The liver is often touted as a multi-tasking, hardworking organ that performs various processes that support digestion, detoxification, metabolism, immunity, nutrient storage, as well as other physiological functions1. Because this important organ is involved in so many crucial biological processes, protecting the liver is a priority.
In this article, we reveal two little known facts about liver issues. Inflammation, fatty liver, hepatitis, fibrosis, and cirrhosis are conditions that affect the liver. Although these conditions may be attributed to different causes, did you know that these liver conditions share two common underlying factors? In fact, scientists assert that liver health hangs in the balance of these two factors:
- Oxidative Stress; and
- Mitochondrial Dysfunction.
What triggers these factors, how do they impact the liver, and (most importantly) what can we do? Read on to find out!
Fact #1: Chronic Oxidative Stress Damages the Liver
What is oxidative stress?
Oxidative stress is a state of imbalance within our body’s inbuilt antioxidant system. It occurs when the equilibrium between reactive oxygen species (ROS) generation and the body’s free-radical-scavenging capacity is disrupted. Generation of ROS is a normal physiological mechanism. The problem arises when excessive levels of ROS overwhelm the body’s antioxidant system, damaging and modifying tissues and cells – which can eventually lead to cell death.
How does oxidative stress affect the liver?
Regardless of the cause, chronic liver disorders almost always involve oxidative stress2,3. Because of its many metabolic functions, the liver is highly susceptible to oxidative stress. The liver has an inbuilt antioxidant defence system that maintains a fine balance between ROS and antioxidant molecules. When excessive ROS levels cannot be counterbalanced, oxidative stress within the liver exacerbates progression of liver damage. This is because oxidative stress damages cell components - lipids, proteins, and DNA - in the liver which can trigger liver cell death and amplify inflammation. Excessive ROS can also trigger cell signals which initiates liver fibrosis, changing the normal architecture of the liver, ultimately altering liver function.
What eliminates or minimises oxidative stress?
Long answer short: antioxidants! The inbuilt antioxidant system within our cells uses antioxidant molecules to inactive ROS or prevent their negative effects. Some of these antioxidants are synthesised endogenously by the body; diet is the main exogenous antioxidant source. When antioxidant capacity decreases, levels of inactivated ROS increases. There are two types of antioxidants:
- Non-enzymatic antioxidants: ascorbic acid (vitamin C), α-tocopherol (vitamin E), glutathione (GSH), carotenoids, flavonoids, polyphenols, and other antioxidants.
- Enzymatic antioxidants: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).
Fact #2: Mitochondrial Dysfunction is a Cause/Consequence of Chronic Liver Disorders
What are mitochondria?
|Image Source: NHGRI|
Mitochondria are the powerhouse of cells.
As an energy-intensive organ, the liver is extremely rich in mitochondria. Most, if not all, liver functions require energy – which is generated by mitochondria. These organelles are specialised structures within cells that provide energy for metabolic activities. Although occurrence and progression of liver diseases can be attributed to different factors, scientists have discovered a common link in most chronic liver diseases – mitochondrial dysfunction4.
How does mitochondrial dysfunction affect the liver?
Mitochondrial dysfunction plays a complex role in liver disorders – acting as a cause and/or consequence of liver disease progression5. Dysfunctional liver mitochondria results in energy shortage required for liver functions and processes, excessive production and leakage of damaging ROS, and excessive lipid accumulation which may escalate to liver inflammation and liver cell death4,6.
What causes mitochondrial dysfunction?
High-fat, high-sucrose diets have been shown to decrease liver mitochondrial content and mitochondria DNA levels, increase oxidative stress, and hinder energy production within cells – all of which can contribute to mitochondria dysfunction.
Reducing oxidative stress and maintaining healthy mitochondrial functions may help prevent, reverse, or halt progression of various liver disorders.
- Aerobic exercise may stimulate mitochondrial biogenesis;
- Endurance exercise and reduced caloric intake may increase mitochondria proliferation and function.
- Increasing polyunsaturated fatty acids and antioxidants can help eliminate or minimise oxidative stress and prevent mitochondrial dysfunction.
- Research shows Ganoderma Lucidum (lingzhi) has potent hepatoprotective effects on liver injury8-10;
- Ganoderma Lucidum triterpenoids protect against oxidative damage by enhancing levels of glutathione and enzymatic antioxidants i.e. SOD, GpX and CAT11.
- Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol. 2017;27(21):R1147-R1151. doi:10.1016/j.cub.2017.09.019
- Cichoż-Lach H. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol. 2014;20(25):8082. doi:10.3748/wjg.v20.i25.8082
- Li S, Tan H-Y, Wang N, et al. The Role of Oxidative Stress and Antioxidants in Liver Diseases. Int J Mol Sci. 2015;16(11):26087-26124. doi:10.3390/ijms161125942
- Arauz J, Ramos-Tovar E, Muriel P. Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside. Ann Hepatol. 2016;15(2):160-173. doi:10.5604/16652681.1193701
- Auger C, Alhasawi A, Contavadoo M, Appanna VD. Dysfunctional mitochondrial bioenergetics and the pathogenesis of hepatic disorders. Front Cell Dev Biol. 2015;3. doi:10.3389/fcell.2015.00040
- García‐Ruiz C, Fernández‐Checa JC. Mitochondrial Oxidative Stress and Antioxidants Balance in Fatty Liver Disease. Hepatol Commun. 2018;2(12):1425-1439. doi:10.1002/hep4.1271
- Degli Esposti D, Hamelin J, Bosselut N, et al. Mitochondrial Roles and Cytoprotection in Chronic Liver Injury. Biochem Res Int. 2012;2012:1-16. doi:10.1155/2012/387626
- Lin Z, Deng A. Antioxidative and Free Radical Scavenging Activity of Ganoderma (Lingzhi). In: Advances in Experimental Medicine and Biology. Springer Nature Singapore Pte Ltd; 2019:271-297. doi:10.1007/978-981-32-9421-9_12
- Qiu Z, Zhong D, Yang B. Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Liver Injury. In: Lin Z, Yang B, eds. Ganoderma and Health. Singapore: Springer; 2019:217-242. doi:10.1007/978-981-32-9421-9_9
- Wachtel-Galor S, Yuen J, Buswell JA, Benzie IFF. Ganoderma lucidum (Lingzhi or Reishi): A Medicinal Mushroom. In: Benzie IFF, Wachtel-Galor S, eds. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd ed. Boca Raton (FL): CRC Press/Taylor & Francis; 2011.
- Yang Y, Zhang H, Zuo J, et al. Advances in research on the active constituents and physiological effects of Ganoderma lucidum. Biomed Dermatology. 2019;3(1):6. doi:10.1186/s41702-019-0044-0
- Lushchak VI. Free radicals, reactive oxygen species, oxidative stresses and their classifications. Ukr Biochem J. 2015;87(6):11-18. doi:10.15407/ubj87.06.011
- Xuan W, Song D, Yan Y, Yang M, Sun Y. A Potential Role for Mitochondrial DNA in the Activation of Oxidative Stress and Inflammation in Liver Disease. Guaragnella N, ed. Oxid Med Cell Longev. 2020;2020:1-10. doi:10.1155/2020/5835910
Disclaimer: This article is intended for educational enlightenment and is not designed to diagnose, treat, or cure. Every individual is unique – if you have any health concerns, do discuss them with a medical or health professional.
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