Cadmium is an environmental and occupational hazard known to cause kidney damage after chronic exposure and to adversely affect the reproductive organs and liver in acute exposure situations. This element, which has known biological function, is accumulated with age and to a greater extent in females than in males. It is retained in liver, kidney and other tissues bound to metallothionein. This proposal is designed toxicity of cadmium. Studies in human materials will examine the relationship between tissue metal and metallothionein levels as affected by age, sex, smoking habit and disease conditions. The significance of urinary metallothionein as a biological indicator of cadmium exposure will be examined in occupationally exposed workers. Studies in resistant and susceptible strains of mice will evaluate the role of sex hormones in hepatic and testicular toxicity of cadmium. The role of sex hormones in hepatic metabolism of cadmium, metallothionein induction and toxicity will be further studied in primary cultures of mouse hepatocytes. Testicular cadmium-binding proteins will be isolated and characterized in an effort to explain the resistance of certain mouse strains to cadmium. With regards to the chronic toxicity of cadmium, the hypothesis that the females may be at greater risk of developing renal dysfunction will be tested in rats. The role of metallothionein-bound cadmium in the etiology of cadmium-induced renal dysfunction will be further examined. It is expected that this research proposal will yield new information that will be of use in understanding some of the risk factors in cadmium toxicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES003187-07
Application #
3250344
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1983-02-01
Project End
1993-07-31
Budget Start
1991-02-01
Budget End
1993-07-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Rhode Island
Department
Type
Schools of Pharmacy
DUNS #
135531015
City
Kingston
State
RI
Country
United States
Zip Code
02881
Tang, Weifeng; Xie, Jianxun; Shaikh, Zahir A (2006) Protection of renal tubular cells against the cytotoxicity of cadmium by glycine. Toxicology 223:202-8
Tang, W; Shaikh, Z A (2001) Renal cortical mitochondrial dysfunction upon cadmium metallothionein administration to Sprague-Dawley rats. J Toxicol Environ Health A 63:221-35
Limaye, D A; Shaikh, Z A (1999) Cytotoxicity of cadmium and characteristics of its transport in cardiomyocytes. Toxicol Appl Pharmacol 154:59-66
Shaikh, Z A; Zaman, K; Tang, W et al. (1999) Treatment of chronic cadmium nephrotoxicity by N-acetyl cysteine. Toxicol Lett 104:137-42
Shaikh, Z A; Northup, J B; Vestergaard, P (1999) Dependence of cadmium-metallothionein nephrotoxicity on glutathione. J Toxicol Environ Health A 57:211-22
Shaikh, Z A; Tang, W (1999) Protection against chronic cadmium toxicity by glycine. Toxicology 132:139-46
Tang, W; Kido, T; Gross, W A et al. (1999) Measurement of cadmium-induced metallothionein in urine by ELISA and prevention of overestimation due to polymerization. J Anal Toxicol 23:153-8
Shaikh, Z A; Jordan, S A; Tang, W (1999) Protection against chronic cadmium toxicity by caloric restriction. Toxicology 133:93-103
Shaikh, Z A; Vu, T T; Zaman, K (1999) Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants. Toxicol Appl Pharmacol 154:256-63
Tang, W; Sadovic, S; Shaikh, Z A (1998) Nephrotoxicity of cadmium-metallothionein: protection by zinc and role of glutathione. Toxicol Appl Pharmacol 151:276-82

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