Histological and Urinalysis Assessment of Nephrotoxicity Induced by Mercuric Chloride in Normal and Uninephrectomized Rats
Part of the
Rochester Series on Environmental Toxicity
book series (RSET)
Assessment of the health threat to human populations that have been exposed to nephrotoxic metals requires accurate information about relationships between exposure and renal function. Currently, urinalysis is relied on heavily for the evaluation of impairment of renal function and for describing dose-response relationships in numans (Gotelli et al., 1985; Roels et al., 1981; Stonard et al., 1983; Thun et al., 1985). This is because urine is the one biological product of renal function that can be readily sampled in field studies. The rationale for using urinalysis is to detect the increased excretion of marker substances that are normally conserved by physiological mechanisms susceptible to injury by metals. The most useful urinary markers are those that reflect the severity of functional impairment and that can be detected in the early stages of renal toxicity, hopefully before irreversible injury has occurred. Many different urinary markers have been used; including glucose (Falck et al., 1983; Tohyama et al., 1982) amino acids (Bernard et al., 1979; Buchet et al., 1980; Clarkson and Kench, 1956; Thun et al., 1985) plasma proteins (Bernard et al., 1979; Buchet et al., 1980; Falck et al., 1983; Roels et al., 1981; Stonard et al., 1983; Thun et al., 1985) and cellular enzymes (Bernard et al., 1979; Buchet et al., 1980; Gotelli et al., 1985; Stonard et al., 1983). Clearly, the selection of urinary markers that are appropriate for the anticipated form of toxicity is important. Analytical procedures that enable the investigator to describe variability within the urinalysis results due to variation in sampling time, urine flow rate and body mass of the subjects being studied are also required for accurate interpretation of urinalysis data.
KeywordsToxicity Mercury Cadmium Glutathione Uranium
Bernard, A., Buchet, J.P., Roels, H., Mason, P. and Lauwerys, R., 1979, Renal excretion of proteins and enzymes in workers exposed to cadmium, Eur. J. Clin. Invest.
, 9: 11–22.PubMedCrossRefGoogle Scholar
Berndt, W.O., Baggett, J.M., Blacker, A., and Houser, A., 1985, Renal glutathione and mercury uptake by kidney, Fund. Appl. Toxicol.
, 5: 832–839.CrossRefGoogle Scholar
Buchet, J.P., Roels, H., Bernard, A. and Lauwerys, R., 1980, Assessment of renal function of workers exposed to inorganic lead, cadmium or mercury vapor, J. Occup. Med.
, 22: 741–750.PubMedGoogle Scholar
Bricker, N.S. and Fine, L.G., 1981, The renal response to progressive nephron loss, in: “The Kidney,” B.M. Brenner and F.C. Rector, eds., pp. 1056–1096, W.B. Saunders Co., Philadelphia.Google Scholar
Clarkson, T.W. and Kench, J.E., 1956, Urinary excretion of amino acids by men absorbing heavy metals, Biochem. J.
, 62: 361–372.PubMedGoogle Scholar
Clarkson, T.W., and Magos, L., 1967, The effect of sodium maleate on the renal disposition and excretion of mercury, Br. J. Pharmacol. Chemother.
, 31: 560–567.PubMedGoogle Scholar
Dierckx, P.J., 1981, Urinary γ-glutamyltransferase as an indicator of acute nephrotoxicity in rats, Arch. Toxicol.
, 47: 209–215.CrossRefGoogle Scholar
Doumas, B.T., Watson, W.A. and Biggs, H.A., 1971, Albumin standards and the measurement of serum albumin with bromocresol green, Clin. Chim. Acta
, 31: 87–96.PubMedCrossRefGoogle Scholar
Falck, F.Y., Fine, L.J., Smith, R.G., McClathchey, K.D., Annesley, T., England, B. and Schork, A.M., 1983, Occupational cadmium exposure and renal status, Am. J. Ind. Med.
, 45: 541–549.CrossRefGoogle Scholar
Gotelli, C.A., Astolfi, E., Cox, C., Cernichiari, E. and Clarkson, T.W., 1985, Early biochemical effects or organic mercury fungicide on infants: “Dose makes the poison,” Science
, 227: 638–640.PubMedCrossRefGoogle Scholar
Gustafsson, J.E.C., 1976, Improved specificity of serum albumin determination and estimation of “acute phase reactants” by use of bromocresol green reaction, Clin. Chem.
, 22: 616–622.PubMedGoogle Scholar
Hursh, J.B., Clarkson, T.W., Nowak, TV., Pabico, R.C., McKenna, B.A., Miles, E., and Gibb, F.R., 1985, Prediction of kidney mercury content by isotope techniques, Kidney Int
., 27: 898–907.PubMedCrossRefGoogle Scholar
Klein, B. and Standaert, F., 1976, Fluorometry of plasma amino nitrogen with use of fluorescamine, Clin. Chem.
, 22: 413–416.PubMedGoogle Scholar
Leathwood, P.D., Gilford, M.K. and Plummer, D.T., 1972, Enzymes in rat urine: Lactate dehydrogenase, Enzymologia
, 42: 285–301.PubMedGoogle Scholar
Lockwood, T.D. and Bosmann, H.B., 1979, The use of urinary-N-acetyl-beta- glucosaminidase in human renal toxicology. I. Partial biochemical characterization and excretion in humans and release from the isolated perfused rat kidney, Toxicol.Appl. Pharmacol.
, 49: 323–336.PubMedCrossRefGoogle Scholar
Lowry, O.H. and Passoneau, J.V., 1972, in
: “A Flexible System of Enzymatic Analysis,” p. 172, Academic Press, New York.Google Scholar
Magos, L. and Clarkson, T.W., 1972, Atomic absorption determination of total, inorganic and organic mercury in blood, J. Assoc. Off. Anal. Chem.
, 55: 966–971.PubMedGoogle Scholar
Magos, L. and Stoychev, T., 1969, Combined effect of sodium maleate and some thiol compounds on mercury excretion and redistribution in rats, Br. J. Pharmacol.
, 35: 121–126.PubMedGoogle Scholar
Pesce, A.J. and First, M.R., 1979, “Proteinuria: An Integrated Review,” pp. 244–245, Marcel Dekker, Inc., New York.Google Scholar
Pfleiderer, G., 1970, Partical-bound aminopeptidase from pig kidney, in: “Methods in Enzymology,” Vol. 19, G.E. Perlmann and L. Lorand, ecfs., pp. 514–521, Academic Press, New York.Google Scholar
Richardson, R.J. and Murphy, S.D., 1975, Effect of glutathione depletion on tissue deposition of methylmercury in rats, Toxicol. Appl. Pharmacol.
, 31: 505–519.PubMedCrossRefGoogle Scholar
Roels, H.A., Lauwerys, R.R., Buchet, J.P. and Bernard, A., 1981, Environmental exposure to cadmium and renal function of aged women in three areas of Belgium. Environ. Res.
, 24: 117–130.PubMedCrossRefGoogle Scholar
Sigma Technical Bulletin (No. 57-UV), Sigma Chemical Co., St. Louis, MO, revised August, 1980.Google Scholar
Sigma Technical Bulletin (No. 56-UV), Sigma Chemical Co., St. Louis, MO, revised July, 1983.Google Scholar
Snedecor, G.W. and Cochran, W.G., 1967, “Statistical Methods,” Iowa State University Press, Ames, Iowa.Google Scholar
Stonard, M.D., Chater, B.V., Duffield, D.B., Nevitt, A.L., O’Sullivan, J.J. and Steele, G.T., 1983, An evaluation of renal function in workers occupationally exposed to mercury vapor, Int. Arch. Occup. Environ. Health
, 52: 177–189.PubMedCrossRefGoogle Scholar
Szasz, G., 1969, A kinetic photometric method of serum γ-glutamyltransferase, Clin. Chem.
, 15: 124–136.PubMedGoogle Scholar
Thun, M.J., Baker, D.B., Steenland, K., Smith, A.B., Halperin, W. and Berl, T., 1985, Renal toxicity in uranium mill workers, Scand. J. Work Environ. Health
, 11: 83–90.PubMedCrossRefGoogle Scholar
Tohyama, C. Shaikh, Z.A., Nogawa, K., Koyashi, E. and Honda, R., 1982, Urinary metallothionein is a new index of renal dysfunction in “Itai-itai” disease patient and other Japanese women environmentally exposed to cadmium, Arch. Toxicol.
, 50: 159–166.PubMedCrossRefGoogle Scholar
Trojanowska, B., Piotrowski, J.K. and Szendzikowski, S., 1971, The influence of thioacetamide on the excretion of mercury in rats, Toxicol. Appl. Pharmacol.
, 18: 374–386.PubMedCrossRefGoogle Scholar
Wright, P.J., Leathwood, P.D. and Plummer, D.T., 1972, Enzymes in rat urine: Alakaline phosphatase, Enzymologia
, 42: 317–327.PubMedGoogle Scholar
Zalups, R.K., Klotzbach, J.M. and Diamond, G.L., 1987, Enhanced accumulation of injected inorganic mercury in renal outer medulla after unilateral nephrectomy, Toxicol. Appl. Pharmacol.
, 89: 226–236.PubMedCrossRefGoogle Scholar
Zalups, R.K. and Diamond, G.L., 1987, Mercuric chloride-induced nephrotoxicity in the rat following unilateral nephrectomy and compensatory renal growth, Virchows Arch
. [B. Cell Pathol.], in press.Google Scholar
© Plenum Press, New York 1988