The liver is the largest organ in the abdominal cavity and one of the most important in the body[1, 2, 3]. It has numerous vital functions, including detoxification, metabolic support, particle filtration, synthesis of plasma proteins, secretion and excretion of bile, metabolism of vitamins A, B, D and K and participation in hematopoiesis.
It is a highly vascularized organ and therefore highly exposed to various compounds absorbed through the gastrointestinal tract. Due to its role in the processing, biotransformation and detoxification of xenobiotics, i.e. chemical agents foreign to the body which must be eliminated in order to prevent damage to health, the liver is regularly exposed to potentially harmful compounds[3].
The most common response of liver cells to non-lethal insults is hepatocellular degeneration, where degenerated cells can accumulate substances such as fat, glycogen and copper. Often, hepatocellular degeneration is reversible and transient, however, more serious lesions can progress to cell death through necrosis or apoptosis, which is programmed cell death [2].
In addition, cholestatic liver disease can occur when liver damage interferes with the ability of hepatocytes to excrete bile, which can be caused by metabolic derangements in hepatocytes, hepatocellular swelling, obstructions in the bile ducts or gallbladder obstruction [2]. Furthermore, hepatic steatosis or lipidosis, also known as "fatty liver", is a common marker of moderate to severe hepatocellular insult. In this case, the hepatocytes become distended with fat. Although it is benign and reversible without treatment, it can progress and result in chronic progressive liver damage, fibrosis and even neoplasia [2].
The good news is that the liver has a great capacity for repair and regeneration after acute or chronic insults. Who hasn't seen that well-known picture from Greek mythology where Prometheus has his liver eaten by a raven? The painting represents its capacity for regeneration. The extent of regeneration depends on the balance between various factors, such as the regulation of the cell cycle, metabolism and angiogenesis, among others[2].
To aid this process, there are many nutraceuticals with antioxidant, anti-inflammatory, anti-fibrotic, anti-proliferative and anti-neoplastic potential that can be used to improve the functioning and health of this organ! Let's take a look at some of them:
S-Adenosylmethionine (SAMe):Â Used in veterinary medicine as an adjunct therapy in the management of liver diseases due to inflammation, metabolism or cholestasis, mainly in dogs and cats. It is useful for re-establishing hepatocellular function, attenuating the production of free radicals, reducing inflammation, improving detoxification mechanisms and eliminating toxic agents, as well as improving membrane function and stimulating hepatocellular repair [2].
N-acetylcysteine (NAC):Â Used in imminent or present cases of severe liver intoxication and situations involving oxidative damage to red blood cells. In veterinary medicine, it has been recommended for poisoning caused by paracetamol, diazepam, non-steroidal anti-inflammatory drugs, toxic mushrooms and hepatic lipidosis syndrome associated with hemolytic anemia due to Heinz corpuscles [2].
Silymarin (Milk thistle extract):Â it has antioxidant action, improves hepatocellular regeneration by accelerating DNA synthesis and reduces liver fibrosis as it inhibits the formation of reactive collagen in liver lesions. The stimulation of bile acid synthesis by silymarin results in increased bile flow. It also has hepatoprotective activity and in various xenobiotic-induced hepatotoxicoses, including those caused by hepatotoxic mushrooms, paracetamol, iron, cisplatin and methotrexate, among others [2].
Vitamin E: This is an essential fat-soluble vitamin with great antioxidant capacity. It is absorbed by the proximal intestine, and the degree of absorption depends on the amount of lipids ingested and the amount of bile secreted, as well as the presence of digestive enzymes. The most important role of vitamin E is to reduce the damage caused by peroxidation of the hepatocellular membrane [2].
Curcumin: It is widely used to treat a variety of health problems due to its antioxidant, antimicrobial, anti-inflammatory, antiviral, anticancer and antidiabetic properties. Curcumin reduces the level of hepatic steatosis and prevents the reduction of cytochrome P450 expression, which is responsible for facilitating the excretion of undesirable substances, as well as the activation or deactivation of many drugs, toxins, etc. [3].
EPA/DHA: These are polyunsaturated essential fatty acids whose supplementation reduces cholesterol and triglyceride levels.
Berberine: Excellent regulator of lipid metabolism, with an antihyperlipidemic effect, reducing cholesterol and triglycerides, as well as regulating bile acids. It also has anti-inflammatory, antioxidant, anti-fibrotic and anti-cancer effects, which contribute to protecting the liver [5].
Ellagic acid: Present in various fruits, such as pomegranate, it has antioxidant activity and acts on lipid peroxidation, protecting cells from oxidative damage.It has a protective effect against various substances that impair liver function.It is also beneficial for chronic diseases associated with oxidative damage, including cancer[1].
Spirulina (Arthrospira platensis): A microscopic, filamentous algae with high nutritional value, it contributes to reducing lipemia and glycemia, as well as acting as an antiviral, liver protector, anticancer, anti-inflammatory and antioxidant.It also acts as a heavy metal chelator [2].
Taurine: Acts as an antioxidant and cell membrane structurer and its supplementation helps to reduce blood cholesterol levels, preventing the exacerbation of liver damage in cholestatic disease [4].
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References:
1)  ASLAN, A. et al. Ellagic acid impedes carbontetrachloride-induced liver damage in rats through suppression of NF-kB, Bcl-2 and regulating Nrf-2 and caspase pathway. Biomedicine & Pharmacotherapy, v. 105 (2018), pp. 662–669.
2)Â Â Â GUPTA, R. et al. Nutraceuticals in Veterinary Medicine. Ed. Springer Nature Switzerland AG, 2019.
3)Â Â GUPTA, R. Nutraceuticals: Efficacy, safety and toxicity. Ed. Elsevier, 2016.
4)Â Â RODELLA, P. et al. The Effect of Taurine on Hepatic Disorders. Curr Updates Hepatol Gastroenterol. (2017) 1: 1.1.
5)Â Â ZHOU, M. et al. The pharmacological activity of berberine, a review for liver protection. European Journal of Pharmacology. 2021 (Article in Press)
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