Category Archives: Impact on Humans and Animals

Benefits of naturally occurring Lithium in water

Having discussed the negative impact Li pollution has on biodiversity, I would like to explore the benefits natural Li, Li in small amounts can have for biodiversity in this blog. Like most naturally occurring things (e.g. greenhouse effect), Li plays an important role in the healthy growth and development of humans and animals in small amounts. Li occurs naturally in small amounts in groundwater and soil (Memon et al., 2020). Although only found in small concentrations averaging between 3.8 and 46.3 μg/L (0.0005–0.0067 mmol/L) (Araya et al., 2022), Li positively impacts the health of people. 

Figure 1

The benefits of naturally occurring Li include:

1. Reduces rates of suicide

Drinking water with naturally occurring Li has been found to improve the mental health of people (Memon et al., 2020). Over the years, many studies have been conducted to find the relationship between different concentrations of Li and suicide rates (Memon et al., 2020; Araya et al., 2022). Although little correlation has been found in concentrations below 30.7 μg/L (0.0044 mmol/L) in drinking water, a much stronger correlation was found between Li and suicide rate at a higher concentration from 32.9 μg/L (0.0047 mmol/L) (Araya et al., 2022). Generally, among the areas studied, areas with a higher natural concentration of Li also recorded lower rates of suicide (Forlenza et al., 2012) (Figure 2). 

Figure 2: Reduce suicide levels with an increase in Li levels (Ohgami et al., 2009)

2. Mood stabilising effects

Apart from reducing rates of suicide, Li have mood stabilisation effects, independent of its anti-suicidal effect (Memon et al., 2020). This is also why despite having negative health impacts when taken in at above natural concentrations, Li continues to be used in bipolar treatment and medicine to stabilise the mood swings of patients (Forlenza et al., 2012). 

3. Neuroprotective effects

Additionally, Li can improve a person’s cognitive function (Neves et al., 2020). Despite only being present naturally, in small amounts, Kessing et al. (2017) found that water with higher concentrations of Li significantly reduced dementia in Denmark. However, when used in the treatment of neurological diseases such as Alzheimer’s disease often requires a higher than the natural concentration of Li of up to 300 µg/day (Neves et al., 2020).

4. Reduces inflammation

Finally, Li is also able to reduce inflammation thanks to its ability to inhibit glycogen synthase kinase-3 (GSK3) (Beurel & Jope, 2014).

GSK3 promotes the production of inflammatory molecules and cell migration, which together make GSK3 a powerful regulator of inflammation. – Jope et al., 2007

While naturally occurring Li benefits humans, the rapid increase in Li pollution can result in Li concentration soaring exponentially in coming years if few related regulations and policies are passed and enforced. The impacts of Li in nature at a much higher concentration will no longer be just beneficial and adverse health impacts discussed in previous blogs will arise, further straining the global health system. 

 

Reference List

Araya, P. E., Martínez, C., & Barros, J. (2022). Lithium in Drinking Water as a Public Policy for Suicide Prevention: Relevance and Considerations. Frontiers in Public Health, 10. https://doi.org/10.3389/fpubh.2022.805774 

Beurel, E., & Jope, R. S. (2014). Inflammation and lithium: clues to mechanisms contributing to suicide-linked traits. Translational Psychiatry, 4(12), e488. https://doi.org/10.1038/tp.2014.129 

Forlenza, O. V., De Paula, V. S., Machado-Vieira, R., Diniz, B. S., & Gattaz, W. F. (2012). Does Lithium Prevent Alzheimerʼs Disease? Drugs & Aging, 29(5), 335–342. https://doi.org/10.2165/11599180-000000000-00000 

Jope, R. S., Yuskaitis, C. J., & Beurel, E. (2007). Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics. Neurochemical Research, 32(4–5), 577–595. https://doi.org/10.1007/s11064-006-9128-5 

Kessing, L. V., Gerds, T. A., Knudsen, N. N., Jørgensen, L., Kristiansen, S., Voutchkova, D. D., Ernstsen, V., Hansen, B., Andersen, P. K., & Ersbøll, A. K. (2017). Association of Lithium in Drinking Water With the Incidence of Dementia. JAMA Psychiatry, 74(10), 1005. https://doi.org/10.1001/jamapsychiatry.2017.2362 

Memon, A., Rogers, I., Fitzsimmons, S. M. D. D., Carter, B., Strawbridge, R., Hidalgo-Mazzei, D., & Young, A. H. (2020). Association between naturally occurring lithium in drinking water and suicide rates: systematic review and meta-analysis of ecological studies. British Journal of Psychiatry, 217(6), 667–678. https://doi.org/10.1192/bjp.2020.128 

Neves, M. G. P. M. S., Marques, J. C., & Eggenkamp, H. G. (2020). Lithium in Portuguese Bottled Natural Mineral Waters—Potential for Health Benefits? International Journal of Environmental Research and Public Health, 17(22), 8369. https://doi.org/10.3390/ijerph17228369 

Ohgami, H., Terao, T., Shiotsuki, I., Ishii, N., & Iwata, N. (2009). Lithium levels in drinking water and risk of suicide. British Journal of Psychiatry, 194(5), 464–465. https://doi.org/10.1192/bjp.bp.108.055798

Impacts of Lithium Pollution on Humans and Animals Part 3

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

Impacts of Lithium Pollution on Humans and Animals Part 2

Continuing from the previous blog, I will continue discussing the impacts Li has (Nciri et al., 2011). 

As exposure to Li decreased chemical and biological functions, particularly in the kidneys and liver, there will be an increase in the risk of diseases (Nciri et al., 2011). Given the similar physiology, organs and body plans, rats often suffer similar diseases as humans (Glass, 2016). Therefore understanding the possible diseases rats can suffer from due to exposure to Li is very beneficial to have a grasp of the possible diseases humans might suffer from when exposed to Li pollution for extended periods

Figure 1: (American Kidney Fund, 2021)

Diseases that may arise include

1. Chronic kidney disease (CKD)

The probability of developing chronic kidney disease increases exponentially due to damage to renal tissue which is caused by prolonged oxidative stress as mentioned in the previous blog (HealthMatters.io, n.d.; American Kidney Fund, 2021). 

CKD reduces the production of the hormone erythropoietin in the kidneys (Laminate Medical, 2017). Hormone erythropoietin is essential to the body as it protects and stimulates the production of red blood cells (Schoener & Borger, 2022). Hence, CKD, especially in people in the last stage of the disease, often results in anemia which can lead to tiredness, dizziness and dyspnea (shortness of breath) (Laminate Medical, 2017). Left untreated, anemia can lead to organ and heart failure (Laminate Medical, 2017). 

2. Cardiovascular diseases 

Besides anemia, CKD often leads to cardiovascular diseases (Pellegrino et al., 2019). A weaker kidney will put more stress on the heart as more energy is needed to bring blood to the kidney (Centers for Disease Control and Prevention, 2022). Additionally, CKD can alter the blood pressure of patients which will lead to heart disease (Centers for Disease Control and Prevention, 2022). 

CKD can also result in the build-up of salt and fluid which will damage blood vessels and cause atherosclerosis (building up of substances along artery walls) (Laminate Medical, 2017; Mayo Clinic, n.d.). 

The build-up of urea in the body, mentioned in the previous blog, results in toxic reactions and causes inflammation of the pericardium, an important sac around the heart that protects and surrounds the heart (Laminate Medical, 2017; Cleveland Clinic, 2022).

3. Cancer

CKD at the later stages often leads to kidney cancer (National Kidney Foundation, n.d.). National Kidney Foundation (n.d.), observed that people who suffer from end-stage CKD are around 5 times as likely to get kidney cancer compared to people with a healthy kidney. 

Kidney cancer occurs when kidney cell mutates and multiply forming a tumour (Mayo Clinic, 2021). Without prompt treatment, the cancer cell can spread to other parts of the body and may lead to other cancer such as Thyroid cancer and Prostate cancer (American Cancer Society, 2020). 

4. Parkinson’s disease and Alzheimer’s disease 

Li pollution leading to CKD can result in Parkinson’s disease among patients (Nciri et al., 2011). Apart from cardiovascular diseases, CKD can result lead to neurological complications (Meléndez-Flores & Estrada-Bellmann, 2020). Meléndez-Flores & Estrada-Bellmann (2020) suggest that the decrease in cognitive functions will result in Parkinson’s disease which can eventually lead to dementia, Alzheimer’s disease and other neural disorders (Nciri et al., 2011; Meléndez-Flores & Estrada-Bellmann, 2020).

 

As the experiment on lab rats only lasted for a month, further impacts of prolonged exposure to Li are not studied. Should Li pollution become significant in water bodies and food chains in the near future, exposure to Li will stay for a much longer period of time if no active measures are taken to reduce concentrations of Li in the environment. Other parts besides the Kidney and Liver may likely be significantly impacted as the length of exposure increases, leading to a range of other diseases. Additionally, Li at concentrations above 2 g/kg of food was not analysed and hence other possible impacts the higher concentration of Li has on animals and humans have yet to be discovered (Nciri et al., 2011). 

 

Reference List: 

American Cancer Society. (2020, June 9). Living as a Kidney Cancer Survivor. https://www.cancer.org/cancer/kidney-cancer/after-treatment/follow-up.html 

American Kidney Fund. (2021, November 6). Chronic kidney disease (CKD). https://www.kidneyfund.org/all-about-kidneys/chronic-kidney-disease-ckd 

Centers for Disease Control and Prevention. (2022, July 12). Link Between Chronic Kidney Disease, Diabetes, and Heart Disease. https://www.cdc.gov/kidneydisease/publications-resources/link-between-ckd-diabetes-heart-disease.html 

Cleveland Clinic. (2022, July 19). Pericardium: Function and Anatomy. https://my.clevelandclinic.org/health/body/23561-pericardium 

Erythropoietin | You and Your Hormones from the Society for Endocrinology. (n.d.). https://www.yourhormones.info/hormones/erythropoietin/ 

Glass, D. (2016, July 22). How Humans Are Like Rats. A Moment of Science – Indiana Public Media. https://indianapublicmedia.org/amomentofscience/how-humans-are-like-rats.php 

HealthMatters.io. (n.d.). Lipid Peroxides (Genova) | Healthmatters.io. https://healthmatters.io/understand-blood-test-results/lipid-peroxides-genova 

Laminate Medical. (2017, January 11). Effects of Kidney Failure on Body Systems | Laminate Medical. Laminate Medical Technologies. http://www.laminatemedical.com/2017/01/11/effects-kidney-failure-body-systems/ 

Mayo Clinic. (n.d.). Arteriosclerosis / atherosclerosis – Symptoms and causes. https://www.mayoclinic.org/diseases-conditions/arteriosclerosis-atherosclerosis/symptoms-causes/syc-20350569 

Mayo Clinic. (2021, March 15). Kidney cancer – Symptoms and causes. https://www.mayoclinic.org/diseases-conditions/kidney-cancer/symptoms-causes/syc-20352664 

Meléndez-Flores, J. D., & Estrada-Bellmann, I. (2020). Linking chronic kidney disease and Parkinson’s disease: a literature review. Metabolic Brain Disease, 36(1), 1–12. https://doi.org/10.1007/s11011-020-00623-1 

National Kidney Foundation. (n.d.). Kidney Cancer. https://www.kidney.org/atoz/content/kidney-cancer 

Nciri, R., Allagui, M. S., Bourogaa, E., Saoudi, M., Murat, J. C., Croute, F., & Elfeki, A. (2011). Lipid peroxidation, antioxidant activities and stress protein (HSP72/73, GRP94) expression in kidney and liver of rats under lithium treatment. Journal of Physiology and Biochemistry, 68(1), 11–18. https://doi.org/10.1007/s13105-011-0113-3 

Pellegrino, D., La Russa, D., & Marrone, A. (2019). Oxidative Imbalance and Kidney Damage: New Study Perspectives from Animal Models to Hospitalized Patients. Antioxidants, 8(12), 594. https://doi.org/10.3390/antiox8120594 

Schoener, B., & Borger, J. (2022, December 5). NCBI – WWW Error Blocked Diagnostic. https://www.ncbi.nlm.nih.gov/books/NBK536997/ 

Impacts of Lithium Pollution on Humans and Animals Part 1

As mentioned in the previous blogs, the rapid growth in demand for lithium-ion batteries and low rates of recycling due to the low cost of production has resulted in Li pollution when these batteries are discarded into landfills with other municipal waste. This sudden increase in Li in the environment impacts marine life, plants, animals, and humans. In the next few blogs, I will explore more about the impacts Li have on animals and humans. 

With the increasing concentration of Li in the environment, concerns about prolonged exposure to high concentrations of Li are also rising. As more Li leaks into the environment, into water and food sources, Li will enter the food chain as animals and humans consume contaminated plants, animals and water. To understand the impacts consuming Li has on humans and animals, experiments have been conducted on animals such as rats.

Figure 1: (Magazine, 2019

Experiments on young Wistar male rats conducted by Nciri et al. (2011) have found significant changes to the chemical and biological activities in the kidneys and liver of rats even at low concentrations of Li. Experiment rats were fed food and water with the same concentrations of Li over different periods and changes were observed over a period of up to 28 days (Nciri et al., 2011). 

Significant changes observed: 

1. Decrease regulating function of liver and kidney

This treatment led to serum concentrations ranging from 0.5 mM (day 7) to 1.34 mM (day 28) and renal insufficiency highlighted by an increase of blood creatinine and urea levels and a decrease of urea excretion. – Nciri et al., 2011

Creatinine is waste matter from muscles that are excreted from the body through urine (American Kidney Fund, 2022). A healthy liver will ensure a sufficient amount of creatinine is excreted out of the body to ensure a healthy level of blood creatinine (American Kidney Fund, 2022). An increase in blood creatinine indicates that the kidney is no longer functioning healthily. 

Urea on the other hand is a chemical waste product and an important circulating source of nitrogen compounds that remove waste products from the bloodstream (Weiner et al., 2015). Urea is produced in the liver before being transported to the kidney where it is filtered to remove waste products from the body (Mayo Clinic, 2021). It is essential to the regulatory function of the kidney (Weiner et al., 2015). A decrease in urea excretion will result in a reduction of chemical waste removed from the body. 

2. Damage to tissues

Lithium treatment was found to trigger an oxidative stress both in kidney and liver, leading to an increase of lipid peroxidation level (TBARS) and of superoxide dismutase and catalase activities.- Nciri et al., 2011

Oxidative stress occurs when there is a disproportion between antioxidant activity and free radical activity (Dix, 2018). Prolonged/severe oxidative stress can damage renal tissue (HealthMatters.io, n.d.), the connective tissue that surrounds and supports the kidney (Gyurászová et al., 2020; National Cancer Institute, n.d.). Renal tissue will lead to kidney failure and related diseases which will be explored more in the next blog. 

 

Reference List

American Kidney Fund. (2022, January 5). Serum creatinine test. https://www.kidneyfund.org/all-about-kidneys/tests/serum-creatinine-test 

Dix, R. M. N. (2018, September 29). Everything You Should Know About Oxidative Stress. Healthline. https://www.healthline.com/health/oxidative-stress 

Gyurászová, M., Gurecká, R., Bábíčková, J., & Tóthová, U. (2020). Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers. Oxidative Medicine and Cellular Longevity, 2020, 1–11. https://doi.org/10.1155/2020/5478708 

HealthMatters.io. (n.d.). Lipid Peroxides (Genova) | Healthmatters.io. https://healthmatters.io/understand-blood-test-results/lipid-peroxides-genova 

Magazine, S. (2019, February 27). The History of the Lab Rat Is Full of Scientific Triumphs and Ethical Quandaries. Smithsonian Magazine. https://www.smithsonianmag.com/science-nature/history-lab-rat-scientific-triumphs-ethical-quandaries-180971533/ 

Mayo Clinic. (2021, August 19). Blood urea nitrogen (BUN) test – Mayo Clinic. https://www.mayoclinic.org/tests-procedures/blood-urea-nitrogen/about/pac-20384821 

National Cancer Institute. (n.d.). Kidneys | SEER Training. https://training.seer.cancer.gov/anatomy/urinary/components/kidney.html 

Nciri, R., Allagui, M. S., Bourogaa, E., Saoudi, M., Murat, J. C., Croute, F., & Elfeki, A. (2011). Lipid peroxidation, antioxidant activities and stress protein (HSP72/73, GRP94) expression in kidney and liver of rats under lithium treatment. Journal of Physiology and Biochemistry, 68(1), 11–18. https://doi.org/10.1007/s13105-011-0113-3 

Weiner, I. D., Mitch, W. E., & Sands, J. M. (2015). Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion. Clinical Journal of the American Society of Nephrology, 10(8), 1444–1458. https://doi.org/10.2215/cjn.10311013