Tubular cell lesion, albuminuria, and renal albumin handling in rats treated with adriamycin.
Several lines of evidence have suggested that renal handling of proteins in rats with several nephropathies may contribute to the tubulointerstitial damage observed in these animals. It has been suggested that proteins filtered by the glomeruli may be toxic for tubule cells. The aim of this study was to investigate the relationship between albuminuria and tubular lesions observed in rats during the first two weeks after treatment with adriamycin (AD). Thirty female Wistar rats were injected intravenously with adriamycin at the dose of 3.5 (17 rats) or 5mg/kg body weight (13 rats), and 7 were injected with 0.15 M NaCl (control group). Seven days later, we replaced drinking water with a 0.10 M sodium bicarbonate solution for 6 of the animals injected with 5 mg/kg adriamycin (group AD-B). Urine samples were collected before and 7 and 15 days after treatment to quantify albumin. The rats were killed 7 and 18 days after the injections, and the kidneys removed for immunohistochemical study. We observed a significant increase in urinary albumin excretion 15 days after AD injection (3.5 mg/kg), but not 7 days after AD. However, in the animals injected with 5.0 mg/kg AD (group AD-5) the increase in albuminuria was observed as early as on day 7. The immunohistochemical studies showed increased vimentin and albumin immunoreaction in the tubular cells of the renal cortex from the kidneys of rats injected with 3.5 mg/kg (group AD-3) only 18 days after treatment (p < 0.05), whereas in the animals treated with 5 mg/kg AD these immunohistochemical alterations were more intense. However, treatment with sodium bicarbonate attenuated the tubular lesions and reduced albumin reabsorption in adriamycin-treated rats. In conclusion, these experiments showed a relationship between albuminuria and tubular lesions in adriamycin-treated rats.
Galli
L G
LG
Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Volpini
R A
RA
Costa
R S
RS
da Silva
C G
CG
Coimbra
T M
TM
D000419:Albuminuria / Q000139:chemically induced*; D000704:Analysis of Variance; D000818:Animals; D003404:Creatinine / Q000097:blood / Q000652:urine; D046508:Culture Techniques; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin; D005260:Female; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology*; D009395:Nephritis, Interstitial / Q000473:pathology*; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity
D004317:Doxorubicin; D003404:Creatinine