Albeit having negative impacts on human health, Li is not an uncommon component of many medicines including treatment for bipolar disorder (Gitlin, 2016; Duvall & Gallicchio, 2017). Side effects of patients taking these medicine include kidney problems and dizziness similar to those discussed in the previous blogs, further proving the impacts Li have on human health (Gitlin, 2016; Duvall & Gallicchio, 2017).
However, currently, most studies about the negative impacts Li has on humans revolve around the kidney and little is known about its impacts on the cardiovascular system (Shen et al., 2020). Besides cardiovascular diseases caused by kidney diseases, Shen et al. (2020) found that Li significantly constrained the proliferation of cardiomyocytes, the ‘cell responsible for the contraction of the heart’ (Keepers et al., 2020). Li was also found to encourage cell apoptosis (Shen et al., 2020) (Figure 1).
Apoptosis: A type of cell death in which a series of molecular steps in a cell lead to its death. This is one method the body uses to get rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death. – National Cancer Institute, n.d.
Figure 1: Apoptosis VS Necrosis, ways a cell dies (CUSABIO TECHNOLOGY LLC, n.d.)
Shen et al. (2020) tested the impact of Li on AC16 Human Cardiomyocyte Cell Line propagated using DMEM High Glucose (Dulbecco’s Modified Eagle Medium) at different concentrations.
AC16 is a proliferating human cardiomyocyte cell line that was derived from the fusion of primary cells from adult human ventricular heart tissues with SV40 transformed, uridine auxotroph human fibroblasts, devoid of mitochondrial DNA… AC-16 can be used to address questions of cardiac biology at the cellular and molecular levels. – Merck KGaA, n.d.
Cell Proliferation
LiCl/Li2SO4 at 0.2 mmol/L, 1 mmol/L, 5 mmol/L or 25 mmol/L were used over a period of 2 days on the AC16 Human Cardiomyocyte cells (Shen et al., 2020). After 2 days, Shen et al. (2020) discovered that the growth of cells that were exposed to 5 mmol/L and 25 mmol/L of LiCl was notably inhibited (Figure 2).
Figure 2: Proliferation of AC16 cells measured in luminescent assay and CCK-8 assay (Shen et al., 2020)
To determine if growth inhibition was due to Cl instead of Li, Shen et al. (2020) added NaCl to the study and found no significant change when NaCl was added. Additionally, the growth of cells that were exposed to 2.5 mmol/L and 12.5 mmol/L of Li2SO4 was also evidently inhibited (Shen et al., 2020).
Cell Apoptosis
To study cell apoptosis, Annexin V‐FITC/PI apoptosis assay is used(Shen et al., 2020; Rieger et al., 2011).
The Annexin V/PI protocol is a commonly used approach for studying apoptotic cells. PI is used more often than other nuclear stains because it is economical, stable and a good indicator of cell viability, based on its capacity to exclude dye in living cells. – Rieger et al., 2011
After 2 days, cells treated with 5 mmol/L LiCl and 2.5 mmol/L Li2SO4 observed a significant increase in cell apoptosis compared to uncontaminated cells (Shen et al., 2020) (Figure 3).
Figure 3: Cell apoptosis of AC16 cells (Shen et al., 2020)
Therefore, besides the known effects Li has on the kidney and liver, exposure and intake of high concentrations of Li can potentially have a deadly effect on the heart and the cardiovascular system. In the next blog, I will explore how we may be more vulnerable to taking in high concentrations of Li today as compared to the past.
Reference List:
CUSABIO TECHNOLOGY LLC. (n.d.). Get an Overview of Cell Death- CUSABIO. https://www.cusabio.com/cytokines/Cell-Death.html
Duvall, A. E., & Gallicchio, V. S. (2017). Lithium Treatment in Clinical Medicine: History, Current Status and Future Use. Journal of Cell Science &Amp; Therapy, 08(03). https://doi.org/10.4172/2157-7013.1000270
Gitlin, M. (2016). Lithium side effects and toxicity: prevalence and management strategies. International Journal of Bipolar Disorders, 4(1). https://doi.org/10.1186/s40345-016-0068-y
Keepers, B., Liu, J., & Qian, L. (2020). What’s in a cardiomyocyte – And how do we make one through reprogramming? Biochimica Et Biophysica Acta (BBA) – Molecular Cell Research, 1867(3), 118464. https://doi.org/10.1016/j.bbamcr.2019.03.011
Merck KGaA. (n.d.). AC16 Human Cardiomyocyte Cell Line. In Merck KGaA. https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/150/525/20228073-scc109.pdf
National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/apoptosis
Rieger, A. M., Nelson, K. L., Konowalchuk, J. D., & Barreda, D. R. (2011). Modified Annexin V/Propidium Iodide Apoptosis Assay For Accurate Assessment of Cell Death. Journal of Visualized Experiments, 50. https://doi.org/10.3791/2597
Shen, J., Li, X., Shi, X., Wang, W., Zhou, H., Wu, J., Wang, X., & Li, J. (2020). The toxicity of lithium to human cardiomyocytes. Environmental Sciences Europe, 32(1). https://doi.org/10.1186/s12302-020-00333-6