Effect of TGF-1 antisense oligodeoxynucleotide on renal function in chronic renal failure rats

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Abstract:

Abstract

Aim: The aim of the present study was to investigate the effectiveness of transforming growth factor (TGF)-1 antisense oligodeoxynucleotides (ODN) in ameliorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF). Methods: Saline, puromycin, puromycin+TGF-1 antisense ODN or puromycin+scrambled ODN were administered to unilaterally nephrectomized rats. Renal hemodynamic and excretory measurements were taken in the anaesthetized rats that had undergone surgical procedure. Results: It was observed that in the CRF rats, there was a marked reduction in the renal blood flow (RBF), glomerular filtration rate (GFR), severe proteinuria, and almost 6-fold increased fractional excretion of sodium (FE Na+) as compared to that in the control rats (all P<0.05). It was further observed that in the CRF rats, the treatment with TGF-1 antisense, but not scrambled ODN, markedly attenuated the reduction of RBF, GFR, and proteinuria and markedly prevented the increase of the FE Na+ (all P<0.05). In addition, the renal hypertrophy in the CRF group (P<0.05 vs non-renal failure control) was markedly attenuated after treatment with TGF-1 antisense ODN (P<0.05). Focal segmental glomerulosclerosis was evident only in the untreated and scrambled ODN-treated CRF groups. An interesting observation of this study was that in the CRF rats, although there was marked attenuating and preventive effects of the TGF-1 antisense ODN on the deteriorated renal functions, the antisense treatment did not cause any marked change in the renal expression of TGF-1 at the protein level. Conclusion: Collectively, the data obtained suggests that TGF-1 antisense ODN possesses beneficial effects in puromycin-induced chronic renal failure and that the deterioration in morphology and impaired renal function in this pathological state is in part dependent upon the action of TGF-1 within the kidney.

Keywords: antisense oligodeoxynucleotides; chronic renal failure; renal function; transforming growth factor-1

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2008.00772.x

Affiliations: 1: Department of Pharmacology University of Malaya, Kuala Lumpur 50603, Malaysia 2: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia 3: Department of Pathology, University of Malaya, Kuala Lumpur 50603, Malaysia 4: Department of Physiology, University College Cork, Cork, Ireland

Publication date: April 1, 2008

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