Abstract：
Lithium (Li) is a mood-stabilizing drug. Although one of the potential mechanisms underlying the neuroprotective effects of lithium is related to its antioxidative effect, its mechanisms of action are not fully understood. Herein we aimed to investigate the impact of varied dosages of long-term lithium therapy on oxidative stress parameters in the brains of healthy rats, and on anxiety-like behaviors, and whether any changes in behavior can be attributed to modifications in oxidative stress levels within the brain. Thirty-two adult Wistar albino male rats were randomly assigned to four treatment groups. While the control (C) group was fed with a standard diet, low Li (1.4 g/kg/diet), moderate Li (1.8 g/kg/diet), and high Li (2.2 g/kg/diet) groups were fed with lithium bicarbonate (Li2CO3) for 30 days. Malondialdehyde increased, while superoxide dismutase and catalase levels decreased in the brains of the high Li group animals. In addition, anxiety-like behaviors of animals increased in the high Li group considering fewer entries to and less time spent in the open arms of the elevated plus maze test. Our findings underscore the potential adverse effects of prolonged lithium treatment, especially at doses approaching the upper therapeutic range. The induction of toxicity, manifested through heightened oxidative stress, appears to be a key mechanism contributing to the observed increase in anxiety-like behaviors. Consequently, caution is warranted when considering extended lithium therapy at higher doses, emphasizing the need for further research to delineate the precise mechanisms underlying these effects and to inform safer therapeutic practices.
摘要：
锂（Li）是一种稳定情绪的药物。尽管锂的神经保护作用的潜在机制之一与其抗氧化作用有关，其作用机制尚未完全了解。本研究旨在探讨长期锂治疗不同剂量对健康大鼠大脑氧化应激参数的影响。以及类似焦虑的行为，以及行为的任何变化是否可以归因于大脑内氧化应激水平的改变。将32只成年Wistar白化病雄性大鼠随机分配到四个治疗组。而对照组（C）用标准饮食喂养，低锂（1.4克/千克/饮食），中度Li（1.8g/kg/日），和高Li(2.2g/kg/日粮)组用碳酸氢锂(Li2CO3)喂养30天。丙二醛增多,而高Li组动物大脑中的超氧化物歧化酶和过氧化氢酶水平降低。此外,在高锂组中，动物的焦虑样行为增加，考虑到较少的进入和较少的时间花在高架迷宫测试的张开双臂上。我们的发现强调了长期锂治疗的潜在不利影响，尤其是在接近治疗上限的剂量下。毒性的诱导，表现为增强的氧化应激，似乎是导致观察到的焦虑样行为增加的关键机制。因此,在考虑更高剂量的长期锂治疗时，谨慎是必要的，强调需要进一步研究，以描述这些影响的确切机制，并为更安全的治疗实践提供信息。
