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.