Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats.
Rachel ShvartsurGalila AgamAlla ShnaiderSarit UzzanAhmad NassarAdi JabarinNaim Abu FrehaKaren MeirAbed N AzabPublished in: Pharmaceutics (2021)
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.
Keyphrases
- low dose
- ion batteries
- high dose
- chronic kidney disease
- bipolar disorder
- solid state
- end stage renal disease
- cardiovascular events
- stem cells
- type diabetes
- antiplatelet therapy
- metabolic syndrome
- atrial fibrillation
- oxidative stress
- prognostic factors
- mesenchymal stem cells
- combination therapy
- coronary artery disease
- climate change
- cell therapy
- preterm birth
- endothelial cells
- percutaneous coronary intervention
- acute coronary syndrome