Renal proximal tubule segment-specific nephrotoxicity: an overview on biomarkers and histopathology.
The correspondence between histopathological findings and segment-specific biomarkers was investigated in rats treated with segment-specific nephrotoxicants. Male Wistar rats were treated with a single injection of K2Cr2O7 (25 mg/kg s.c. in saline), cis-Pt (10 mg/kg i.p. in buffered MSO) or HCBD (100 mg/kg i.p. in corn oil). Twenty-four and 48 hours after treatment, the rats were sacrificed and the kidneys were drawn for histopathological and biochemical evaluation, i.e., GS activity in renal cortex and PAH uptake in renal cortical slices. Histopathological findings show that cis-Pt and HCBD cause diffuse necrosis of S3 segment of proximal tubules in the outer stripe of outer medulla, respectively. On the contrary, K2Cr2O7 damages exclusively S1-S2 segments, inducing vacuolization at 24 hr and diffuse necrosis at 48 hr after treatment. GS activity in renal tissue is significantly decreased after HCBD and cis-Pt, but not K2Cr2O7 treatment. In contrast, PAH uptake is significantly reduced by K2Cr2O7, but not by cis-Pt or HCBD treatment (even if HCBD causes a slight decrease 48 hr after treatment). The evidence of this study confirms the high specificity of GS activity as marker of S3 segment injury, that PAH uptake is prevalently active in the S1-S2 segments, and that there is complete correspondence among segment-specific nephrotoxicants, biomarkers of segment-specific damage, and histopathological findings.
Cristofori
Patrizia
P
GlaxoSmithKline, Verona, Italy.
Zanetti
Edoardo
E
Fregona
Dolores
D
Piaia
Alessandro
A
Trevisan
Andrea
A
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D015415:Biomarkers / Q000378:metabolism; D002070:Butadienes / Q000009:adverse effects; D002424:Caustics / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects; D005659:Fungicides, Industrial / Q000009:adverse effects; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011192:Potassium Dichromate / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics / Q000009:adverse effects*; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000970:Antineoplastic Agents; D015415:Biomarkers; D002070:Butadienes; D002424:Caustics; D005659:Fungicides, Industrial; D015262:Xenobiotics; C001335:hexachlorobutadiene; D005974:Glutamate-Ammonia Ligase; D002945:Cisplatin; D011192:Potassium Dichromate; D010130:p-Aminohippuric Acid