Segmentary effects on the renal proximal tubule due to hexachloro-1,3-butadiene in rats: biomarkers related to gender.

Renal tissue biomarkers (glutamine synthetase and p-aminohippuric acid uptake) were studied in male and female rats after treatment with hexachloro-1,3-butadiene. Reduced glutathione content was also determined in liver and kidney. Histopathological examination (light microscopy) was then performed. The aim was to define sex differences in nephrotoxic effects caused by the solvent i.p. injected at 50, 100, and 200 mg kg-1 dose. The rats were sacrificed 24 and 48 h after treatment; after 24 h a significant (P<0.05) dose-dependent depletion of liver reduced glutathione was observed in male rats only; after 48 h male and female rats showed a significant (P<0.05) increase at 50 and 100 mg kg-1 doses. Reduced glutathione in the kidney was increased in male but not in female rats 24 and 48 h after treatment. Glutamine synthetase activity in renal tissue showed a significant (P<0.05) dose-dependent decrease 24 and 48 h after treatment in both sexes, but it was significantly (P<0.05) greater in female rats after 48 h. p-Aminohippuric acid uptake in renal cortical slices appeared significantly (P<0.05) decreased in both sexes at the higher dose 24 h after treatment but this was significantly (P<0.05) greater in female rats. A further significant (P<0.05) impairment was observed after 48 h in males treated with a 200 mg kg-1 dose. In addition, a slight but significant (P<0.05) loss of p-aminohippuric acid uptake was observed 48 h after treatment with 100 mg kg-1 dose in both sexes. Light microscopy showed that pars recta of the proximal tubule was mainly affected and tubular damage increased according to dose and time, involving the inner medulla and cortex. In conclusion, female rats show a significantly earlier and higher susceptibility of the kidney to toxic effects of hexachloro-1,3-butadiene.