Tubular segment-specific biomarkers of nephrotoxicity in the rat.
Segment-specific localization of p-aminohippuric acid accumulation and glutamine synthetase activity along the proximal tubule was investigated in kidneys of rats treated with segment-specific nephrotoxicants such as potassium dichromate (pars convoluta) and hexachloro-1:3-butadiene (pars recta). Potassium dichromate and the highest dose (200 mg/kg b.w.) of hexachloro-1:3-butadiene caused a significant, dose-dependent decrease of p-aminohippuric acid uptake in the renal cortical slices 24 and 48 h after the treatment. In contrast, hexachloro-1:3-butadiene and only the highest dose (40 mg/kg b.w.) of potassium dichromate, caused a significant dose-dependent decrease of glutamine synthetase activity in the kidney beginning 24 h after treatment. Finally, potassium dichromate and the highest dose (200 mg/kg b.w.) of hexachloro-1:3-butadiene (48 h after the treatment) caused a significant dose-dependent loss of kidney protein content. The results suggest that p-aminohippuric acid accumulation is localized in the pars convoluta and confirm that glutamine synthetase is in the pars recta of the rat proximal tubule. p-Aminohippuric acid uptake impairment and glutamine synthetase activity loss caused by the highest doses of hexachloro-1:3-butadiene and potassium dichromate, respectively, suggests that high doses of segment-specific chemicals may involve other portions of the proximal tubule; in addition, the decrease of glutamine synthetase activity caused by potassium dichromate may be related to the protein content loss.
Trevisan
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A
Laboratory of Industrial Toxicology, Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, I-35128 Padova, Italy. atrevi@ux1.unipd.it
Giraldo
M
M
Borella
M
M
Bottegal
S
S
Fabrello
A
A
D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002070:Butadienes / Q000009:adverse effects*; D002424:Caustics / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000009:adverse effects*; D005974:Glutamate-Ammonia Ligase / Q000032:analysis*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D011192:Potassium Dichromate / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D010130:p-Aminohippuric Acid / Q000032:analysis*
D015415:Biomarkers; D002070:Butadienes; D002424:Caustics; D005659:Fungicides, Industrial; C001335:hexachlorobutadiene; D005974:Glutamate-Ammonia Ligase; D011192:Potassium Dichromate; D010130:p-Aminohippuric Acid