Abstract
The effect ofN-benzyl-d-glucamine dithiocarbamate (BGD) on the renal toxicity induced by acute exposure to cadmium-metallothionein (Cd-MT) in rats was studied. Rats were injected intraperitoneally with BGD (400 μmol/kg) 6, 12, or 24 h after intraperitoneal injection of Cd-MT (1.78 μmol Cd as Cd-MT/kg) and thereafter they received three injections of BGD (400 μmol/kg) daily for 3 days. Urinary protein concentration and aspartate aminotransferase (AST) activity significantly increased 1 day after Cd-MT treatment and decreased to control levels at 9 days after the treatment. Urinary excretion of glucose and amino acids rose gradually reaching maximum levels 5 days after Cd-MT treatment and returned to the control levels at 9 days. BGD injection significantly reduced the increases in the urinary excretion of protein, AST, glucose and amino acid, which were produced by Cd-MT treatment. Significant increases in urine volume were observed after Cd-MT treatment. BGD injection inhibited the increase in urine volume caused by Cd-MT treatment. A long time interval (12 and 24 h) between the administrations of Cd-MT and BGD resulted in a decreased protective effect of BGD against Cd-MT-induced renal damage. Following Cd-MT injection, the major route of excretion of cadmium (Cd) was via the urine and the kidney was the major site of accumulation of Cd. BGD injection remarkably increased the urinary excretion of Cd, resulting in a significant reduction in the kidney Cd concentration. The results of this study indicate that BGD injection is effective in decreasing the Cd concentration in the kidney, resulting in the protective effect on Cd-MT-induced renal damage.
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References
Cain K, Holt DE (1983) Studies of cadmium-thionein induced nephropathy: time course of cadmium-thionein uptake and degradation. Chem-Biol Interact 43: 223–237
Cherian MG (1980) Chelation of cadmium with BAL and DTPA from cadmium exposed rats. Nature (London) 287: 871–872
Cherian MG, Rodgers K (1982) Chelation of cadmium from metallothionein in vivo and its excretion in rats repeatedly injected with cadmium chloride. J Pharmacol Exp Ther 222: 699–704
Cherian MG, Shaikh ZA (1975) Metabolism of intravenously injected cadmium-binding protein. Biochem Biophys Res Commun 65: 863–869
Cherian MG, Goyer RA, Delaquerriere-Richardson L (1976) Cadmium metallothionein induced nephropathy. Toxicol Appl Pharmacol 38: 399–408
Feldman SL, Failla ML, Cousins RJ (1978) Degradation of rat liver metallothioneins in vitro. Biochim Biophys Acta 544: 638–646
Friberg L, Piscator M, Nordberg GF, Kjelstrom T (1974) Cadmium in the environment, 2nd edn, CRC Press, Cleveland, Ohio, p 130
Gale GR, Atkins LM, Walker EM, Smith AB, Hynes JB (1983a) Comparative effects of three dialkyldithiocarbamates on acute toxicity, organ distribution, and excretion of cadmium. Ann Clin Lab Sci 13: 207–216
Gale GR, Atkins LM, Walker EM, Smith AB (1983b) Effects of combined treatment with diethyldithiocarbamate and diethylenetriamine-pentaacetate on organ distribution and excretion of cadmium. Ann Clin Lab Sci 13: 425–431
Gale GR, Atkins LM, Walker EM, Smith AB, Jones MM (1983c) Mechanism of diethyldithiocarbamate, dihydroxyethyldithiocarbamate, and dicarboxymethyldithiocarbamate action on distribution and excretion of cadmium. Ann Clin Lab Sci 13: 474–481
Gale GR, Walker EM, Smith AB (1983d) Effects of combined treatment with diethyldithiocarbamate and dihydroxyethyldithiocarbamate on distribution and excretion of cadmium. Res Commun Chem Pathol Pharmacol 41: 293–302
Gale GR, Atkins LM, Smith AB, Jones SG, Jones MM (1987) Amphipathic dithiocarbamates as cadmium antagonists:N-cyclohexyl-N-sulfonatoalkyl derivatives. Res Commun Chem Pathol Pharmacol 58: 371–391
Goyer RA, Cherian MG, Delaquerriere-Richardson L (1984) Correlation of parameters of cadmium exposure with onset of cadmium-induced nephropathy in rats. J Environ Pathol Toxicol Oncol 5: 89–100
Jin T, Leffler P, Nordberg GF (1987) Cadmium-metallothionein nephrotoxicity in the rat: transient calcuria and proteinuria. Toxicology 45: 307–317
Kagi JHR, Vallee BL (1960) Metallothionein: A cadmium- and zinc-containing protein from equine renal cortex. J Biol Chem 235: 3460–3465
Kojima S, Kiyozumi M (1974) Studies on poisonous metals. I. Transfer of cadmium chloride across rat small intestine in vitro and effect of chelating agents on its transfer. Yakugaku Zasshi 94: 695–701
Kojima S, Kiyozumi M, Saito K (1976) Studies on poisonous metals. II. Effect of chelating agents on excretion of cadmium through bile and gastrointestinal mucosa in rats. Chem Pharm Bull 24: 16–21
Kojima S, Kaminaka K, Kiyozumi M, Honda T (1986a) Comparative effects of three chelating agents on distribution and excretion of cadmium in rats. Toxicol Appl Pharmacol 83: 516–524
Kojima S, Kaminaka K, Kiyozumi M, Honda T (1986b) Effects of chelating agents on biliary and urinary excretion and tissue distribution of cadmium in rats. Toxicol Lett 34: 41–46
Kojima S, Kiyozumi M, Honda T, Kaminaka K, Oda Y, Senba Y (1987a) Effect ofN-benzyl-d-glucamine dithiocarbamate on distribution and excretion of cadmium in rats. Toxicology 45: 93–102
Kojima S, Kiyozumi M, Honda T, Senba Y, Kaminaka K, Ohnishi M (1987b) Studies on poisonous metals. XVIII. Effects of several dithiocarbamates on tissue distribution and excretion of cadmium in rats. Chem Pharm Bull 35: 3838–3844
Maitani T, Watahiki A, Suzuki KT (1986) Acute renal dysfunction by cadmium injected with cysteine in relation to renal critical concentration of cadmium. Arch Toxicol 58: 136–140
Min K-S, Hatta A, Onosaka S, Ohta N, Okada Y, Tanaka K (1987) Protective role of renal metallothionein against Cd nephropathy in rats. Toxicol Appl Pharmacol 88: 294–301
Murakami M, Cain K, Webb M (1983) Cadmium-metallothionein-induced nephropathy: a morphological and autoradiographic study of cadmium distribution, the development of tubular damage and subsequent cell regeneration. J Appl Toxicol 5: 237–243
Nippon Shokaki Gakkai (1964) Standard procedures for liver function testes. Japan J Gastroenterol 61: 621–630
Nomiyama K (1973) Early detection of chronic cadmium poisoning. Japan Med J 2597: 132
Nordberg GF, Goyer RA, Nordberg M (1975) Comparative toxicity of cadmium-metallothionein and cadmium chloride on mouse kidney. Arch Pathol 99: 192–197
Nordberg GF, Piscator M, Lind B (1971) Distribution of cadmium among protein fractions of mouse liver. Acta Pharmacol Toxicol 29: 456–470
Piscator M (1962) Proteinuria in chronic cadmium poisoning. II. The applicability of quantitative and qualitative methods of protein determination for the demonstration of cadmium proteinuria. Arch Environ Health 5: 325–332
Sato M, Sasaki M, Nagai Y (1987) Increased urinary excretion of collagen metabolites in cadmium-metallothionein nephropathy. Arch Toxicol 61: 116–119
Shibata S (1971) Rinshokagaku no jitsugi, Teiryohen, Kaneharashuppan Co., Ltd, Tokyo
Shinobu LA, Jones SG, Jones MM (1984) SodiumN-methyld-glucamine dithiocarbamate and cadmium intoxication. Acta Pharmacol Toxicol 54: 189–194
Squibb KS, Pritchard JB, Fowler BA (1984) Cadmium-metallothionein nephropathy: relationships between ultrastructural/ biochemical alterations and intercellular cadmium binding. J Pharmacol Exp Ther 229: 311–321
Sugihira N, Sagai M, Suzuki KT (1987) Renal damage induced by cadmium-metallothionein: effects on biochemical indicators. Toxicology 44: 1–11
Suzuki CAM, Cherian MG (1987) Renal toxicity of cadmium-metallothionein and enzymuria in rats. J Pharmacol Exp Ther 240: 314–319
Suzuki KT, Maitani T, Takenaka S (1979) Fate of intraperitoneally injected liver metallothionein in rat kidney. Chem Pharm Bull 27: 647–653
Tanaka K, Sueda K, Onosaka S, Okahara K (1975) Fate of109Cd-labelled metallothionein in rats. Toxicol Appl Pharmacol 33: 258–266
Terhaar CJ, Vis E, Roudabush RL, Fasset D (1965) Protective ef-fects of low doses of cadmium chloride against subsequent high doses in the rat. Toxicol Appl Pharmacol 7: 700
Webb M, Etienne AT (1977) Studies on the toxicity and metabolism of cadmium-thionein. Biochem Pharmacol 26: 25–30
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This work was presented in part at the 14th Symposium on Environmental Pollutants and Toxicology, Kumamoto, Japan, November 11, 1988
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Kojima, S., Ono, H., Furukawa, A. et al. Effect of N-benzyl-d-glucamine dithiocarbamate on renal toxicity induced by cadmium-metallothionein in rats. Arch Toxicol 64, 91–96 (1990). https://doi.org/10.1007/BF01974392
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DOI: https://doi.org/10.1007/BF01974392