The relative toxicity of 48 anilines using the Tetrahymena pyriformis population growth characteristics IGC50 （concentration causing 50% growth inhibition）, available in the literature, was studied. At first, the en...The relative toxicity of 48 anilines using the Tetrahymena pyriformis population growth characteristics IGC50 （concentration causing 50% growth inhibition）, available in the literature, was studied. At first, the entire data set was randomly split into a training set （31 chemicals） used to establish the QSAR model, and a test set （17 chemicals） for statistical external validation. A biparametric model was developed using, as independent variables, 3D theoretical descriptors derived from DRAGON software. The GA-MLR （genetic algorithm variable subset selection） procedure was performed on the trainingset by the software mobydigs using the OLS （ordinary least squares） regression method, and GA（genetic algorithm）-VSS（variable subset selection） by maximising the cross-validated explained variance （Q^2Loo）＇ The obtained model was examined for robustness （Q^2LOOcross-validation, Y-scrambling） and predictive ability through both internal （Q^2LM0, bootstrap） and external validation （Q^2ext） methods. Descriptors included in the QSAR model indicated that log/GC^-150 value was related to molecular size and shape, and interaction of molecule with its surrounding medium or its target. Moreover, the applicability domain of the model was discussed.展开更多
Objective To investigate the inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine A (CsA)-induced chronic nephrotoxicity.Methods Four groups of rats with CsA-in...Objective To investigate the inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine A (CsA)-induced chronic nephrotoxicity.Methods Four groups of rats with CsA-induced chronic nephrotoxicity were respectively treated with vehicle olive oil, tea polyphenols, CsA and tea polyphenols plus CsA. At the end of the 28th day of treatment, 24 hours urine and blood samples were obtained, and the animals were then sacrificed. The serum and urine samples were analysed for creatinine clearance, and kidney tissue was used for pathologic analysis of renal tubular injury and interstitial fibrosis. The TUNEL assay, apoptosis-related enzyme caspase-3 mRNA detected by RT-PCR, and its enzymatic activity were analysed for the possible detections of cell apoptosis.Results CsA-treated rats displayed increased apoptosis of the tubular and interstitial cells, in comparison with vehicle-treated controls (18. 3±4. 6 vs 4. 8±1.3 cells/mm2, P < 0. 05 ) . In comparision with animals treated by CsA, animals treated with CsA plus tea polyphenols demonstrated significantly improved levels of creatinine clearance (0. 12 ±0. 03 vs 0. 22±0. 02 ml ·min-1·100g-1 body weight, P < 0. 05), tubular injury (2. 29 ±0. 43 vs 1. 42±0. 26, P < 0. 05), and interstitial fibrosis (2. 83±0. 20 vs 1. 46±0. 19, P <0. 05), and showed a statistically significant decrease in tubular and interstitial cell apoptosis (18. 3±4. 6 vs 7. 7±2.1 cells/mm2, P<0. 05). The expression of caspase-3 mRNA and caspase-3 activity was significantly higher in the CsA-treated group than that of the CsA plus tea polyphenols (TP)-treated group (P<0. 05).Conclusion These results suggested that tea polyphenols significantly inhibits apoptosis of the tubular and interstitial cells in rats with cyclosporine-induced chronic nephrotoxicity, and that tea polyphenols may be useful to prevent CsA-associated kidney toxicity.展开更多
文摘The relative toxicity of 48 anilines using the Tetrahymena pyriformis population growth characteristics IGC50 （concentration causing 50% growth inhibition）, available in the literature, was studied. At first, the entire data set was randomly split into a training set （31 chemicals） used to establish the QSAR model, and a test set （17 chemicals） for statistical external validation. A biparametric model was developed using, as independent variables, 3D theoretical descriptors derived from DRAGON software. The GA-MLR （genetic algorithm variable subset selection） procedure was performed on the trainingset by the software mobydigs using the OLS （ordinary least squares） regression method, and GA（genetic algorithm）-VSS（variable subset selection） by maximising the cross-validated explained variance （Q^2Loo）＇ The obtained model was examined for robustness （Q^2LOOcross-validation, Y-scrambling） and predictive ability through both internal （Q^2LM0, bootstrap） and external validation （Q^2ext） methods. Descriptors included in the QSAR model indicated that log/GC^-150 value was related to molecular size and shape, and interaction of molecule with its surrounding medium or its target. Moreover, the applicability domain of the model was discussed.
基金This study was supported by the National Natural Science Foundation of China (No. 30170899).
文摘Objective To investigate the inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine A (CsA)-induced chronic nephrotoxicity.Methods Four groups of rats with CsA-induced chronic nephrotoxicity were respectively treated with vehicle olive oil, tea polyphenols, CsA and tea polyphenols plus CsA. At the end of the 28th day of treatment, 24 hours urine and blood samples were obtained, and the animals were then sacrificed. The serum and urine samples were analysed for creatinine clearance, and kidney tissue was used for pathologic analysis of renal tubular injury and interstitial fibrosis. The TUNEL assay, apoptosis-related enzyme caspase-3 mRNA detected by RT-PCR, and its enzymatic activity were analysed for the possible detections of cell apoptosis.Results CsA-treated rats displayed increased apoptosis of the tubular and interstitial cells, in comparison with vehicle-treated controls (18. 3±4. 6 vs 4. 8±1.3 cells/mm2, P < 0. 05 ) . In comparision with animals treated by CsA, animals treated with CsA plus tea polyphenols demonstrated significantly improved levels of creatinine clearance (0. 12 ±0. 03 vs 0. 22±0. 02 ml ·min-1·100g-1 body weight, P < 0. 05), tubular injury (2. 29 ±0. 43 vs 1. 42±0. 26, P < 0. 05), and interstitial fibrosis (2. 83±0. 20 vs 1. 46±0. 19, P <0. 05), and showed a statistically significant decrease in tubular and interstitial cell apoptosis (18. 3±4. 6 vs 7. 7±2.1 cells/mm2, P<0. 05). The expression of caspase-3 mRNA and caspase-3 activity was significantly higher in the CsA-treated group than that of the CsA plus tea polyphenols (TP)-treated group (P<0. 05).Conclusion These results suggested that tea polyphenols significantly inhibits apoptosis of the tubular and interstitial cells in rats with cyclosporine-induced chronic nephrotoxicity, and that tea polyphenols may be useful to prevent CsA-associated kidney toxicity.
