Age dependent differences in the functional and morphological impairment of kidney following cisplatin administration.
In adult rats the clearance of inulin, urinary p-aminohippurate (PAH) excretion, TmPAH, as well as PAH accumulation in renal cortical slices were decreased 48-72 h following 0.6 mg cisplatin/100 g body mass (b.m.). Morphological investigations showed changes preferentially in proximal tubules. Reduced inulin clearance is discussed to be rather the consequence of inulin back leak in destroyed tubules than of a real decrease in glomerular function. The ultrastructure of glomeruli, distal tubules, and collecting ducts was not affected by cisplatin (CP) in 10- and 55-day-old rats. In 10-day-old rats, inulin clearance and urinary PAH excretion remained unaffected by CP, whereas TmPAH and PAH accumulation in vitro were significantly decreased following CP. Most significant ultrastructural changes occurring in mitochondria are discussed to cause decreased PAH accumulation following CP. The high portion of PAH filtered in young rats masked this impairment of active PAH secretion. Lower nephrotoxicity in young rats seems to be caused by low state of a differentiation of cell structure and transport function.
Appenroth
D
D
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, GDR.
Gambaryan
S
S
Gerhardt
S
S
Kersten
L
L
Bräunlich
H
H
D000367:Age Factors; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000652:urine
D002945:Cisplatin; D010130:p-Aminohippuric Acid