Study On Neurotoxicity Of Dibulytin Dilaurate In Rats

Objective:As a kind of organic tin compound with active chemical property and mediocre noxious property, DBTD has already been used extensively as the stabilizer of PVC plastic products those are closely related with people's daily lives. Therefore it has attracked people's more attention.In order to study the effects of DBTD on neurotoxicity, we measured the rats'variation of the activities of SOD,GSH-PX and NOS and the contents of MDA and NO after subchronic exposure to poison. Then we observed the effects of DBTD on the apoptosis of brain cell and the injury state of DNA.Meanwhile,we examined the change in the fine structure of brain tissue under electronic microscope in search of forepart target of toxicity and discussed the possible mechanism of neurotoxic effect.Methods:Forty healthy male Wister rats with body weight of (190±10) g were provided by the Experimental Animal Center of Jilin University.The rats were randomly divided into four groups with three dose groups: control group,low dose group(5mg/kg), medium dose group(10mg/kg) and high dose group(20mg/kg). Each group included ten rats only. Control group was given corn oil byIntragastric administration. Dose group was given DBTD by intragastric administration.We exposed the rats to poison 7 weeks and 5 days one week. We measured their body weight before exposure to poison. After the last exposure to poison, we wait 48 hours then kill all the rats.We made the brain tissue into homogenate and measured the activity of SOD,GSH-PX and NOS and the contents of MDA and NO. We also detected the effects of DBTD on the cell cycle of brain cells and the injury state of DNA. Then we observed the change of ultrastructure of brain tissue under electron microscope.Results:1 Effects of DBTD on contents of SOD,GSH-PX and MDA in brain tissue :With the increased dose of DBTD, the activity of SOD and GSH-Px in brain tissue decreased, while the content of MDA increased gradually. The exposure groups of DBTD were obviously different compared with control group (P < 0.05) and each exposure group was also obviously disparate compared with each other (P < 0.05).2 Effect of DBTD on contents of NO and NOS in brain tissue : With the increased dose of DBTD, the content of NO in brain tissue increased. Exposure groups of DBTD were obviously different compared with control group (P < 0.05) and everyexposure group were obviously different among themselves(P < 0.05).The activity of NOS of high dose group was obviously high compared with control group (P < 0.05).3 Effect of DBTD on cell cycle and apoptosis of the brain cells in rats:The percentage of cells at G0/G1 phases evidently increased while the percentage of cells at S,G2+M phase decreased obviously with the increased dose of DBTD.The percentage of cells at G0/G1 phases of medium dose group and high dose group were significantly different compared with control group(P < 0.05) and every dose group were obviously different among themselves(P < 0.05).the percentage of cells at S phase of exposure groups of DBTD were obviously different compared with control group (P < 0.05) and every exposure group were obviously different among themselves(P < 0.05).the percentage of cells at G2+M phase of medium dose group and high dose group were significantly different compared with control group(P < 0.05) and every dose group were obviously different among themselves(P < 0.05). The apoptosis rate of brain cell of medium dose group and high dose group were apparently different compared with control group (P<0.05) and every exposure group is obviously different (P<0.05).With increased dose of DBTD,the apoptosis rate of brain cell tended to ascend.4 Effect of DBTD on DNA damage of brain cells in male rats: DNA damage of brain cells was observed with low dose ofSCGE.With dose increasing,DNA damage of brain cells aggravates gradually.The total injury rate of brain cells with high dose was 79.3%. Exposure groups of DBTD were obviously different compared with control group(P < 0.05) and every exposure group was obviously different among themselves (P < 0.05).5 Effect of DBTD on fine structure of the brain tissue DBTD of Low dose could alter the fine structure of brain tissue, and with dose increasing, fine structure of brain tissue changes obviously gradually,which proves that DBTD can permeate blood brain barrier and damage the nerve system.Conclusion:It shows that long-term exposure to DBTD could cause the activity of SOD and GSH-Px to decline but cause the content of MDA to increase.At the same time,it increased the content of NO and the activity of NOS in brain tissue . DBTD could change cell cycle progression and increase the apoptosis rate of brain cell. It could damage DNA. It alters as well the fine structure of the brain tissue.It concludes that DBTD could cause neurotoxicity in male rats.