Cisplatinum: effect of zinc acetate pretreatment on cellular uptake and interactions with cytosolic ligands.
Wistar rats were injected (i.p.) either with 5 mg cis-diamminedichloro-platinum-II (cis-DDP)/kg, or pretreated with Zn-acetate and then injected with cis-DDP. The Zn-pretreatment significantly increased the binding of Zn and Cu to both the renal and hepatic metallothioneins (MT), but the proportion of cytosolic Pt associated with MT in the kidney tissue was slightly reduced, and that in the liver showed no difference in comparison to rats treated with cis-DDP only. The results indicate that an increased MT biosynthesis by Zn-pretreatment may not correspondingly increase the binding of intracellular Pt to MT. In the Zn-acetate pretreated rats, the renal tissue and subcellular Pt levels were significantly lower (P less than 0.01) than that in untreated rats, although the liver levels showed practically no difference. It is suggested that Zn-acetate pretreatment prior to cis-DDP injection, may significantly reduce the cellular burden of Pt in the critical organ, the kidneys.
D000085:Acetates / Q000494:pharmacology*; D019342:Acetic Acid; D000818:Animals; D002945:Cisplatin / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D004347:Drug Interactions; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D008024:Ligands; D003300:Copper; D002945:Cisplatin; D019342:Acetic Acid