Protection Of Rution Against Learning And Memory Dysfuntion Caused By Tmt And The Relationship With Monoamine Neurotransmitters And Their Metabolites

Objective: Trimethyltin (TMT) is a highly toxic chlorinated productduring the production of organotin stabilizer produced, and widely usedinsecticides, paints, rubber, and PVC plastics production. At present theTMT acute poisoning incidents continue to be reported and the harm wasincalculable. Studies have shown that TMT toxicity main damage to thecentral nervous system and the learning and memory function is animportant part to evaluate whether the central nervous system damaged.Domestic and foreign some research on the TMT specific toxic effects, butthe specific mechanism of toxicity inconclusive. This study was to use thedetermine TMT exposure dose to established the model of BALB/c mouseacute poisoning, to study the impact on learning and memory as well as thechange of monoamine neurotransmitters in mice by TMT acute exposure,aim to explore the possible mechanisms of TMT poisoning and relevanceof learning and memory dysfunction and monoamine neurotransmitterscaused by TMT.Method:①The SPF male adult8weeks old BALB/c rats were randomly divided into control group and the TMT-exposed group, theTMT-exposed group was divided into five different dose2.00mg/kg,2.25mg/kg,2.50mg/kg,2.75mg/kg and3.00mg/kg, with6mice in eachgroup. The rats of TMT-exposed group were intraperitoneal injection byTMT and the control group rats were intraperitoneal injection of normalsaline, then observing the behavior of mice and by the Morris water mazeto calculation the escape latency to determine the TMT acute exposure dosein this experiment.②High performance liquid chromatography-electrochemical method (HPLC-ECD) detected the seven monoamineneurotransmitters (E, NE, DA, DOPAC, HAV,5-HT,5-HIAA) levels incortex and hippocampus of TMT-induced BALB/c mice.③According tothe result of①, the male BALB/c rats were randomly divided into fourgroups respect control group, TMT-induced group, Rutin group and TMTvs. Rutin groups, with6rats in each group. The Rutin group rats wereintraperitoneal injection Rutin a week, TMT exposed mice were givensaline for former six days and the seventh day of injection TMT, TMT+Rutin group rats were treatment Rutin six days and last day intraperitonealinjection TMT, control group rats were given equal quantity saline a week.After the TMT exposed24hours, observe the performance of mice in eachgroup and did the water maze experiment to record the escape latency.④detected the level of seven monoamine neurotransmitters in hippocampusand cortex of each group rats. It was to discussion the change of rats’ behavior and the effect on monoamine neurotransmitters after Rutinpretreatment.Results:①After24hours of TMT-induced by intraperitoneal injection,the behavior of rats in control group and low-dose TMT group (2.0mg/kg,2.25mg/kg) were normal, the rats of2.50mg/kg and2.75mg/kg TMTexposure dose had the phenomenon of tremors and eating and drinkingwere reduced and had some slapstick traces, the rats in the3.00mg/kg TMTexposed has the extremely abnormal, reduced activity and significanttremor and tail bites. The results of Morris water maze had shown that withthe training number increase the time of the rats which in control group and2.00mg/kg TMT-induced find the hidden platform that escape latency wereshorter, but there was no significant difference between the two groups(P>0.05). The escape latency of fourth trained of2.25mg/kg TMT exposedrats were significantly increased compared with control group (P<0.05).The mice of2.50mg/kg TMT exposed and2.27mg/kg TMT exposed groupsfrom the third training, that escape latency were significantly longercompared with the control group (P<0.05), but between the two times wasnot significantly difference (P>0.05). Because of3.00mg/kgTMT exposedmice completely lost the ability to swim, so no data of Morris water maze.②The monoamine neurotransmitter levels of mouse hippocampus andcortex had changed in different time points of TMT exposed. Comparedwith control group the NE level in hippocampus increased before1hour and then decreased to normal, the level of DA has significant decline afterTMT exposed0.5h (P<0.05), The levels of DOPAC and HAV weresignificantly increased from TMT exposed3hour(P<0.05), The5-HT and5-HIAA levels were reduced after exposure0.5hour (P <0.05) and nosignificant change of E. Each monoamine neurotransmitters in mousecortex compared with the control group: the NE level was elevated afterexposure1h (P<0.05), the content of E has decreased after12h, DA levelhas lower after3h,5-HT and5-HIAA levels were reducing from0.5h, andthe DOPAC and HAV levels have no significantly changed in each time.③The rats were given Rutin then did the Morris water maze test, theescape latency of rats except TMT exposed group were significantlyreduced. The escape latency of rats in TMT exposed group wassignificantly longer than control group from fourth training. The escapelatency of rats in Rutin+TMT group was significantly shorter comparedwith control from fifth training. The escape latency of rats in Rutin groupwas shorter than other group and from third training has significantlyreduced compared with TMT group. The escape latency of mice in Rutingroup were shortened compared to the control group rats with the sameperiod but has no significant difference.④The content of monoamine neurotransmitter in mice hippocampuscompared to the control group after TMT exposure24h: NE level had nosignificant change, HAV level elevated and other monoamine neurotransmitters were lower (P<0.05). The content of monoamineneurotransmitter in mice cortex compared with control: E, DA, DOPAC,5-HT,5-HIAA levels was declining and NE and HAV content had nosignificant change. The monoamine neurotransmitters of cortex in Rutingroup rats has no significant changes compared with control, but in thehippocampus the NE, DA and DOPAC levels were rose than control,contrary the5-HT,5-HIAA levels were decreased and the E and HAV levelhave no significant difference. The rats of rutin pretreatment one week andTMT exposed24hours compared to control that the DA, DOPAC,5-HT,and5-HIAA levels in hippocampus were increased by different degrees,but HAV level was reduced and the content of NE and E have nosignificant changes, that in cortex the NE, DA,5-HT and5-HIAA levelswere increase and the E, DOPAC and HAV content have no changesignificantly.Conclusion:①Determine the TMT acute exposure dose is2.25mg/kg,and after exposure24hours it can lead to BALB/c mice learning andmemory dysfunction.②After TMT acute exposed, in hippocampus andcortex the E level has not significantly changed, but the NE level has riseand the levels of DA, DOPAC, HAV,5-HT, and5-HIAA have declined.③Rutin pretreatment a week after TMT-induced24hours, the escape latencyhas no significantly prolonged that suggested the Rutin have a protectiveeffect on learning and memory function by TMT.④Under the same experimental conditions, in hippocampus and cortex the E level has nosignificantly change and the DA,5-HT,5-HIAA levels have rise andantagonize the NE and HAV levels raised by Rutin pretreatment. Theresults suggest that the protective effect of Rutin on learning and memorydysfunction caused by TMT may be associated with the concentration ofmonoamine neurotransmitters changes.