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Therapeutic effect of quinolone oxizime on fibrotic kidney diseases
Abstract
Purpose: To investigate the anti-fibrotic effect and mechanism of action of quinolone oxizime in vitro and in vivo.
Methods: Proliferation of renal fibroblasts was determined using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while laser confocal fluorescence microscope was used for immuno-cytochemical studies. Total TGF β1 was determined by enzyme linked immunosorbent assay (ELISA).
Results: Quinolone oxizime decreased the proliferation of renal fibroblasts in a dose-dependent manner (p < 0.05) in vitro. Proliferation of renal fibroblasts was 39, 63, 82, 95, 97 and 99 % on treatment with quinolone oxizime at doses of 10, 8, 6, 4, 2 and 1 μM, respectively, after 48 h. The expression of TGF β1 in the peripheral blood lymphocytes was reduced significantly by quinolone oxizime treatment. In the animal model of renal fibrosis, quinolone oxizime treatment decreased development of lesions, prevented tubular dilation and expansion of interstitium. After 30 days of quinolone oxizime treatment, tubulo-interstitial lesions were completely absent in rats in the 5 mg/kg treatment group. Moreover, quinolone oxizime treatment for 30 days inhibited accumulation of extracellular matrix and prevented renal injury in rats.
Conclusion: These results show that quinolone oxizime exhibits anti-fibrotic effects through targeting the expression of TGF β1. Therefore, quinolone can potentially be used for the treatment of fibrotic kidney diseases but further studies are required to ascertain this.
Keywords: Quinolone oxizime, Anti-fibrosis, Tubulo-interstitium, Interstitium, Fibroblasts
Methods: Proliferation of renal fibroblasts was determined using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while laser confocal fluorescence microscope was used for immuno-cytochemical studies. Total TGF β1 was determined by enzyme linked immunosorbent assay (ELISA).
Results: Quinolone oxizime decreased the proliferation of renal fibroblasts in a dose-dependent manner (p < 0.05) in vitro. Proliferation of renal fibroblasts was 39, 63, 82, 95, 97 and 99 % on treatment with quinolone oxizime at doses of 10, 8, 6, 4, 2 and 1 μM, respectively, after 48 h. The expression of TGF β1 in the peripheral blood lymphocytes was reduced significantly by quinolone oxizime treatment. In the animal model of renal fibrosis, quinolone oxizime treatment decreased development of lesions, prevented tubular dilation and expansion of interstitium. After 30 days of quinolone oxizime treatment, tubulo-interstitial lesions were completely absent in rats in the 5 mg/kg treatment group. Moreover, quinolone oxizime treatment for 30 days inhibited accumulation of extracellular matrix and prevented renal injury in rats.
Conclusion: These results show that quinolone oxizime exhibits anti-fibrotic effects through targeting the expression of TGF β1. Therefore, quinolone can potentially be used for the treatment of fibrotic kidney diseases but further studies are required to ascertain this.
Keywords: Quinolone oxizime, Anti-fibrosis, Tubulo-interstitium, Interstitium, Fibroblasts