Research On The Therapeutic Dose And Time Of GMDTC Treated(iv) Rabbits Model Induced By Cadmium

Objective:To investigate the effect on different dosage and treatment time of GMDTC on cadmium poisoning rabbits model,and to find the best therapeutic dose.Methods:1.Animal grouping and processing: 85 male New Zealand rabbits were randomly divided into control group（which injecting saline through ear vein with ten）and model group[which injecting CdCl₂（2 mol/kg）and ME（40 mol/kg）mixed solution through ear vein with seventy-five],5 m L/kg body weight,once a day for five days.On the forty-one day of the experiment,the blank group were randomly divided into control group and GMDTC high dose control group（108 mg/kg）,five rabbits in each group,model group were randomly divided into model control group,EDTA control group and GMDTC low dose（12 mg/kg）,middle dose（36 mg/kg）and high dose group（108 mg/kg）,each group was divided into one week,two weeks and four weeks,five rabbits in each group.The blank group and the model control group were injected 0.9% Sodium Chloride via ear vein intravenous for 250 m L,the EDTA control group were given 93.5 mg/kg EDTA solution according to body weight into 0.9% Sodium Chloride which is 250 m L in the same way,the GMDTC high dose control group,the GMDTC low,medium and high dose groups were given 108,12,36,108 mg/kg GMDTC solution respectively,according to body weight into 0.9% Sodium Chloride which is 250 m L through ear vein intravenous,30-35 drops per hour,once a day,six times a week.2.Sample collecting and detecting: 2 m L urine was collected for 3 consecutive days before giving GMDTC,the urine was collected for creatinine and β₂-MG.Each collecting time is divided into two sections,the first paragraph is starting intravenous to six hours,and the second paragraph is six hours to the next day of 24 hours,which for detecting the dynamic urinary cadmium.Collecting anticoagulant and nonanticoagulant blood through ear artery on one day before GMDTC intravenous and dissection,which is used for deceting blood cadmium and blood biochemical.The experimental animal were sacrificed on the 48 th day,55 th day and 68 th day through anaesthesia respectively,the digesting juice of liver,kidney and testis for deceting Cd²⁺ and trace elements,the digesting juice of femur for testing bone Cd²⁺ and bone Ca²⁺,then do the pathological examination of liver,kidney and testis.Results:1.Urine β₂-MG.After the completion of the rabbit cadmium poisoning model,urine β₂-MG in the model control group and treatment group is higher than the control group for three consecutive days（P<0.05）.2.Urinary cadmium2.1 0⁶ hour of urinary cadmium after intravenous.Compared with the model group at the same point,the 0⁶ hour urinary cadmium of New Zealand rabbits are increased in each EDTA control group and in the middle and high dose group on the first treatment day（P<0.05 or P<0.01）.Compared with the first day of treatment in the same group,the 0⁶h urinary cadmium on these days（13,15,20,22,27）is reduced（P<0.05）.On the first day of treatment,the EDTA control group,GMDTC low dose group,middle dose group and high dose group,the urinary cadmium was 6¹2 times,2⁵ times,8¹6 times and 60¹26 times than of the model group.2.2 7²4 hour of urinary cadmium after intravenous.Compared with the first day of treatment in the same group,the the 7²4h urinary cadmium on these days（15,20,22,27）is reduced（P<0.05）.On the first day of treatment,urinary cadmium in these groups（EDTA control group,GMDTC low,middle and high dose group）is 9³0 times,2⁵ times,5⁷ times and 66¹02 times than of the model group respectively.3.Blood cadmium.Compared with themodel group at the same point,blood cadmium are significantly lower in these groups（EDTA control group,GMDTC low,middle and high dose group）of four weeks treatment（P<0.01）.Compared with the same group before intravenous,blood cadmium are significantly lower in model group and each treatment group（P<0.05）,but there is a significant difference decline rate of cadmium in each group.The elimination rate of blood cadmium in these groups（model control group,EDTA control group and GMDTC low,middle and high dose group）of four weeks is 34.49%,84.37%,77.92%,85.34% and 86.10% respectively.4.Renal cadmium.Compared with the model control group in the same point,GMDTC middle and high dose of one week,two weeks and four weeks of renal cadmium is reduced（P<0.01）,but the renal cadmium is increased in EDTA control group of one and two weeks.And the elimination rate of renal cadmium is 1.29%,14.25%,27.96% and 61.24% on EDTA control group,GMDTC low,medium and high dose group respectively.5.Visceral cadmium.Liver cadmium,testicular cadmium,and femur cadmium is higher comparing to the blank group in the model group,EDTA control group and GMDTC treatment group（P<0.01）.6.Trace elements in blood and viscera.6.1 Trace elements in blood and liver.At the end of intravenous,there is no difference between the treatment group and the blank group（P>0.05）.6.2 Renal trace elements.Compared with the blank group,the levels of renal Fe²⁺ in the model control group,EDTA control group and GMDTC group were higher than those in the control group（P<0.05）.6.3 Testicular trace elements.Compared with the blank group,the levels of testicular Ca²⁺ is decreased in the EDTA two week group,GMDTC low and middle group of one week,two weeks group and the high dose group（P<0.05 or P<0.01）.Compared with the blank group,the testicular Zn²⁺ in the model group,EDTA control group,GMDTC low,two weeks group and high dose of one week group are all lower than the control group（P<0.05 or P<0.01）.7.Femur detection.There is no significant difference between treatment group and blank group in bone mineral density,bone calcium and bone biomechanics（P>0.05）.8.Pathological examination results8.1 Liver.There is liver damage in model group and also treatment group.The mainly damage are water denaturation and inflammatory cell infiltration.Liver lesions is 100 pecent in model group of 4 weeks.The proportion of liver lesions in treatment groups is smaller than the model group.8.2 Kidney.There is renal damage in model group and also treatment group.The mainly damage are interstitial nephritis,pyelonephritis,vacuolar degeneration and cell tubular type.There is a high proportion of renal disease in model group.And there is a similar proportion of renal damage in EDTA control group and model group.No pathological changes is found in GMDTC high dose two weeks group,the proporation of renal lesions in the treatment groups is smaller than model group.8.3 Testis.There is testicular damage in in model group and also treatment group.The mainly damage are atrophy of seminiferous tubulesand multinucleated macrophages.There is no significant difference between treatment group and blank group about testicular damage.Conclusion:1.The urinary cadmium of GMDTC at the dose of 108 mg/kg was 100 times higher than the model group,and 9¹0 times higher than the EDTA treatment.The results showed that GMDTC can significantly promote the excretion of cadmium through urine.2.The elimination rate of renal cadmium are 52.12% and 61.24% of GMDTC at the dose of 108 mg/kg in two weeks and four weeks respectively.The results suggest that GMDTC can significantly remove cadmium in renal cells.3.When the rabbit dosage of GMDTC is 108 mg/kg,it is equivalent to human dosage of 36 mg/kg as well as 1.8 g everyday.GMDTC had no effect on animal organ coefficient and has low effects on metal trace elements.GMDTC can alleviate liver and kidney toxicity caused by cadmium.GMDTC has little side effect and meet the basic requirements of medicine.