Aging influences segment-specific toxicity of the proximal tubule caused by chemicals. I. Histopathological and biochemical findings

Senescence influences the kidney susceptibility to chemicals. The aim of the present research is to valuate the kidney effects caused by segment-specific nephrotoxicants during senescence. Male Wistar rats aged 6 or 14 weeks were treated with a single i.p. injection of hexachloro-1:3-butadiene (HCBD) 100 mg/kg b.w. in corn oil, or s.c. injection of potassium dichromate (Cr) in saline. After treatment, the urine was collected until 48 hours. Forty eight hours after treatment, the rats were sacrificed and kidney (for histology) and blood were collected. Creatinine and BUN in plasma, total proteins (TUP), NAG activity, glutamine synthetase (GS) activity, and creatinine in urine were determined. Histology shows that at 6-week of age HCBD causes moderate tubular necrosis of the pars recta resulting in a significant increase of plasma BUN and creatinine and high excretion of TUP, NAG and GS. At 14-week of age, in addition to the necrosis of pars recta, mild to moderate increase in tubular cytoplasmatic hyaline droplets were observed in the pars convoluta, whereas increase of biochemical parameters was lower than at 1.5 months of age. Cr induces mild to moderate tubular degeneration of pars convoluta at 6-week of age with a slight increase of creatinine but not BUN. Urinary biomarkers show an increase of TUP and NAG excretion but not of GS. In contrast, at 14-week of age moderate tubular necrosis of the pars convoluta and an extent of the damage to the pars recta (degeneration), distal tubules and collecting ducts (mild to moderate dilatation) were observed. According to the extent of the damage, creatinine and BUN in plasma and TUP in urine were highly increased. In conclusion, histopathological and biochemical findings confirm the segment-specific damage of the proximal tubule caused by HCBD (pars recta) and Cr (pars convoluta) in young rats. On the contrary, in 14-week rats the damage involves other regions of the nephron. These results show that age is a key factor influencing the severity of segment-specific nephrotoxicity.