Department of Medical Chemistry, Medical University of Gdańsk, Dębinki 1, PL 80-211 Gdańsk, Poland.
Pharmacol Rep. 2011;63(2):441-7. doi: 10.1016/s1734-1140(11)70510-2.
Fluoxetine (Flux) is a fluorine-containing drug that selectively inhibits serotonin reuptake. It is widely prescribed as a treatment for depression disorders. Hepatic side effects have been reported during Flux therapy. These reports led us to investigate the involvement of oxidative stress mechanisms in liver injury caused by Flux. It has been shown that exposure to fluoride (F(-)) induces excessive production of free radicals and affects the antioxidant defense system. Based on this knowledge, we examined the F(-) concentration in serum and urine during administration of Flux. In our study, the effects of one month of Flux treatment on lipid and protein peroxidation, the concentration of uric acid in the liver and the activity of transaminases and transferases in the serum were investigated in rats. Eighteen adult male Wistar rats were divided into three equal groups of six animals each: (I) controls who drank tap water and received 1 ml of tap water intragastrically; (II) animals that received 8 mg Flux/kg bw/day intragastrically; and (III) animals that received 24 mg Flux/kg bw/day intragastrically. Flux treatment increased of the levels of carbonyl groups, thiobarbituric acid reactive species (TBARS) and the uric acid content in the liver. The activities of alanine transaminase (ALT), aspartate transaminase (AST) and glutathione-S transferase (GST) increased in the serum of the treated groups. The Flux levels in the plasma of the treated rats increased significantly in a dose-dependent manner. We observed no changes in the concentration of fluoride in either the serum or the urine of treated rats compared to the control group. In conclusion, our study indicates that Flux induces liver damage and mediates free radical reactions. Our data also indicate that Flux does not release F(-) during metabolism and does not affect physiological levels of F(-) in the serum or urine.
氟西汀（Flux）是一种含氟药物，选择性地抑制血清素再摄取。它被广泛开处方用于治疗抑郁症。在 Flux 治疗期间报告了肝副作用。这些报告促使我们研究氧化应激机制在 Flux 引起的肝损伤中的作用。已经表明，暴露于氟化物（F（-））会诱导自由基的过度产生，并影响抗氧化防御系统。基于这一知识，我们在 Flux 给药期间检查了血清和尿液中的 F（-）浓度。在我们的研究中，研究了 Flux 治疗一个月对大鼠肝脂质和蛋白质过氧化、尿酸浓度以及血清中转氨酶和转移酶活性的影响。将 18 只成年雄性 Wistar 大鼠分为三组，每组 6 只：（I）对照组，饮用自来水并口服 1ml 自来水；（II）口服 8mg Flux/kg bw/天的动物；（III）口服 24mg Flux/kg bw/天的动物。Flux 处理增加了肝羰基、硫代巴比妥酸反应性物质（TBARS）和尿酸含量。血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和谷胱甘肽-S-转移酶（GST）的活性在处理组中增加。处理大鼠血浆中的 Flux 水平呈剂量依赖性显著增加。与对照组相比，我们未观察到处理组大鼠血清或尿液中氟化物浓度的变化。总之，我们的研究表明 Flux 诱导肝损伤并介导自由基反应。我们的数据还表明，Flux 在代谢过程中不会释放 F（-），也不会影响血清或尿液中 F（-）的生理水平。
