Tobramycin-induced changes in renal histology of fetal and newborn Sprague-Dawley rats.
Effects on renal development were studied using tobramycin (TBM) as a model compound. Pregnant Sprague-Dawley rats were injected i.p. with TBM at 30 or 60 mg/kg body weight/day on gestational days (GD) 10-19. Kidneys from dams and conceptuses were examined on GD 20 and on postnatal day (PD) 9. The dosing regimen caused in dams moderate proximal tubular alterations and increased concentrations in serum creatinine. Fetal kidneys showed granularity and swelling of proximal tubule cells at the 30 mg/kg dose, poor glomerular differentiation at the 60 mg/kg dose, increased glomerular density at both doses, and no changes on macroscopic examination at either dose. In newborns were observed a moderate developmental delay and tubular lesions at the higher dose, and dose-related increases of glomerular density and relative medullary area at both doses. All findings were more pronounced in males. A maturational disruption of the tubular structures possibly leading to increased glomerular density was attributed to TBM exposure during renal organogenesis in the rat.
Mantovani
A
A
Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Rome, Italy.
Macrì
C
C
Stazi
A V
AV
Ricciardi
C
C
Guastadisegni
C
C
Maranghi
F
F
D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D003404:Creatinine / Q000097:blood; D005260:Female; D007668:Kidney / Q000002:abnormalities / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D007678:Kidney Glomerulus / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D008297:Male; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains / Q000196:embryology; D014031:Tobramycin / Q000633:toxicity*
D003404:Creatinine; D014031:Tobramycin