Fairshter R D, Vaziri N D, Crosby S A, Rosario L, Toohey J A, Ulich T R
Department of Medicine and Pathology, University of California, Irvine, Orange 92668.
Toxicology. 1988 Jun;50(1):47-56. doi: 10.1016/0300-483x(88)90120-5.
In a previous study, administration of the hydroxyl radical scavenger, dimethylthiourea (DMTU), and paraquat was associated with higher mortality in rats than was paraquat alone. In the present study, the possibility was evaluated that administration of DMTU increased plasma paraquat levels. Plasma paraquat concentrations were measured in Sprague-Dawley rats 1, 2, 4, 8 and 24 h after intraperitoneal (i.p.) injection of 29 mg paraquat cation/kg body wt. Another group of rats was treated identically except that they received i.p. injections of DMTU before injections of paraquat. Administration of DMTU was associated with increased plasma paraquat concentration (P less than 0.01). Pharmacokinetic analyses indicated that, compared to rats receiving paraquat alone, rats given paraquat and DMTU showed: (1) greater area under the paraquat concentration time-curve; (2) lower total body paraquat clearance; and (3) smaller apparent volume of distribution. Plasma biochemical studies indicated that paraquat caused hyperglycemia as well as an early reduction (compared to controls) in hepatic enzymes. We conclude that: (1) DMTU administration is associated with increased plasma paraquat concentrations; and (2) impaired synthesis or inhibition of release of hepatic proteins may be an early effect of paraquat.
在先前的一项研究中，给大鼠同时施用羟自由基清除剂二甲基硫脲（DMTU）和百草枯，其死亡率高于单独施用百草枯的大鼠。在本研究中，评估了施用DMTU会增加血浆百草枯水平的可能性。在腹腔注射29 mg百草枯阳离子/ kg体重后的1、2、4、8和24小时，测定Sprague-Dawley大鼠的血浆百草枯浓度。另一组大鼠的处理方式相同，只是在注射百草枯之前先腹腔注射DMTU。施用DMTU与血浆百草枯浓度升高有关（P<0.01）。药代动力学分析表明，与单独接受百草枯的大鼠相比，接受百草枯和DMTU的大鼠表现为：（1）百草枯浓度-时间曲线下面积更大；（2）全身百草枯清除率更低；（3）表观分布容积更小。血浆生化研究表明，百草枯会导致高血糖以及肝酶早期降低（与对照组相比）。我们得出以下结论：（1）施用DMTU与血浆百草枯浓度升高有关；（2）肝蛋白合成受损或释放受抑制可能是百草枯的早期作用。
