title: 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.
abstract: The aim of this study is to investigate the effect of sodium bicarbonate on doxorubicin-injected rats. Thirty female Wistar rats were injected with doxorubicin (3.5 mg/kg of body weight, intravenously) and 30 rats with 0.15 mol/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 killed, and the kidneys were removed for histological, morphometric, immunohistochemical, and RNA studies. All doxorubicin-injected animals showed structural 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 group AD (rats treated with doxorubicin only), and 4.38% +/- 1.9% in group AD-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. The immunostaining for TGF-beta in the renal cortex and glomeruli was more intense in the animals injected with doxorubicin only. A greater renal cortical TGF-beta messenger RNA content was observed in the animals injected with only doxorubicin that did not receive sodium bicarbonate (P < 0.05). These animals also presented a greater rate of urinary TGF-beta excretion reported as picograms of TGF-beta per milligram of urinary creatinine (P < 0.05), which was 202 +/- 11 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 group AD also showed higher immunostaining scores for vimentin and albumin in tubule cells (P < 0.05). In conclusion, treatment with sodium bicarbonate reduces structural renal damage, albumin reabsorption, and renal TGF-beta production in rats with doxorubicin-induced nephropathy.
authors.affiliation: Medical School of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil. tmcoimbr@fmrp.usp.br
authors.forename: E A
authors.initials: EA
authors.lastname: Baroni
authors.forename: R S
authors.initials: RS
authors.lastname: Costa
authors.forename: R
authors.initials: R
authors.lastname: Volpini
authors.forename: T M
authors.initials: TM
authors.lastname: Coimbra
mesh_terms: D000418:Albumins / Q000032:analysis; D000419:Albuminuria; D000818:Animals; D004317:Doxorubicin; D005260:Female; D005353:Fibronectins / Q000032:analysis; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis; D017693:Sodium Bicarbonate / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000652:urine; D014746:Vimentin / Q000032:analysis
chemical_list: D000418:Albumins; D005353:Fibronectins; D012709:Serum Albumin; D016212:Transforming Growth Factor beta; D014746:Vimentin; D004317:Doxorubicin; D017693:Sodium Bicarbonate