γ-aminobutyric acid specifically inhibits progression of tubular fibrosis and atrophy in nephrectomized rats

Abstract

γ-Aminobutyric acid (GABA) was administered orally to rats for 60 d after excision of five-sixths of their kidney volume. A decrease in renal function parameters was observed in these nephrectomized rats. However, the administration of GABA ameliorated renal dysfunction, and a longer administration period of GABA increased its protective effect. In addition, tubular fibrosis was markedly increased at 10 and 60 d in nephrectomized control rats, while GABA administration for 10 d reduced tubular fibrosis to the normal level. Tubular atrophy was markedly induced by nephrectomy, and was significantly reduced by the administration of GABA at 60 d. Furthermore, the nephrectomized control rats exhibited an increased expression level of transforming growth factor-β1, where GABA significantly decreased it after administration for 10 d. The expression of fibronectin in the tubuli of rats administrated GABA for 60 d was completely and dose-dependently reduced as compared with nephrectomized control rats. However, the improvement effects in glomeruli were less. We also found that GABAA and GABAB receptors were specifically localized in tubuli. Specific agonists for GABAA and GABAB receptors improved renal function. These results suggest that GABA may have a beneficial effect on renal function in nephrectomized rats by inhibiting fibrosis and atrophy primarily in tubuli, and that it ameliorates losses of renal function in renal failure. © 2007 Pharmaceutical Society of Japan.