Heparin treatment reduces glomerular injury in rats with adriamycin-induced nephropathy but does not modify tubulointerstitial damage or the renal production of transforming growth factor-beta.
In this study we investigated the effect of heparin on renal injury and renal transforming growth factor-beta (TGF-beta) production in adriamycin (AD)-injected rats. Thirty-nine female Wistar rats were injected with AD (3.5 mg/kg body weight, i.v.) and 27 with 0.15 M NaCl solution (group C). Fifteen days later we started to inject heparin, 500 U/day, s.c., in 20 of the AD-injected animals (AD-H group). Three months after beginning treatment, urine samples were collected to quantify albumin, creatinine and TGF-beta. The rats were killed and the kidneys removed for histological, immunohistochemical, ELISA and RNA studies. All AD-injected animals showed structural renal changes (p < 0.05). However, the glomerular alterations were less intense in rats from group AD-H (p < 0.05). The percentage of glomerulosclerosis was 0.11 +/- 0.08 in group C, 14.7 +/- 12.8 in group AD (treated only with AD) and 3.42 +/- 2.3 in group AD-H. Renal cortex immunostaining for TGF-beta and mRNA content of this polypeptide was higher in both groups of animals injected with AD compared to controls (p < 0.05). These animals also presented a higher rate of urinary TGF-beta excretion (p < 0.05), which was 202 +/- 11 in group C, 1,103 +/- 580 in group AD and 1,564 +/- 328 pg/mg Ucreat in group AD-H. However, TGF-beta activity in the glomerular-conditioned media from the rats of group AD was higher than in the glomerular-conditioned media from the rats of group AD-H. In conclusion, treatment with heparin reduces glomerular damage in rats with AD-induced nephropathy but does not modify tubulointerstitial lesions or the renal production of TGF-beta.
Baroni
E A
EA
Department of Physiology, Medical School of Ribeirão Preto, Brazil.
Costa
R S
RS
da Silva
C G
CG
Coimbra
T M
TM
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D004317:Doxorubicin; D016232:Endothelins / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000473:pathology*; D011507:Proteinuria; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000652:urine
D016232:Endothelins; D005353:Fibronectins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D004317:Doxorubicin; D006493:Heparin; D003404:Creatinine