| Objective:To explore the effect of GMDTC on the excretion of heavy metal cadmium and lead and its acute toxicity,and to provide data supports for the follow-up study on the treatment of heavy metal poisoning by GMDTC.Methods:1 Experiment of GMDTC capsule on the excretion cadmium by intragastricThe 40 SPF-grade male SD rats were randomly divided into blank control gro up（the animal number was 8）and cadmium model group（the animal number was32）,the cadmium model group was intraperitoneal injection CdCl2 3μmol/kg+β-ME60μmol/kg mixed solution,The blank control group was given saline in the same way.At the end of 12 weeks after modling,the cadmium model group rats were ra ndomly divided into model control group,GMDTC low,middle and high dose gro up,and respectively intragastric 0,100,200,400 mg/kg GMDTC enteric capsules,t he low and middle groups were given once a day,the high dose group was divide d into two times a day in the morning and afternoon,treatment for 5 days a wee k,2 weeks continuous administration.During the reseach time,detecting the 24h uri ne cadmium level,blood cadmium level and hematological indexes,at the end of th e experiment,the rats were dissected,and the main organ tissues were collected f or histopathological examination and the renal cadmium level was detected.2.Experiment of GMDTC on the excretion of lead by intraperitoneal injectionThe 48 SPF-grade male SD rats were randomly divided into blank control gro up（the animal number was 8）and lead model group（the animal number was 40）according to weight.The lead model group was intragastric 4g/L lead acetate soluti on for 30 days to build lead poisoning model,and the blank control group was int ragastric the ultrapure water at the same time.After the lead poisoning model was established,the lead model group rats were randomly divided into model control group,GMDTC low,meddle and high dose group and EDTA positive control gro up,intraperitoneal injection with 0,108.3,216.5,433.0 mg/kg GMDTC and 50 mg/kg EDTA,GMDTC was given for 30 consecutive days.During the reseach time,detecti ng the 24h urine lead level,blood lead level,trace elements in blood,serum biochem ical indexes and hematological indexes,at the end of the experiment,the rats were dissected,and the main organ tissues were collected for histopathological examin ation and the lead level in the tissues were detected.3 Experiment on acute toxicity of GMDTC by intravenous injection.SPF-grade SD rats and KM mice were all 20,half male and female,and were randomly divided into blank control group（n=10）and the GMDTC group（n=10）,half male and female.The GMDTC group of animals that were given GMDTC 2 times in 24h,and the interval was 8h,each animal was given maximum dose was 5 g/kg body weight and the maximum drug volume was 20 mL/kg.The blank control group was given equal volume of saline.After giving GMDTC,observe the animal’s toxic reaction and death every day,continuously observe for 14 days,weigh the weight of d0,d1,d3,d7 and d14,At the end of the experiment,the animals were dissected,and the main organs were observed by naked eye and weighed.Results:1 Experiment of GMDTC capsule on the excretion cadmium by intragastric.1.1 24h urinary cadmium levelDuring the treatment time,the 24h urinary cadmium level in the GMDTC middle and high dose groups were higher than that in the model control group（P<0.05 or P<0.01）;during the period of GMDTC withdrawal,the 24h urinary cadmium level in the GMDTC high dose group was higher than that in the model control group（P<0.05 or P<0.01）,and the 24h urinary cadmium level in the GMDTC high dose group was higher than that before treatment（P<0.05 or P<0.01）.1.2Cadmium level in bloodWhen the model was completed,the blood cadmium levels in the model control group and GMTDC treatment groups were significantly higher than that in the blank control group（P<0.01）.After the treatment,the blood cadmium level in the GMDTC treatment groups were not lower than that before treatment（P>0.05）.1.3 Correlation analysis between blood cadmium and 24h urine cadmiumBefore and after treatment,the correlation between blood cadmium and 24h urine cadmium in the GMDTC treatment groups were not statistically significant（P>0.05）.1.4 Renal cadmium levelCompared with the blank control group,the renal cadmium level in the model control group and GMDTC treatment groups were all increased significantly（P<0.01）.Compared with the model control group after the treatment,the renal cadm ium level in the GMDTC treatment groups were not decreased（P>0.05）.1.5 Haematological indexAfter the treatment,the RBC,HGB and HCT in the mdel control group were lower than that in the blank control group（P<0.05）.1.6 Pathological changes of organ tissues:Four rats in the model control group,three rats in the GMDTC low dose group and four rats in the GMDTC middle dose group showed different levels of the adhesion between the leaves of the liver and the necrosis of focal liver cells.In addition,in the model control group,a rat’s kidney was mainly inflammatory cell infiltration,in the GMDTC low dose group,a rat’s testis was mainly sperm cells shedding.2 Experiment of GMDTC on the excretion of lead by intraperitoneal injection.2.1 24h urinary lead levelDuring the treatment time,the 24h urinary lead level in the EDTA positive c ontrol group,GMDTC middle and high dose groups were significantly higher than that in the model control group（P<0.05 or P<0.01）and were all significantly hi gher than that before treatment in the same group.（P<0.05 or P<0.01）.2.2 Lead levels in biological tissuesWhen compared with the model control group,the brain lead level in the GMDTC middle and high dose groups were significantly lower（P<0.05 or P<0.01）,and the bone lead level in the GMDTC high dose group was significantly lower（P<0.05）;the liver lead level in the EDTA positive control group was significantly decreased（P<0.05）.But the kidney lead level and testis lead level in the treatment groups and model control group were not statistically significant（P>0.05）.2.3 Blood lead levelWhen the model was completed,the model control group,all the treatment groups of blood lead levels were significantly higher than that of blank control group（P<0.01）,and are more than 100μg/L,which suggest that the lead poisoning model was successful.After treatment,the blood lead level in the EDTA positive control group was lower than before treatment（P<0.05）,and the blood lead level in the GMDTC treatment groups was not decreased before treatment（P>0.05）.2.4Level of trace elements in bloodThere was no statistically significant difference between the treatment groups and the blank control group（P>0.05）.2.5 Pathological changes of organ tissuesTwo rats in the model control group,two rats in the EDTA positive control group,three rats in the GMDTC middle dose group showed myocardial fibrosis necrosis and inflammatory cell infiltration.Two rats in the model control group and two rats in the GMDTC low dose group showed liver cell necrosis and fibrous tissue.In the GMDTC low dose group,there were a case of splenic ischemic infarction,expansion of renal collecting tube and atrophy of testicular seminiferous tubule.3 Experiment on acute toxicity of GMDTC by intravenous injection.No animal death during the experiment,and normal weight growth in the GMDTC group was not statistically significant compared with the blank control group（P>0.05）.No obvious abnormality was found in the main organs of the animals.There was no significant difference in main organ coefficient between the GMDTC group and the blank control group（P>0.05）.Conclusions:1 GMDTC enteric capsules can increase the excretion of urine cadmium,suggesting that GMDTC intragastric can be effective,which has laid a theoretical foundation for the further development of the heavy metal cadmium drive in the export clothing.2 GMDTC injection can increase the excretion of urine lead and reduce the brain and bone lead level.3 The maximal tolerable dose（MTD）of GMDTC by intravenous injection is high than10g/kg body weight,its toxicity is small and its safety is high. |
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