In this study we investigated the effect of heparin on renal injury and renal transforming growth factor-β (TGF-β) 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-β. 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-β 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-β 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-β 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-β.

Keywords:
Adriamycin nephropathy, Heparin, Transforming growth factor-β, Glomerulosclerosis, Renal fibrosis, Proteinuria
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