RESUMO
The body is exposed to various organic anions,so it is the best way to remove the toxic substances in the body quickly and effectively.Cross epithelial active transport mediated by organic anion transporter is the rate limiting process.Renal secretion and re-absorption of a variety of endogenous and exogenous organic anions are occurred in the proximal tubular epithelial cells of the organic anion transporter family.The expression of organic anion transporter-1 (OAT1) in proximal tubular epithelial cells plays an important role in the introduction of organic anion into the renal tubular epithelial cells.This article reviewed the renal expression,the substrate and the polymorphism of the organic anion transport protein OAT1,the renal toxicity of adefovir dipivoxil,the interaction between organic anion transporters and drug,and the influence of the renal toxicity on the renal toxicity of adefovir dipivoxil.
RESUMO
Objective To investigate the role of rat organic anion transporter 1 (OAT1, SLC22A6) in the renal cellular uptake of AA Ⅰ and its impact on cellular toxicity. Methods HEK-293 cells were transfeeted with rat OAT1 cDNA or empty vectors. The over-expression of rOAT1 was confirmed by Western blot analysis and its activity was validated by using para-aminohippurate (PAH) as a probe. Cellular apoptosis was examined by flow cytometery using propodium iodode (PI) and annexin V-FITC staining. Results Concentration-and time-dependent intracellular accumulation of AA Ⅰ was observed in rOATl-transfected HEK-293 cells. After treatment with AA Ⅰ at the concentrations of 40 mg/L, 80 mg/L, 120 mg/L and 160 mg/L,respectively, for 45 min, the intracellular concentrations of AA Ⅰ in rOAT1-transfected HEK-293 cells were higher than those in controls (P<0.05). After treatment with AA Ⅰ (120 mg/L for 30 min, 60 min, 90 min and 120 min, respectively, the intracellular concentrations of AA Ⅰ in rOAT1-transfected HEK-293 cells were higher than those in controls (P<0.05). PAH significantly reduced the intracellular accumulations of AA Ⅰ in rOAT1-transfected HEK-293 cells. After treatment with AA Ⅰ at the concentrations of 40 mg/L, 80 mg/L, 120 mg/L and 160 mg/L respectively for 35 min, the intracellular accumulations of AA Ⅰ in rOAT1-transfected HEK-293 cells that treated with PAH were lower than those that were not treated by PAH. Cellular apoptosis and caspase-3 expression in rOAT1-transfeeted HEK-293 cells were significantly up-regnlated as compared to controls (P<0.05). Conclusion rOAT1 is involved in the cellular uptake of AA Ⅰ which leads to increased epithelial apoptosis. Further studies are suggested to investigate the role of human OAT in the disposition of AA and its toxicological consequences.