Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats

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...

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Autores principales:	Rachel Shvartsur, Galila Agam, Alla Shnaider, Sarit Uzzan, Ahmad Nassar, Adi Jabarin, Naim Abu-Freha, Karen Meir, Abed N. Azab
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	aspirin bipolar disorder inflammation lithium nephrotoxicity Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/b739ee24ca384418881f4b9a5ad6312a
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spelling	oai:doaj.org-article:b739ee24ca384418881f4b9a5ad6312a2021-11-25T18:40:58ZSafety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats10.3390/pharmaceutics131118271999-4923https://doaj.org/article/b739ee24ca384418881f4b9a5ad6312a2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1827https://doaj.org/toc/1999-4923Despite 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.Rachel ShvartsurGalila AgamAlla ShnaiderSarit UzzanAhmad NassarAdi JabarinNaim Abu-FrehaKaren MeirAbed N. AzabMDPI AGarticleaspirinbipolar disorderinflammationlithiumnephrotoxicityPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1827, p 1827 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aspirin bipolar disorder inflammation lithium nephrotoxicity Pharmacy and materia medica RS1-441
spellingShingle	aspirin bipolar disorder inflammation lithium nephrotoxicity Pharmacy and materia medica RS1-441 Rachel Shvartsur Galila Agam Alla Shnaider Sarit Uzzan Ahmad Nassar Adi Jabarin Naim Abu-Freha Karen Meir Abed N. Azab Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats
description	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.
format	article
author	Rachel Shvartsur Galila Agam Alla Shnaider Sarit Uzzan Ahmad Nassar Adi Jabarin Naim Abu-Freha Karen Meir Abed N. Azab
author_facet	Rachel Shvartsur Galila Agam Alla Shnaider Sarit Uzzan Ahmad Nassar Adi Jabarin Naim Abu-Freha Karen Meir Abed N. Azab
author_sort	Rachel Shvartsur
title	Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats
title_short	Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats
title_full	Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats
title_fullStr	Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats
title_full_unstemmed	Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats
title_sort	safety and efficacy of combined low-dose lithium and low-dose aspirin: a pharmacological and behavioral proof-of-concept study in rats
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b739ee24ca384418881f4b9a5ad6312a
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Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats

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