p-Aminohippuric acid (PAH) accumulation impairment after treatment with segment-specific nephrotoxicants

Hexachloro-1:3-butadiene (HCBD) and potassium dichromate (Cr6+) are chemicals toxic for the pars recta and the pars convoluta, respectively. PAH accumulation takes place in the basolateral membrane of the proximal tubule and its impairment is a sign of damage of the membrane. Segmentary localization of PAH accumulation is discussed, because different authors localize it in the pars convoluta only or in both. HCBD 100 mg/kg i.p. or Cr6+ 25 mg/kg s.c. were injected in two months old male Wistar rats. Twenty four and 48 hours after treatment, rats were sacrificed and kidneys were removed and prepared to determine PAH accumulation in renal cortical slices; at the same time, histological evaluation of the kidney was performed. Table shows percent variation and statistical significance to the respect of the controls of PAH accumulation after treatment with both chemicals (24 hs: HCBD 92%, Cr6+ 68% (p<0.01); 48 hs: HCBD 64% (p<0.01), Cr6+ 41% (p<0.001). Histological findings show that HCBD causes diffuse necrosis of the pars recta (at the both time of examination) whereas Cr6+ causes multifocal (24 hours) and diffuse (48 hours) vacuolization of the pars convoluta. At 24 and 48 hours, the chemicals don’t affect other district of the nephron. HCBD and Cr6+ cause PAH accumulation impairment, though Cr6+ treatment produces an earlier and more relevant decrease of PAH uptake. In conclusion, the effects of segment-specific nephrotoxicants on in vitro PAH accumulation after in vivo treatment show that this function of the proximal tubule is localized in the pars convoluta and in the pars recta, though organic anion accumulation in the pars convoluta is more sensitive to the toxic effects.