Lithium Treatment Induces Cardiac Dysfunction in Mice

Abstract

Lithium (Li) salts are commonly used as medications for bipolar disorders. In addition to its therapeutic value, Li is also being increasingly used as a battery component in modern electronic devices. Concerns about its toxicity and negative impact on the heart have recently been raised. We investigated the effects of long-term Li treatment on the heart, liver, and kidney in mice. Sixteen C57BL/6J mice were randomly assigned to receive oral administration of Li carbonate (n = 8) or act as a control group (n = 8) for 12 weeks. We evaluated the cardiac electrical activity, morphology and function, and pathways contributing to remodelling. We assessed the multi-organ toxicity using histopathology techniques in the heart, liver, and kidney. Our findings suggest that mice receiving Li had impaired systolic function and ventricular repolarisation and were more susceptible to arrhythmias under adrenergic stimulation. The Li treatment caused an increase in the cardiomyocytes’ size, the modulation of the extracellular signal-regulated kinase (ERK) pathway, along with some minor tissue damage. Our findings revealed a cardiotoxic effect of Li at therapeutic dosage, along with some histopathological alterations in the liver and kidney. In addition, our study suggests that our model could be used to test potential treatments for Li-induced cardiotoxicity.

Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs

“…This may result in arrhythmias, fetal cardiac malformations, and reduced contractile responses to adrenergic signaling ( Mehta and Vannozzi, 2017 ; Patorno et al, 2017 ; Moradi et al, 2019 ; Hamstra et al, 2023 ). Animal studies have shown that treatment with lithium carbonate at a dose of 45 mg/kg for 12 weeks causes myocardial histopathologic damage ( L'Abbate et al, 2023 ). Therefore, electrocardiograms should be monitored in patients undergoing long-term lithium therapy due to the associated prolonged QTc intervals ( Mamiya et al, 2005 ).…”

Impact of chronic lithium treatment on brain oxidative stress and anxiety-like behaviors in rats: Dose-dependent effects

“…Although neuroprotective/ neurotrophic effects of lithium have been demonstrated previously (Forlenza et al 2014;Roux and Dosseto 2017), there have been reports of its neurotoxicity occurring even at therapeutic doses by altering oxidative stress status in the brain (Bhalla et al 2007;Mezni et al 2017). Various studies also suggested lithium may have adverse effects such as renal impairment, cardiotoxicity, cytotoxicity in the liver, and hypothyroidism (Eskandari et al 2012;Nciri et al 2012;Shine et al 2015;Abdel Hamid et al 2020;L' Abbate et al 2023).…”