Study On Combined Nephrotoxicity Of Cadmium And Arsenic

Objective:The combined nephrotoxicity of cadmium (Cd) and arsenic (As) and an assessment of the dose response relationships between Cd and As co-exposure and renal dysfunction have been studied in both the populations environmentally or occupationally co-exposed to Cd and As and experimental animals. The benchmark dose (BMD) and the lower confidence limit on the benchmark dose (BMDL) of urinary cadmium (UCd) and arsenic (UAs) were estimated. It could provide toxicological data from humans and animals to formulate the health standard for As and Cd co-exposure. Methods:The concentration UAs and UCd were used as exposure biomarkers. Urinary β 2-microglobulin (Uβ 2-MG), N-acetyl-β-glucosaminidase (UNAG), albumin (UALB) and metallothionein (UMT) were determined as biomarkers of renal dysfunction. Using semi-quantitative RT-PCR, gene expression of MT-1 and MT-2 in renal cortex were assayed. Results:There were significant differences in UCd and UAs concentration between residents living in the polluted areas and the control area, and these differences were related to the extent of co-exposure to Cd and As. It was also obvious that the levels of Uβ 2-MG, UNAG, UALB and UMT in the exposed groups were significantly higher than that in the control group (P<0.01). The dose response relationships between Cd and As co-exposure and renal adverse effects was found. Cd and inorganic arsenic (In-As,in environment and workplace) can cause renal dysfunction including in both glomerulus and tubules. The tubular damage was caused by mostly Cd exposure and the glomerular damage was by mostly In-As exposure. The combined nephrotoxicity of Cd and In-As were additive and/or synergistic effect. But there has not combined effect between Cd and organic arsenic (Or-As,in seafood) and Or-As may restrain nephrotoxicity of Cd during the long-term and co-exposure of Or-As and Cd in humans. The BMDL of UAs and UCd for a 10% level of risk above the background level were estimated as 96.12μg/g creatinine and 1.06μg/g creatinine for general population mainly In-As exposed. In such case, UALB may be as a sensitive biomarker for those III 复旦大学博士生毕业论文 镉,砷对肾脏的联合毒性研究 英文摘要 people mainly exposed to In-As. For general population mainly Cd exposed, the BMDL of UCd and UAs for a 10% level of risk above the background level were estimated as 5.17μg/g creatinine and 175.84μg/g creatinine and Uβ 2-MG may be as sensitive biomarker. For workers occupationally co-exposed to Cd and In-As, the BMDL of UCd and UAs for a 10% level of risk above the background level were estimated as 1.74μg/g creatinine and 37.45μg/g creatinine and UNAG and UMT may be as sensitive biomarkers. In animal study, the BMDL of UCd and UAs was estimated as 1.60μg/g creatinine and 71.63mg/g creatinine, respectively. There were significant differences in gene expression of MT-1 and MT-2 in renal cortex from rats with drinking water containing Cd and/or In-As and these differences were related to the extent of intake of Cd and In-As.