Renal amino acid transport in immature and adult rats during chromate and cisplatinum-induced nephrotoxicity.
The effects of sodium dichromate (chromate; 1 mg/100 g b. wt. s.c.) and cisdiamminedichloroplatinum(II) (CP; 0.6 mg/100 g b. wt. i. p.) on renal amino acid excretion and plasma amino acid composition were investigated in 10- and 55-day-old anaesthetised rats. On the basis of diuresis experiments on conscious rats the mentioned doses and times (1st day after chromate in both age groups and in 10-day-old rats after CP and 3rd day after CP in adult rats) were found out to be optimal for the characterisation of amino acid transport after heavy metal poisoning. Interestingly, in conscious 10-day-old rats chromate nephrotoxicity is not detectable after 1 mg/100 g b. wt. whereas all of the other experimental groups showed nephrotoxic effects of chromate and CP in conscious rats. Urine volumes are lower, but not significantly, in anaesthetised immature rats, independently of the administered nephrotoxin. But GFR is significantly lower in 10-day-old rats, both in controls and after CP, whereas after chromate GFR is significantly reduced only in adult rats and age differences disappeared. In principle the renal fractional excretion (FE) of amino acids was distinctly higher in immature rats as a sign of lower amino acid reabsorption capacity. Nevertheless, the amino acid plasma concentrations were relatively high in immature rats. However, both chromate and CP did not distinctly influence amino acid plasma concentrations. But in both age groups the administration of chromate and CP significantly decreased amino acid reabsorption capacity (increase in FE) as a sign of nephrotoxicity, most pronounced in adult rats after CP. The investigation of renal amino acid handling confirms (1) that both CP and chromate are nephrotoxins, (2) that CP was more nephrotoxic in 55-day-old animals compared to immature rats as could be demonstrated before using other parameters for nephrotoxicity testing and showed (3) that determination of renal amino acid handling is a highly sensitive marker for nephrotoxicity testing, especially in immature rats.
Fleck
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C
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Federal Republic of Germany. CFLE@mti-n.mti.uni-jena.de
Kretzschel
I
I
Sperschneider
T
T
Appenroth
D
D
D000367:Age Factors; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D015415:Biomarkers; D002840:Chromates / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000378:metabolism*
D000596:Amino Acids; D015415:Biomarkers; D002840:Chromates; D002945:Cisplatin