Evaluation of aging influence on renal toxicity caused by segment-specific nephrotoxicants of the proximal tubule in rat.
Little is known concerning the sensitivity of aged rats to xenobiotics inducing kidney damage. To increase this knowledge, the age-dependent response of the kidney to hexachloro-1 : 3-butadiene (HCBD) or potassium dichromate (chromate) was investigated. Rats were treated at different ages with a single dose of segment-specific nephrotoxicants of the proximal tubule, chosen on the basis of their specificity for S(3) and for S(1)-S(2) segments, respectively. The toxicological impact of these xenobiotics has been evaluated through biochemical and genomic markers, and histopathological investigation of kidney samples. HCBD treatment induced tubular necrosis of the S(3) segment of the proximal tubule associated with changes of toxicological markers unrelated to the age. In contrast, chromate treatment induced an increased kidney damage related to the rat age. In fact, histopathological investigation revealed that at 1 month of age tubular vacuolar degeneration was seen affecting S(1)-S(2) segments of the proximal tubule, whereas at 3 months of age tubular necrosis occurred in the same segments associated with tubular dilation of the distal portions. Consistently, biochemical analysis confirmed a direct correlation among genomic and biochemical marker variability and animal age. Altogether, the results show that during aging there is an increased sensitivity of kidney to chromate but not to HCBD-induced damage and evidence differential age-related selectivity of rats for nephrotoxic compounds. Significance for human risk assessment is discussed.
Zanetti
Edoardo
E
Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy.
Chiusolo
Arianna
A
Defazio
Rossella
R
Casartelli
Alessandro
A
Cappelletti
Eleonora
E
Bocchini
Nicola
N
Chiara
Federica
F
Cristofori
Patrizia
P
Trevisan
Andrea
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002070:Butadienes / Q000633:toxicity*; D007668:Kidney / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011192:Potassium Dichromate / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics / Q000633:toxicity
D015415:Biomarkers; D002070:Butadienes; D015262:Xenobiotics; C001335:hexachlorobutadiene; D011192:Potassium Dichromate