Department of Medical Chemistry, Medical University of Gdansk, Gdańsk, Poland.
Pharmacol Rep. 2012;64(4):902-11. doi: 10.1016/s1734-1140(12)70885-x.
This study was undertaken to investigate, the effect of 6 weeks treatment with acetaminophen (AAP) and fluoride (F), administered either separately or together, on nitric oxide generation, lipid and protein peroxidation, total antioxidant status and level of reduced glutathione in the liver and kidney of male and female Wistar Han rats. Also, the influence of AAP on F excretion in urine was determined.
Thirty adult male and female rats were divided into five equal groups of six each: (I) controls drinking tap water; (II) controls drinking tap water and receiving 1 ml of tap water intragastrically; (III) animals receiving 12 mg F/L in drinking water; (IV) animals receiving 150 mg AAP /kg b.w./day; (V) animals receiving 12 mg F/L in drinking water and 150 mg AAP /kg b.w./day.
F and AAP given separately and both together enhanced oxidative and nitrosative stress in investigated tissues. No gender differences were observed in oxidative/nitrosative stress parameters during treatment with F and/or AAP. Interestingly, the combined exposure to F and AAP resulted in an enhancement of oxidative/nitrosative stress in kidney of male and female rats compared to the group treated separately with F and AAP. No additive effect in the measured parameters in the liver during co-exposure to both xenobiotics was noticed.
As expected, the urinary F excretion increased in an exposure time-dependent manner in rats receiving F or a combination of F and AAP. The study also showed that AAP significantly decreased urinary F.
本研究旨在探讨 6 周乙酰氨基酚（AAP）和氟化物（F）单独或联合治疗对雄性和雌性 Wistar Han 大鼠肝、肾中一氧化氮生成、脂质和蛋白质过氧化、总抗氧化状态和还原型谷胱甘肽水平的影响。此外，还确定了 AAP 对尿液中 F 排泄的影响。
30 只成年雄性和雌性大鼠分为 5 组，每组 6 只：（I）对照组饮用自来水；（II）对照组饮用自来水并灌胃 1ml 自来水；（III）动物饮用含 12mg F/L 的水；（IV）动物给予 150mg/kg b.w./天的 AAP；（V）动物饮用含 12mg F/L 的水和 150mg/kg b.w./天的 AAP。
F 和 AAP 单独和联合使用均增强了所研究组织中的氧化和硝化应激。在 F 和/或 AAP 治疗期间，未观察到氧化/硝化应激参数在性别之间存在差异。有趣的是，与单独用 F 和 AAP 治疗的组相比，联合暴露于 F 和 AAP 导致雄性和雌性大鼠肾脏中的氧化/硝化应激增强。在同时暴露于两种外来物质时，肝脏中测量的参数没有观察到相加效应。
正如预期的那样，接受 F 或 F 和 AAP 联合治疗的大鼠尿液中 F 的排泄量随暴露时间的增加而增加。研究还表明，AAP 显著降低了尿液中的 F。
