Sodium bicarbonate treatment reduces renal injury, renal production of transforming growth factor-beta, and urinary transforming growth factor-beta excretion in rats with doxorubicin-induced nephropathy

The aim of this study is to investigate the effect of sodium bicarbonate on doxorubicin-injected rats. Thirty female Wistar rats were injected with do xorubicin (3.5 mg/kg of body weight, intravenously) and 30 rats with 0.15 m ol/L of sodium chloride solution (group C). Fifteen days later, we replaced the drinking water with a 0.15-mol/L sodium bicarbonate solution for 10 of the animals injected with doxorubicin (group AD-B). Three months after the beginning of treatment, urine samples were collected to quantify albumin, creatinine, and transforming growth factor-beta (TGF-beta). The rats were k illed, and the kidneys were removed for histological, morphometric, immunoh istochemical, and RNA studies. All doxorubicin-injected animals showed stru ctural renal changes. However, these alterations were less intense in rats treated with doxorubicin plus sodium bicarbonate (P < 0.05). The percentage of glomerulosclerosis was 0.11% +/- 0.08% in group C, 14.7% +/- 12.8% in g roup AD (rats treated with doxorubicin only), and 4.38% +/- 1.9% in group A D-B, and the percentage of tubulointerstitial damage was 0.01% +/- 0.03% in group C, 54.6% +/- 20.3% in group AD, and 16.6% +/- 10.3% in group AD-B. T he immunostaining for TGF-beta in the renal cortex and glomeruli was more i ntense in the animals injected with doxorubicin only. A greater renal corti cal TGF-beta messenger RNA content was observed in the animals injected wit h only doxorubicin that did not receive sodium bicarbonate (P < 0.05). Thes e animals also presented a greater rate of urinary TGF-beta excretion repor ted as picograms of TGF-beta per milligram of urinary creatinine (P < 0.05) , which was 202 +/- II pg/mg in group C, 1, 103 +/- 580 pg/mg in group AD, and 299 +/- 128 pg/mg in group AD-B. However, albuminuria was more intense in the sodium bicarbonate-treated animals (P < 0.05). The animals from grou p AD also showed higher immunostaining scores for vimentin and albumin in t ubule cells (P < 0.05). In conclusion, treatment with sodium bicarbonate re duces structural renal damage, albumin reabsorption, and renal TGF-P produc tion in rats with doxorubicin-induced nephropathy. (C) 1999 by the National Kidney Foundation, Inc.