The Toxic Effects Of Neurobehavioral And Oxidative Damage Of Semicarbazide On Rats And Its Mechanism

Semicarbazide?SEM?is one of the metabolites of nitrofurans drugs,and it is also a decomposition product under high temperature conditions of plastic blowing agent azodicarbonamide.SEM had been found in animal derived and glass jar packaged food.European food safety authority warned to that the SEM of food could harm the human health at 2003.However,many countries do not regulate azodicarbonamide in food additives and packaging materials at present,China is one of them.This study elucidated the detriment of SEM by animal experiment,and hope to provide evidence for the understanding of SEM completely.44 male rats were randomly divided into four groups:Control group,SEM group:7.5,15,30 mg/?kg·bw?.The open field test?OFT?,elevated plus maze?EPM?and heliophobic test were used to observe the neurobehavioral and learning-memory toxicity,and discussed the toxicity mechanism through analysis the effect of monoamine neurotransmitters?MNTs?,gamma-aminobutyric acid?GABA?and N-methyl-d-aspartic acid receptor?NMDAR?in rats exposed to SEM.On the other hand,this study research the metabolism and injury toxicity through oxidative damage items,hepatic metabolic enzymes and residue situation of SEM.SPSS18.0 was used for the statistical analysis,and the main results are showed as follows:?1?The general toxicity of SEM on rats:The weight increase of rat and the food utilization rates were significantly lower in the high-dose SEM group compared with the control group?P<0.05 or P<0.01?.The kidney coefficient of rat was significantly higher in the medium-dose SEM group and high-dose SEM group compared with the control group?P<0.01?,and the testicular coefficient of rat was significantly higher in the high-dose SEM group compared with the control group?P<0.05?.?2?The neurobehavioral toxicity of SEM on rats:No significant differences were found in the OFT,EPM and heliophobic test among the groups before SEM exposure?P>0.05?.After SEM exposure,the total distance traveled was significantly lower in the medium-dose SEM group and high-dose SEM group compared with the control group?P<0.05?.The distance traveled in the center was significantly lower in the high-dose SEM group compared with the control group?P<0.05?.The total distance traveled was significantly lower in the high-dose SEM group than in the control group?P<0.05?.The closed arm time percentage?CT%?was significantly higher in the SEM groups than in the control group?P<0.05?.The open arm time?OT?,open arm time percentage?OT%?,open arm entries?OE?,open arm entries percentage?OE%?were significantly in the SEM groups lower than in the control group?P<0.05 or P<0.01?.In the learning phase of heliophobic test,the latent period was significantly shorter in the medium-dose SEM group and high-dose SEM group compared with the control group?P<0.05 or P<0.01?,and the error frequency was significantly higher in the high-dose SEM group compared with the control group?P<0.05 or P<0.01?.In the retesting phase of heliophobic test,the latent period was significantly shorter in the high-dose SEM group compared with the control group?P<0.01?,meanwhile,the error frequency was significantly higher in the high-dose SEM group compared with the control group?P<0.05?.?3?The effect of neurotransmitters in rats'brain exposed to SEM:The concentration of GABA in the hippocampus was significantly lower in the high-dose SEM group compared with the control group?P<0.05?.The concentration of GLU in the hippocampus was significantly higher in the medium-dose SEM group and high-dose SEM group compared with the control group?P<0.05?.The hypothalamus concentration of 5-hydroxytryptamine?5-HT?was significantly higher in the high-dose SEM group compared with the control group?P<0.05?.The frontal cortex concentration of 5-HT was significantly higher in each dose group compared with the control group?P<0.05 or P<0.01?.The concentrations of norepinephrine?NE?in the hypothalamus and frontal cortex were significantly higher in the high-dose SEM group compared with the control group?P<0.05 or P<0.01?.The hypothalamus concentration of dopamine?DA?was significantly higher in each dose group compared with the control group?P<0.05 or P<0.01?.The frontal cortex concentration of DA was significantly higher in the high-dose SEM group compared with the control group?P<0.01?.The frontal cortex concentration of NMDAR was significantly higher in the medium-dose SEM group and high-dose SEM group compared with the control group?P<0.05?.The hypothalamus activity of monoamine oxidase?MAO?was significantly lower in the medium-dose SEM group and high-dose SEM group compared with the control group?P<0.05?.The frontal cortex activity of MAO was significantly lower in each dose group compared with the control group?P<0.05 or P<0.01?.?4?The oxidation damage of rats exposed to SEM:The concentration of reactive oxygen species?ROS?in the serum was significantly higher in the medium-dose SEM group and high-dose SEM group compared with the control group?P<0.01?.The concentration of 8-iso-prostaglandin F_2?(8-iso-PGF_2?)in the liver homogenate was significantly higher in the high-dose SEM group compared with the control group?P<0.01?.The liver activity of cytochrome P450?CYP450?was significantly lower in each dose group compared with the control group?P<0.05 or P<0.01?.The liver activity of UDP-glucuronosyltransferase?UGT?and glutathione S-transferase pi?GSTpi?were significantly lower in the medium-dose SEM group and high-dose SEM group compared with the control group?P<0.05?.The level of SEM in serum elevated significantly in each dose groups compared with control group?P<0.01?.The content of SEM in urine was no obvious difference between three poisoned groups,The above results indicated that SEM has many aspects of toxicity.The ways of SEM-induced anxiety and learning-memory impairment might be its effect on MNTs,GABA and NMDAR in brain.Meanwhile,SEM may cause the oxidative damage of rat,inhibit the hepatic metabolic enzymes and affect the normal physiological functions.