by detecting the total nitric oxide synthase(NOS)activity, inducible nitric oxide synthase(iNOS)activity,structure of nitric oxide synthase(cNOS) activity,the glutathione peroxidase(GSH-PX)activity,the content of reduced glutathione(GSH) and the chymotryptic activity.METHODS1.Animal protocol and toxicity observationWistar rats,weighting from 180g to 220g(the experimental animal centre of Southern Medical University,China) were randomely divided into group(A)(n=18) and group(B)(n=18).The METH was dissolved in saline.Group B were received i.p. injections of METH(15mg/kg×8,at 12h intervals),and Group A was injected with saline.The body weight and behavioral changes of rats were recorded.The histological changes of brain,liver,spleen,lung and kindy were observed by HE stain.Detect the change in cells by TUNEL,the content of TH by westernbloting.Imunohistochemical detection of OX-42 was used to evaluate the change of microglias.2.Changes of enezyme activity induced by METH in striatum of rat brainTo detect material changes by using nitric oxide synthase(NOS) test box, glutathione-peroxidase(GSH-PX) test box and glutathione(GSH) test box and chymotrypsin-like activity using Suc-Leu-Glu-Val-Tyr-AMC.RESULT1.The body weight of rats decreased(P=0.000).Rats showed obvious behavior changes,such as moving heads constantly and easy to be irritated.Apoptosis of cells increased significantly(P=0.000).The content of TH decreased.OX-42-positive microglias incrsesed significantly(P=0.000) and were activated.Microglias kept in a quiescent condition.They had small cells some and long processes.When microglias were activated,their somas became bigger and processes became shoter and wider and they looked like "bushy"and "amoeboid".2.NOS activity increased significantly(P=0.000).iNOS(P=0.000) and cNOS(P=0.007)activity also increased significantly.The content of GSH decreased obviously(P=0.000).GSH-PX activity didn't change(P=0.097).Chymotryptic activity also increased(P=0.015).CONCLUSION1.METH can cause obvious neurotoxicity,which included behavior changes of rats,inducing obvious apoptosis of cells,decreasing the content of TH and making microglias activate.METH also has toxic effects on liver and lung.2.METH made oxidation and antioxidant capacity change in striatum of rat brain.METH increased the total NOS activity,iNOS activity,cNOS and chymotryptic activity,decreased the content of GSH.So oxidative stress induced by METH administration play an important role in METH neurotoxicity.