The Effect Of Metallothionein Antibody On Renal Dysfunction In The Population Environmentally Exposed To Cadmium

Cadmium,an environmental pollutant,causes a number of adverse health effects.Kidney damage is the critical effect of long-term and low-level cadmium exposure.Metallothionein(MT) is a family of stress proteins containing a high content of cysteine and divalent metals.MT expression could be induced by many factors,especially by metals,i.e.cadmium,zinc,copper,etc.It has been demonstrated that MT plays an important role in the transportation,detoxication,and excretion of metals in some studies related to several toxic metals,especially for cadmium.It also has been reported that anti-metallothionein antibody(MT-Ab) is present in the circulation of human body.Chen,of our research group,found that subjects with higher MT-Ab levels more readily develop cadmium induced renal dysfunction under similar occupational cadmium exposure.However,its mechanism is unclear.The relation between MT-Ab level and renal dysfunction induced by environmental cadmium exposure has not been shown either.To explore if the difference of MT-Ab forms influences the measurement of MT-Ab and to observe the mechanism of metallothionein antibody(MT-Ab) affecting cadmium induced renal dysfunction,we did the methodological research. We divide plasma samples into with and without MT pretreatment groups,and then run the MT-Ab measurement.No statistic significance was found in the difference of value of optical density(OD) between the two groups in both human and rat plasma. We explored the competitive combination to MT between MT-Ab and ion of cadmium and zinc.Every group contains 0,5,10,20,40 mg/mL 5 different dose subgroups.Competitive enzyme linked immuno-sorbent assay(ELISA) is adopted. The extent of competitive combination is determined by optical density(490nm). The concentration of coating MT is 1μg/mL,concentration of MT-Ab is 32U.The optical density decreases following the increase of concentration of cadmium or zinc. There is obvious competitive combination between MT-Ab and ion of cadmium and zinc.MT-Ab can dissociate CdMT into free Cd ion,which is one of the factors to induce kidney damage.The aim of this study was to investigate whether cadmium-induced renal dysfunction is related to the presence of the plasma MT-Ab in residents environmentally exposed to cadmium.Plasma metallothionein antibody was determined by enzyme linked immuno-sorbent assay(ELISA) techniques,and both exposure assessment and risk assessment were conducted in cadmium exposed residents in China.We demonstrate that there is a significantly increased prevalence of renal dysfunction with respect to the level of urinary cadmium in a dose-dependant manner.We found no significant correlations between the levels of MT-Ab and the external or internal doses of cadmium(P＞0.05),but the levels of MTOAb did correlate positively with two biomarkers of renal dysfunction,i.e. N-acetyl-β-D-glucosaminidase(UNAG;r=0.125,P＜0.05) and urinary ^-microglobulin(UB2M;r=0.234,P<0.05).We found that kidney function recovered group has a lower level of MT-Ab than unrecovered group,which is statistical significant at level of a=0.1(P=0.067).This study suggests that there is obvious dose-respond relation between environmental cadmium exposure and renal dysfunction,however,no such relation is observed between the exposure and plasma level of MT-Ab.Subjects with higher MT-Ab levels more readily develop cadmium induced renal dysfunction.Thus,the levels of plasma MT-Ab can be used as a biomarker of susceptibility to renal dysfunction in environmental cadmium exposure.