Shvartsur Rachel, Agam Galila, Shnaider Alla, Uzzan Sarit, Nassar Ahmad, Jabarin Adi, Abu-Freha Naim, Meir Karen, Azab Abed N
Department of Nursing, School for Community Health Professions, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Pharmaceutics. 2021 Nov 1;13(11):1827. doi: 10.3390/pharmaceutics13111827.
Despite established efficacy in bipolar disorder patients, lithium (Li) therapy has serious side effects, particularly chronic kidney disease. We examined the safety and behavioral effects of combined chronic low-dose aspirin plus low-dose Li in rats to explore the toxicity and therapeutic potential of this treatment. Rats were fed regular or Li-containing food (0.1% [low-dose, LLD-Li] or 0.2% [standard-dose, STD-Li]) for six weeks. Low-dose aspirin (1 mg/kg) was administered alone or together with Li. Renal function and gastric mucosal integrity were assessed. The effects of the combination treatment were evaluated in depression-like and anxiety-like behavioral models. Co-treatment with aspirin did not alter plasma Li levels. Chronic STD-Li treatment resulted in significant polyuria and polydipsia, elevated blood levels of creatinine and cystatin C, and increased levels of kidney nephrin and podocin-all suggestive of impaired renal function. Aspirin co-treatment significantly damped STD-Li-induced impairments in kidney parameters. There were no gastric ulcers or blood loss in any treatment group. Combined aspirin and LLD-Li resulted in a significant increase in sucrose consumption, and in the time spent in the open arms of an elevated plus-maze compared with the LLD-Li only group, suggestive of antidepressant-like and anxiolytic-like effects, respectively. Thus, we demonstrate that low-dose aspirin mitigated the typical renal side effects of STD-Li dose and enhanced the beneficial behavioral effects of LLD-Li therapy without aggravating its toxicity.
尽管锂（Li）疗法在双相情感障碍患者中已证实具有疗效，但它有严重的副作用，尤其是慢性肾病。我们研究了慢性低剂量阿司匹林联合低剂量Li对大鼠的安全性和行为影响，以探索这种治疗方法的毒性和治疗潜力。大鼠连续六周喂食普通食物或含Li食物（0.1%[低剂量，LLD-Li]或0.2%[标准剂量，STD-Li]）。低剂量阿司匹林（1mg/kg）单独给药或与Li联合给药。评估肾功能和胃黏膜完整性。在抑郁样和焦虑样行为模型中评估联合治疗的效果。阿司匹林联合治疗未改变血浆Li水平。慢性STD-Li治疗导致显著的多尿和多饮，血肌酐和胱抑素C水平升高，以及肾脏nephrin和podocin水平增加，所有这些都提示肾功能受损。阿司匹林联合治疗显著减轻了STD-Li诱导的肾脏参数损伤。任何治疗组均未出现胃溃疡或失血。与仅使用LLD-Li的组相比，阿司匹林与LLD-Li联合使用导致蔗糖消耗量显著增加，以及在高架十字迷宫开放臂中停留的时间显著增加，分别提示有抗抑郁样和抗焦虑样作用。因此，我们证明低剂量阿司匹林减轻了STD-Li剂量典型的肾脏副作用，并增强了LLD-Li治疗的有益行为效果，而不会加重其毒性。
