The Effect Of Environmental Lead And Cadmium Exposure On Urinary Metallothionein Excretion In A Chinese Population

Objective: Metallothionein(MT)is a low molecular weight(6~10 kD)protein rich in cysteine(~30%)and capable of binding with various divalent metals such as cadmium(Cd)and lead(Pb).Induced by stress factors including metals,MT is primarily synthesized in liver and is delivered to kidney through the circulation.Due to its low molecular weight,MT easily passes through the glomerular filter and is reabsorbed in the proximal convoluted tubules(PCTs).Thus normally only a small amount of MT is detected in urine.The urinary MT(UMT)excretion increased while PCTs are injured and renal tubular dysfunction occurred.Both Cd and Pb have nephrotoxicity,but most of the previous studies have been limited to the effects of cadmium or lead as a single factor on renal function.Since environmental hazards rarely act on the human in a single element,we investigated the effects of coexposure of Cd and Pb on UMT excretion among the residents neighboring a closed lead smelter and used UMT as a biomarker of early effect to explore the BMD of cadmium and lead in order to explore the possibility of UMT worked as the biomarker for Cd and Pb exposure and nephrotoxicity.Methods: A village near the lead smelter that was closed 10 year ago in south-central China,was selected as a cadmium-lead-polluted area,and 167 of local residents(110 females and 57 males)were recruited in the study.Another village with no obvious pollution sourse,where is 40 kilometers away from the polluted area was selected as the control area,and 169 of local residents(female 108,male 61)were recruited.The basic information of the subjects is obtained by using a questionnaire and biological samples incuding blood and urine were collected.Patients with diseases such as in liver and kidney were excluded.Determination of urinary Cd(UCd)and urinary Pb(UPb)by using graphite furnace atomic absorption spectrometry(GF-AAS).UMT,urinary Nacetyl-?-D-glucosaminidase(UNAG)and urinary albumin(UALB)were measured by enzyme-linked immunosorbent assay(ELISA).Urinary creatinine(Cr)was determined by using Jaffe's method.All of the above urinary parameters were calibrated by creatinine.Quantitative data were descrided with the geometric mean and its 95% confidence limit.One-way analysis of variance was used to compare the basic situation of the exposed group with the control group,to evaluate the effect of Cd or Pb exposure on UMT,UNAG,and UALB,Pearson correlation coefficient was employed to analyze the correlation between UCd,UPb and UMT,UNAG or UALB.Standardized regression analysis between UCb and UPb and UMT,UNAG or UALB was performed using linear regression models.By using the 95% value of UMT,UNAG and UALB in the control population as cut points,the prevalences(the ratio of the number of subjects exceeding the cut point to the number of observed group)in different levels of UCd and UPb were used as the benchmark response(BMR)to calculate the bechmark dose(BMD)and the BMD lower bound(BMDL)of UCd and UPb using the software BMDS 3.0 issued by the US Environmental Protection Agency(EPA).Results: UCd was positively correlated with UPb in both control and exposed groups(r=0.410,P<0.01).The levels of UCd,UPb,UMT,UNAG,and UALB in the exposed population were significantly higher than those in the control(P<0.01),and UMT was positively correlated with UCd,UPb,UNAG,and UALB,respectively.The standardized regression coefficients of UMT with UCd and UPb were 0.184 and 0.544,respectively.And the standardized regression coefficients of UNAG with UCd and UPb were 0.442 and 0.180,respectively.These data suggest that UPb has a greater impact on UMT excretion compared with UCd.The BMDs of UCd and UPb for UMT were 1.22 ?g/g Cr and 6.98 ?g/g Cr,respectively,which was lower than that for UNAG(2.17 ?g/g Cr and 10.47 ?g/g Cr for UCd and UPb,respectively).The BMDs for UMT combined with UANG and/or UALB were even lower,as low as 0.6~0.8 ?g/g Cr and 5.38 ?g/g Cr for UCd and UPb,respectively.In the group with low level of UPb(below BMDL),Cd exposure presented little effect on UMT excretion,while in the group with low level of UCd(below BMDL),UPb showed an signifficantly effect on UMT excretion,and UMT excretion further increased with the elevation of both UCd and UPb levels.Conclusion: UMT is more sensitive than UNAG for reflecting Cd and Pb exposure and nephrotoxicity.Cd and Pb present a synergistic effect in nephrotoxicity of PCT injury.Compared with Cd exposure,Pb exposure appears to diplay a more evident effect on UMT excretion.