HepaSure® is a Veterinarian Recommended Liver Supplement for Dogs.
What Exactly Is the Liver?
The liver is one of the largest organs, and it is also one of the most important glands in the body. Glands are organs that make (synthesize) substances that are discharged into the bloodstream or other areas.
The liver plays a primary role in all of the metabolic processes throughout the body. It secretes bile, a bitter, brownish-yellow or greenish-yellow fluid that aids in the digestion of fats. Bile consists of acids and salts that surround and break down fat globules in food so that they can be absorbed into the small intestine.
The body stores bile in the gallbladder, a sac located just below the liver until it is secreted into the intestines to aid in the digestion and absorption of fats. These “bile acids” are then reabsorbed back into the blood via the portal system. These bile acids then re-enter the liver where they are extracted and stored again until they are needed again.
Dogs with liver shunts have increased concentrations of bile acid in their blood because these chemicals bypass the liver and are neither removed or stored.
What is Metabolism?
Metabolism is the combination of physical and chemical actions that take place inside of the body to serve and maintain life. The metabolic process either breaks down (metabolizes) substances to convert dietary nutrients into energy or synthesizes the elements necessary for life.
What Does the Liver Do?
The liver serves three main functions for your dog:
The liver works as a manufacturing facility, producing chemicals necessary for the body to operate - including certain proteins required for a variety of bodily functions, such as blood clotting, and the manufacture of albumin, a protein necessary for maintaining the oncotic pressure of the blood. It is the oncotic pressure that keeps the blood inside the blood vessels rather than seeping out into the tissues and body cavities.
The liver serves as a storage facility for vitamins (A, D, E, and K), minerals (iron), glycogen, and triglycerides. Vitamin A is vital for vision and eye health. Vitamin D aids in calcium absorption. Vitamin K is crucial for blood clotting. Iron is necessary for the formation of red blood cells. Glycogen is converted into glucose and used as energy. Triglycerides are a type of fat that provides energy for cell function.
The liver acts as a processing plant, breaking down and detoxifying every substance that your dog consumes. The liver breaks down proteins, fats, and carbohydrates and converts them into glucose (sugar), that the body uses for energy. The liver also metabolizes any medications and detoxifies dangerous substances, such as ammonia, damaged red blood cells, and cellular debris. It takes these toxins and either converts them into harmless substances or isolates them and transports them to the kidneys and intestines for removal.
The cells of the liver called hepatocytes perform all of these duties. Hepatocytes have regenerative properties and provide the liver its distinctive ability to regrow its own dead or damaged tissue.
Why is the Liver so Important?
The small intestine absorbs all of the nutrients, medications, and toxins that the stomach digests. The blood from the small intestines then travels to the liver, by way of the portal vein. in a loop known as hepatic portal circulation. Therefore, everything that your dog ingests, whether toxic or nutritionally beneficial, must flow through the liver before it is sent to his heart where it is then pumped throughout the rest of his body.
Every substance must pass the scrutiny of the liver, where the liver transforms it into a biochemical form. This transformation is what permits the nutrients to be used, carried to another part of the body, or stored as fat. Ultimately, the liver determines what is allowed to stay in the body, what gets dispersed and redirected throughout the body, and what gets eliminated.
Why Do Dogs Need a Liver Supplement?
A dog's liver suffers from exposure to toxins, old age, genetics, injury, infections, parasitic infestations, and overall stress. All of these things can stress a dog’s liver, impinging the liver’s ability to remove impurities from the blood. When the liver becomes stressed, a condition called hepatitis develops. Hepatitis is a disease that is distinguished by inflammation of the liver.
Exposure to Toxins
The liver is more susceptible to damage than other organs because of its chief role in metabolizing harmful substances. Toxin-induced hepatitis usually occurs with diets high in fat and prolonged exposure to higher than normal levels of toxins.
Hepatotoxins are harmful substances that damage your dog’s liver. Some are known to cause liver damage and that, in turn, frequently leads to liver toxicity. Some examples of common substances commonly known to cause liver toxicity include:
- Medications - when taken in large doses or for long periods of time
- Foods - chocolate, or the sweetener, xylitol
- Pesticides and insecticides
- Household cleaners
- Rat poison
- Lead paint chips
- Toxic Plants around the home and garden
The build-up of these toxins in a dog’s body can overwhelm the digestive system. Leaving these toxins untreated can result in serious illnesses. When the liver fails at removing impurities, your dog’s body will attempt to expel the excess toxins through other means. The body expels toxins through:
- The skin - resulting in itchy, scaly, flaky, or dry skin
- The mucous membranes - produces a runny nose or eye discharge
- Fat storage - resulting in the excess toxins remaining in the body, thus causing further health issues in the future
Harmful substances of any kind can result in death and inflammation of the liver cells, leading to the damaged tissue being replaced by fibrous scarring. This process can lead to fibrosis and is the first stage of liver scarring. Fibrosis can be a self-perpetuating cycle that ultimately results in cirrhosis of the liver. Cirrhosis is the result of scar tissue building up in the liver and impeding its normal function.
Young puppies and senior dogs with poor liver health are most susceptible to adverse reactions from prescription medications (Rx) and chemicals due to declined metabolism and functionality.
Some breeds are more susceptible to developing a copper storage disease, known as canine copper hepatotoxicosis. Nutritionally speaking, copper is a micronutrient that is necessary for the daily cellular functions of enzymes, proteins, and antioxidants. Once copper has passed through the stomach and small intestine, it travels to the liver via the portal vein where the liver metabolizes it. Genetics, however, can impact the way a dog's liver uses, stores, and excretes copper. Abnormal and excessive buildup of copper in a dog’s liver is referred to copper storage hepatopathy and can cause progressive scarring and liver damage (cirrhosis) and can lead to death.
Some terrier breeds, such as Bedlington Terriers, are at greater risk for inheriting a metabolic defect that impairs the liver’s ability to excrete copper. These dogs lack a particular gene (COMMD1) coding for a liver protein that is responsible for expelling copper into bile so that it can be discharged from the body.
Copper storage has been linked to several other breed-related hepatopathies, including liver disorders presenting in:
- West Highland Terriers
- Skye Terriers
- Labrador Retrievers
- German shepherds
In these dogs, inflammatory liver disease such as hepatitis can promote and accelerate copper accumulation in the liver because of chronic cholestasis, a condition in which the flow of bile is slowed or stopped.
This genetic disposition doesn’t mean that these particular breeds are destined to develop liver problems, nor does it mean that other breeds are not vulnerable. It means that owners of these breeds should be watchful for possible liver complications and take special care to maintain the health of their dog’s liver.
A liver shunt is an abnormal blood vessel connection between the portal vein or one of its branches that carry blood around the liver rather than through it for filtration, thus allowing blood to bypass (shunt) around the dog’s liver.
Shunts can develop as a congenital defect (congenital portosystemic shunt) while a puppy is still in its mother’s womb or later on in life as the result of cirrhosis or other diseases of the liver (acquired portosystemic shunt).
Trauma can cause a dog’s liver to improperly function. An injury to the liver can cause one of the lobes to fracture and bleed into the abdomen. Traumatic damage to the liver can be potentially fatal to dogs and can include such injuries as:
- Blunt trauma injuries. (Usually car accidents)
- Hernia to the diaphragm
Bacterial, Fungal, Parasitic, and Viral Infections
- Leptospirosis - a bacterial infection that is common in wildlife that can be transmitted to dogs and other domestic pets via contaminated water.
- Histoplasmosis - a fungal infection caused by dogs inhaling or ingesting spores found in contaminated soil or bird droppings.
- Toxoplasmosis - a parasitic infection affecting cats during the first stage of its lifecycle. Once it passes through the cat, it looks for a warm-blooded host to survive. Dogs become infected when they ingest contaminated food, eat dead (infected) rodents or birds, and consume cat feces laden with parasites.
- Heartworms - worms can cause liver failure by blocking the flow of blood into the liver.
- Canine Infectious Hepatitis - Inflammation of the liver that is usually caused by a highly contagious viral infection. Transmitted by mouth (ingestion) from one dog to another.
- Lyme Disease - Mild hepatitis of the liver. Usually transmitted by an infected tick.
The pancreas and liver are near one another. Often, inflammation of the pancreas can transfer over into the liver and cause liver inflammation (hepatitis).
How Does the Liver Detoxify the Body?
Some elements that go into a dog’s digestive system are far from pure. Regardless of how carefully you regulate your dog’s diet, environmental toxins are inevitable and sometimes unavoidable. All of these impurities and toxins that enter your pet carry with them the potential to harm cells and destroy tissue.
The liver sorts and handles these environmental toxins because of hepatic portal circulation. Approximately 1-2 liters of blood per minute pass through the liver for detoxification. The liver can “clean” large volumes of blood quickly.
Once inside of the liver, the blood flows over rows of cells, called Kupffer cells. These Kupffer cells act as a strainer and serve to filter impurities out of the bloodstream as blood flows through them. Kupffer cells have a vital role in cleansing the blood of used, worn-out red blood cells, bacteria, cellular debris, fungi, and parasites by isolating and destroying them before passing what’s left of them along to the hepatocytes. The hepatocytes metabolize the remains.
Many of the toxins that enter your dog’s body are fat-soluble, meaning that they are not able to be dissolved in water and readily excreted through the kidneys. Therefore, these harmful substances require fatty or oily solutions to be dissolved and broken down for elimination. The body manages this problem by converting fat-soluble toxins into inactive water-soluble metabolites.
Enzymes in the liver used a two-step detoxification pathway to neutralize toxins:
Phase I (Transformation): Liver enzymes transform fat-soluble compounds into water-soluble compounds using a variety of different chemical reactions, such as oxidation and reduction (chemical reactions in which an atom or ion loses electrons to another atom or ion). Phase I prepares harmful substances for elimination from the body. However, the process produces free radicals. In excess, free radicals can cause liver damage, but antioxidants such as milk thistle and Vitamins A, C, D, and E can reduce the damage they can cause.
Phase II (Conjugation): Enzymes accomplish the “solubilization” of toxins which connect (conjugate) water-soluble molecules to the fat-soluble toxin. Liver cells add other substances such as cysteine, glycine or a sulfur molecule to the transformed, toxic chemical or drug, rendering it even less harmful. This process makes the toxin water-soluble, so it passes from the body via bile or urine. During Phase 2, the liver cells require sulphur-containing amino acids such as taurine and cysteine as well as other nutrients such as glycine, glutamine, cysteine, and selenium.
Is My Dog Having Liver Problems?
The most common symptoms of liver issues in dogs are:
- Loss of appetite
- Unexplained, sudden weight loss
- Pale gums
- Swollen abdomen
- Dark urine
- Jaundice (a yellow discoloration of the skin, whites of eyes, and gums)
If your dog is presenting with ANY of these symptoms, or if you suspect that your pet has any signs of liver damage, it is imperative that you see your vet for a diagnosis of any liver problems.
If caught early enough, canine liver disease can be managed and treated by your veterinarian. Successful treatment depends on the severity and underlying cause of the disease. Therapeutic goals include:
- Eliminate toxins and reduce the amount of damage they can cause.
- Promoting regeneration and recovery of liver tissue.
- Manage any other complications of liver dysfunction.
- If possible, treat the underlying cause of liver distress.
What are Natural Treatments for a Dog Liver Problems?
There are various treatments and therapies available for canine liver disease. The treatments depend on the type of disorder and the amount of liver damage. While your dog may require veterinary care in certain circumstances (surgery, hospitalization, vaccines, medications), you can help support your dog’s liver health by keeping him active and ensuring he gets the proper types of nutrients and supplements.
Some of the natural treatments to help improve a dog’s liver include:
Exercise helps circulate the blood through the body. As blood circulates, it passes through the liver for detoxification. Also, many toxins that your dog has absorbed are stored in fatty tissue. Exercise helps reduce the amount of fat, and therefore, toxins, stored in the body
Dietary therapy assists with the treatment of a dog with liver disease. A proper diet ensures that your dog receives the necessary nutrients that it needs while decreasing unnecessary stress on the liver. Dogs with liver disease benefit from diets containing:
- Carbohydrates - These carbohydrates need to be both high quality and easily digestible. White rice, vegetables, and potatoes are good choices. Inferior carbohydrates digest poorly and ferment in the intestines, increasing bacteria in the colon. These bacteria break down proteins from the dog’s food, causing ammonia buildup and contributing to toxicity in the liver. Vegetables are an excellent source of complex carbohydrates because they contain fiber. Fiber helps bind intestinal toxins, and it stimulates bowel movements to excrete toxins from the body
- Protein - It must be a moderate serving size of a high-quality protein. Sources should be low in copper and Vitamin A, which are known to contribute to the symptoms of liver disease. Organ meat, especially beef liver, should be avoided, in addition to duck, pork, salmon, and lamb. We recommend non-meat protein sources, including eggs and dairy products.
- Low Sodium - Because high salt diets build-up fluid in the abdomen, low sodium diets are reommended.
Natural supplements can protect the liver from harmful substances. They can work as anti-inflammatories and stimulate digestive enzymes
What Are the Best Natural Liver Supplements for Dogs?
Milk thistle is a flowering herb from the Aster family. It is one of the most popular liver supplements for both humans and canines - so much so that it is usually the first course of treatment for poisoning victims in Europe. It is not a drug or prescription and offers your dog natural support.
Its Latin name is Silybum marianum, and its use dates back to the Roman Empire when people used it to detoxify their livers. Recently, it has gained acclaim and recognition as an effective supplement for dogs. Animal studies also suggest that milk thistle extracts can help guard the liver against many other toxins, including acetaminophen and toluene (a natural solvent).1
Milk thistle detoxifies the liver, and it also serves to block the uptake of toxins, including acetaminophen and toluene (a natural solvent)2. Traditionally, it has been used as an emergency antidote for death cap mushroom poisoning and can significantly reduce the risk of liver damage and death if given within 24 hours of consuming the mushrooms. If taken within 10 minutes of ingesting the mushrooms, milk thistle can completely counteract the poison.
Milk thistle has been used medicinally throughout history over the past 2,000 years to treat a variety of liver and gallbladder-related problems. It wasn’t until 1968, however, that scientists in Germany discovered a three-part flavonoid compound, collectively known as silymarin, found in the seeds of the plant.3 Since then, hundreds of studies have focused on the benefits of silymarin. As a result of this research, scientists have found that three components, silybin, silydianin, and silychristin, can help repair damaged liver cells.
Studies in humans indicate that milk thistle extracts may have anti-cancer effects. Specifically, studies have shown that it may help fight cancer by:
- Slowing the growth of certain cancer cells
- Enhancing the activity of some chemotherapy drugs, thus making them more potent
- Preventing the affected cancer cells from dividing by shortening their lifespan and by reducing blood supply to the cancer cells
Research is still ongoing regarding silymarin’s effect on cancer treatment. Specifically, whether or not it should be used in the treatment of liver cancer because it promotes liver regeneration thus possibly stimulating rather than inhibiting the growth of certain types of liver cancer.4
Human studies involving milk thistle indicate it promotes healthy kidney function in patients who have experienced kidney damage as a result of diabetes.5 Research also suggests that milk thistle may protect the kidneys from the toxic effects of certain drugs and radiation injury.6
Milk thistle preparations usually are extracts that come from crushed seeds. This extract is standardized to contain a specific concentration of silymarin, typically between 70-80%.
Milk thistle works in a variety of ways to promote liver health:
- It stimulates protein synthesis in a dog’s liver. This protein synthesis results in an increase in the production of new liver cells to replace those damaged by toxins, disease, or injury. New liver cells enable the liver to repair itself and regenerate itself.7
- It is an antioxidant. Antioxidants neutralize free radicals that build up in cells and can cause damage. Free radicals are particles that move around the cell and cause damage to everything in their pathway. Antioxidants stop free radicals.
Silymarin's antioxidant properties are also thought to be at least ten times more potent than vitamin E.8
- It boosts levels of the antioxidant enzyme superoxide dismutase in cell cultures. This enzyme exists in all living cells. It speeds up chemical reactions in the body and helps to rebuild tissue by breaking down harmful oxygen molecules in cells.9
- It increases glutathione production in the liver by more than 35% in healthy subjects and an excess of 50% in rats.10 Glutathione is the body’s most powerful antioxidant. It is vital to the body because it is responsible for detoxifying a broad range of hormones, pharmaceuticals, and chemicals. The more glutathione a dog’s liver produces, the better his liver will be able to handle harmful substances and detoxify his body.
What is Glutathione?
Glutathione is a very powerful antioxidant that helps support detoxification. It boosts the immune system and helps support the body repair damage to tissues as a result of injury, toxins, illness, and stress. Every cell in a mammal contains Glutathione. It is a naturally occurring substance that can be produced inside of the body as well as found in food.
Glutathione is made up of three amino acids: cysteine, glutamate, and glycine. It is sometimes confused with glutamine and glutamate because of similar names. However, they differ in function and composition:
- Glutamine is the most plentiful amino acid found in the body. It is a precursor to glutathione and is made inside of the brain from glutamate and is vital to muscle and injury repair.
- Glutathione (of which there are two types, GSH and GSSG), is found in every cell in the body. It is the “master antioxidant” and the most powerful antioxidant. It protects cells from damage, which is particularly important for liver health. When glutathione is broken down, it becomes free glutamate.
- Glutamate (glutamic acid or L-glutamate) is an amino acid neurotransmitter in your brain. Neurotransmitters are like chemical messages that nerve cells send to one another. These “messages” are released into and taken up from synapses, the space between the neurons.
Synaptic activity needs glutamate to occur. However, too much of it can be a bad thing because it is an excitotoxin - a chemical that overstimulates neuron receptors. Glutamate does this by causing these receptors to fire impulses so rapidly that they become exhausted and eventually die.
What Does Glutathione Do?
Glutathione differs from other antioxidants in that it is intracellular, meaning that it exists within the cell, giving it the ability to work from within the cell to keep it functioning properly. It also optimizes the effectiveness of all the other antioxidants, including vitamins C and E, allowing them to do a better job of keeping your dog healthy. It removes toxins from your cells and protects you from the damaging effects of radiation, chemicals, and environmental pollutants.
Glutathione performs many important roles in your dog’s body:
Glutathione detoxifies pollutants including heavy metals, carcinogens, pesticides, and radiation by binding to them and creating a soluble (dissolvable) compound with the toxin. The body can then pass the toxin as waste in the form of urine or bile.
Antioxidant and Immune Support
The availability of glutathione in the body directly affects the growth of healthy, active immune cells. Glutathione helps protect your dog’s immune system by amplifying immune cell activity and functioning as an antioxidant within them. Glutathione is the master antioxidant; your dog depends on it for the removal of toxins from his body. It is at the core of all immune functions, and other antioxidants rely on it to function properly.
Glutathione supports biochemical reactions in your dog’s cells enabling them to process nutrients and convert them into energy more efficiently. It does this by enabling the mitochondria (the cell’s “powerhouse”) to remain fully charged, thus allowing for increased muscle strength and endurance.
Research has demonstrated that lowering glutathione levels in the mitochondria results in the death of the cell.11
Repairs Cells Damaged by Free Radicals
Free radicals are everywhere - they are in the food your dog eats, in the water she drinks, and in the air she breathes. Her body produces free radicals as a by-product of breaking down food - and they are always attacking healthy cells. Free radicals work by attacking the closest stable molecule it comes into contact with, and "steals" its electron. This process is named oxidation.
When a molecule loses an electron, it then becomes a free radical itself, attacking the next closest stable molecule, on and on. Thus begins a chain reaction that, once begun, can ripple through hundreds of molecules. As this happens, again and again, the cell will eventually either die or mutate. These “cell mutations” are often given a more ominous name: Cancer.
Glutathione performs a vital task in repairing the damaged DNA in cells by replacing the stolen electron. It maximizes the cell’s ability to repair itself and reduces the number of cellular mutations that would otherwise take place as a result of the missing electron.
Are Glutathione Supplements Effective?
Glutathione is available as an oral supplement. However, studies have shown that it does not absorb well into tissues - the body does a poor job getting glutathione past the digestive system and into the bloodstream.12 In fact, glutathione supplements may interfere with your dog’s glutathione production.
How Can I Boost My Dog’s Glutathione Levels Naturally?
While supplementing with glutathione for liver health may be ineffective, thankfully there are ways to bolster your dog’s glutathione levels naturally, either by increasing nutrients in his food or by incorporating supplements into his diet. Some of the best liver supplements that aid in detoxification and liver health include Vitamin B complex and Vitamin E. Zinc is also helpful because it serves as an antioxidant to protect the liver from free radicals, and it helps bind copper.
How Does HepaSure® Help Dogs Produce Glutathione?
In addition to milk thistle, HepaSure® supplies dogs with the proper balance of vitamins, minerals, and building blocks necessary to dog liver function and health.
- Whey Protein Isolate - good source of the amino acid cysteine. Cysteine helps the body make glutathione, thus protecting the liver from damage.
- Phosphatidylcholine - protects the liver from viral damage and prevents cell death from chemical toxins such as drugs and poisons.
- DMG (N, N-Dimethylglycine HCl) - supports detoxification and enhances liver function, particularly the excretion of converted toxic materials out of the body.
- TMG (trimethylglycine) (from natural betaine) - may have protective effects on the liver and could prevent fatty liver deposits.
- N-acetyl-cysteine (NAC) - an amino acid that is an antioxidant. It breaks down free-radicals. Both medical doctors and Veterinarians use NAC to treat liver toxicity associated with ingesting acetaminophen and poisonous mushrooms.
- L-Taurine - reduces liver and blood cholesterol levels by improving gallbladder function, allowing it to eliminate cholesterol through bile.13
- Barley Grass whole powder - supports the metabolic process and helps to strengthen and detoxify trace elements, including copper, from the liver.
- Selenium - mineral that helps the body recycle and produce more glutathione. Selenium is a trace element that acts by several mechanisms, including detoxifying liver enzymes, exerting anti-inflammatory effects, and providing antioxidant defense. The presence of selenium helps induce and maintain the glutathione antioxidant system. (Sakaguchi 2000)
- Zinc - an essential dietary nutrient used in numerous protective drugs and preparations. Zinc boost the antioxidant abilities inside of the liver and helps remove copper from the body.
- Vitamin E - recycles glutathione and relies on it for proper functioning and recycling. Supplementation is related to increased glutathione levels.14
- B-Complex - B vitamins work together and play a vital role in many essential enzyme activities. These enzyme activities have many functions and help metabolize carbohydrates and fats, produce red blood cells, and keep the nervous and digestive systems operating properly.
- Riboflavin (Vitamin B2) - helps combine amino acids (including glutathione) into proteins.
- Thiamine (Vitamin B1) - helps sustain glutathione levels along with related enzymes in their active forms.
- Pyridoxine HCl (Vitamin B6) - essential for the proper function and metabolism of many amino acids.
- Folic Acid (Vitamin B9) - helps produce and maintain red blood cells. It also helps prevent changes to cell DNA which can lead to the growth of cancer cells. Folic acid also reduces harmful levels of homocysteine. High levels of Homocysteine can indicate potential heart and kidney disease, as well as kidney failure.
- Cyanocobalamin (Vitamin B12) - acts as a coenzyme to help make and regulate red blood cells and helps iron function properly in the body.
HepaSure® for Dog Liver Health Information:
HepaSure® is manufactured by Nutra-Paws™ Pet Nutrition. Our labs adhere to current good manufacturing practices (cGMP), and dog owners can have peace of mind knowing that our supplements are tested for quality. HepaSure® is made in America under strict supervision and is backed by a 100% money-back guarantee.
Vitamin A should be used cautiously in dogs with liver disease. They tolerate normal levels but should avoid higher amounts. Cod liver oil, which is high in vitamin A, should be used sparingly, if at all.
1. Mulrow, C., Lawrence, V., Jacobs, B., Dennehy, C., Sapp, J., Ramirez, G., ... & Chiquette, E. (2000). Milk thistle: effects on liver disease and cirrhosis and clinical adverse effects: summary.
Retrieved from http://umm.edu/health/medical/altmed/herb/milk-thistle
2. Milk Thistle. (2017). University of Maryland Medical Center.
Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK11896/
3. Wagner, H., Hörhammer, L., & Münster, R. (1968). On the chemistry of silymarin (silybin), the active principle of the fruits from Silybum marianum (L.) Gaertn.(Carduus marianus L.). Arzneimittel-Forschung, 18(6), 688.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/5755805?dopt=Abstract
4. Gazak, R., Walterova, D., & Kren, V. (2007). Silybin and silymarin-new and emerging applications in medicine. Current medicinal chemistry, 14(3), 315-338.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17305535
5. Williams, M. E. (2006). New potential agents in treating diabetic kidney disease. Drugs, 66(18), 2287-2298.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17181372
6. Gaedeke, J., Fels, L. M., Bokemeyer, C., Mengs, U., Stolte, H., & Lentzen, H. (1996). Cisplatin nephrotoxicity and protection by silibinin. Nephrology Dialysis Transplantation, 11(1), 55-62.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/8649653
7. Lovelace, E. S., Wagoner, J., MacDonald, J., Bammler, T., Bruckner, J., Brownell, J., ... & Webb-Robertson, B. J. M. (2015). Silymarin suppresses cellular inflammation by inducing reparative stress signaling. Journal of natural products, 78(8), 1990-2000.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26186142
8. Cody, V., Middleton, E., & Harborne, J. B. (1986). Plant flavonoids in biology and medicine: biochemical, pharmacological, and structure-activity relationships: proceedings of a symposium held in Buffalo, New York, July 22-26, 1985. Progress in clinical and biological research (USA).
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1763650
9. Müzes, G., Deak, G., Lang, I., Nekam, K., Gergely, P., & Feher, J. (1990). Effect of the bioflavonoid silymarin on the in vitro activity and expression of superoxide dismutase (SOD) enzyme. Acta Physiologica Hungarica, 78(1), 3-9.
Retrieved from http://link.springer.com/article/10.1007%2FBF01953184
10. Valenzuela, A., Aspillaga, M., Vial, S., & Guerra, R. (1989). Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta medica, 55(05), 420-422.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/2813578
11. Marí, M., Morales, A., Colell, A., García-Ruiz, C., & Fernández-Checa, J. C. (2009). Mitochondrial glutathione, a key survival antioxidant. Antioxidants & redox signaling, 11(11), 2685-2700.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821140/
12. Allen, J., & Bradley, R. D. (2011). Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. The Journal Of Alternative And Complementary Medicine, 17(9), 827-833.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162377/
13. Nakaya, Y., Minami, A., Harada, N., Sakamoto, S., Niwa, Y., & Ohnaka, M. (2000). Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes. The American journal of clinical nutrition, 71(1), 54-58.
Retrieved from http://ajcn.nutrition.org/content/71/1/54.full
14. Jain, S. K., McVie, R., & Smith, T. (2000). Vitamin E supplementation restores glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children. Diabetes Care, 23(9), 1389-1394.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10977039
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