Chan B S, Seale J P, Duggin G G
Department of Renal Medicine and Toxicology Unit, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Toxicol Lett. 1997 Jan 15;90(1):1-9. doi: 10.1016/s0378-4274(96)03820-9.
Paraquat (PQ)(1,1'-dimethyl-4,4'-bipyridinium) is a toxic herbicidal cation. The renal excretory mechanisms of PQ and its interactions with organic cations and anions were investigated in anaesthetised rats. The renal clearance of PQ was studied in male Wistar rats using inulin as the marker of glomerular filtration rate. The fractional excretion of paraquat (FEpq) decreased from 2.1+/-0.01 to 1.2+/-0.03 as the plasma concentration rose from 0.4+/-0.02 to 21.2+/-1.6 microM. These results demonstrated that the excretion of PQ was greater than glomerular filtration, concentration dependent and saturable, indicating that it was secreted by an active transport system. The excretion of PQ was dependent predominantly on the glomerular filtration rate with a small secretory component (Km = 8.5+/-3.1 microM, Vmax = 114+/-19 nmol/kg per min). The clearance of PQ was not inhibited by high doses of cimetidine, or p-aminohippurate. However, quinine (P = 0.001) and N-methylnicotinamide (NMN) (P = 0.03) reduced the FEpq, suggesting that they share a similar cation transport system with PQ. In summary, PQ is actively secreted by the rat kidney via a cation transport system.
百草枯（PQ）（1,1'-二甲基-4,4'-联吡啶鎓）是一种有毒的除草阳离子。在麻醉大鼠中研究了PQ的肾脏排泄机制及其与有机阳离子和阴离子的相互作用。以菊粉作为肾小球滤过率的标志物，在雄性Wistar大鼠中研究了PQ的肾脏清除率。随着血浆浓度从0.4±0.02微摩尔/升升至21.2±1.6微摩尔/升，百草枯的分数排泄（FEpq）从2.1±0.01降至1.2±0.03。这些结果表明，PQ的排泄大于肾小球滤过，呈浓度依赖性且可饱和，表明它是由主动转运系统分泌的。PQ的排泄主要取决于肾小球滤过率，并有少量分泌成分（Km = 8.5±3.1微摩尔/升，Vmax = 114±19纳摩尔/千克每分钟）。高剂量的西咪替丁或对氨基马尿酸不会抑制PQ的清除率。然而，奎宁（P = 0.001）和N-甲基烟酰胺（NMN）（P = 0.03）降低了FEpq，表明它们与PQ共用一个类似的阳离子转运系统。总之，PQ通过阳离子转运系统由大鼠肾脏主动分泌。
