Effect of depot zinc treatment on cisplatin toxicity and trance element metabolism in rats

Conference · Fri Mar 15 04:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5174555

Nelson, K L; Reeves, P G ^[1]

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1. Dept. of Agriculture, Grand Forks, ND (United States)

Cisplatin (CDDP), an effective chemotherapeutic drug, is toxic to kidneys. Previous reports suggests that the induction of kidney metallothionein (MT) by trace elements is protective against CDDP toxicity in mice. This study was designed to determine if depot Zn treatment would induce synthesis of kidney MT and prevent CDDP toxicity in rats. Young adult male rats were given s.c. doses of 90 mg Zn/kg BW every other day for 10 days. Control rats were given oil only. At day 7 some rats from each group were given i.p. injections of 5 mg CDDP/kg BW. A third group of control rats were pair-fed to those receiving CDDP. Three days later tissues and serum were removed for analyses. The concentration of MT in the kidneys of rats injected with Zn was 4 times higher than in rats injected with oil alone. Serum urea and creatinine were elevated in CDDP-treated rats injected with Zn, which indicates that the increase in kidney MT did not protect them from CDDP toxicity. Partly as a result of high kidney MT, kidney Zn was 2-fold higher in Zn-injected then control rats. CDDP treatment itself elevated kidney MT, but so did pair-feeding. Cu loading has been shown to protect mice from CDDP toxicity. However, both serum Cu and kidney Cu were elevated in Zn-treated rats compared to controls. Still, the kidneys showed signs of malfunction. The major conclusion from this study is that, unlike the results observed in mice, increasing MT concentrations in the kidneys of rats by depot Zn administration does not protect them from CDDP toxicity.

• OSTI ID: 5174555
• Report Number(s): CONF-9104107--
• Conference Information: Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 5:5
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
DRUGS
ELEMENTS
KIDNEYS
MAMMALS
METABOLISM
METALLOPROTEINS
METALLOTHIONEIN
METALS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RATS
RODENTS
SYNTHESIS
TOXICITY
TRACE AMOUNTS
VERTEBRATES
ZINC