Glutathione (GSH)- The Master Antioxidant

  • Glutathione is an antioxidant often referred to as the body's "master antioxidant" due to its central role in protecting the body's cells from free radical damage. Glutathione is composed of the amino acids cysteine (formed from methionine), glutamine and glycine and is concentrated in the liver, although it carries out its work throughout the body. This important enzyme is involved in protecting cells from environmental toxins, drugs and alcohol as well as toxins produced by the body itself as a result of normal metabolism. So important to health is glutathione that its depletion leads to cell death.

  • Due to its SH group, glutathione controls many redox reactions. In liver cells, glutathione protects hepatocytes from the damaging effects of free radicals, toxins, heavy metals and hepatotoxic drugs.

  • The effect of glutathione depletion in liver is associated with abnormal and elevated liver enzyme like SGOT and SGPT.

  • The ability of Racemethionine to reduce the liver-toxic effects of hepatotoxins such as acetaminophen and methotrexate has led to the suggestion that it should be added to acetaminophen products. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress.

  • The liver produces glutathione and so controls blood levels. A deficiency of hepatic GSH and other antioxidants and/or an increase in oxidative stress, may contribute to the progression of liver disease. Glutathione is important in the management of patients with alcoholic liver disease and viral hepatitis, particularly those with hepatitis C.

  • Glutathione protects cells in several ways. It neutralizes oxygen molecules before they can harm cells. Together with selenium, it forms the enzyme glutathione peroxidase, which neutralizes hydrogen peroxide. It is also a component of another antioxidant enzyme, glutathione-S-transferase which is a broad-spectrum liver-detoxifying enzyme.

  • Glutathione protects the body from free radical damages as it contains Sulphur donating amino acid- Cysteine (formed from methionine) which helps to destroy harmful toxic materials from the body. Cysteine also functions as an effective binder of harmful heavy metals in the body, the depletion of Cysteine an essential part of Glutathione can result in frequent sicknesses and damages to the liver.

  • Glutathione has several health benefits. Optimal amounts of glutathione are necessary for supporting the immune system, and, in particular, glutathione is required for replication of the lymphocyte immune cells.

  • Glutathione also helps the liver to detoxify chemicals, such as acetaminophen, copper, and cadmium.

  • Glutathione protects not only individual cells but also the tissues of the arteries, brain, heart, immune cells, kidneys, lenses of the eyes, liver, lungs, and skin against oxidant damage. It plays a role in preventing cancer, especially liver cancer, and may also have an anti-aging effect.

  • Glutathione conjugation is an important step in detoxification process that produces water-soluble substances which are excreted via the kidneys. The elimination of fat-soluble compounds, especially heavy metals like mercury and lead, is dependent upon adequate levels of glutathione, which in turn is dependent upon adequate levels of methionine and cysteine. When increased levels of toxic compounds are present, more methionine is utilized for cysteine and glutathione synthesis. Methionine and cysteine have a protective effect on glutathione and prevent depletion during toxic overload. This, in turn, protects the liver from the damaging effects of toxic compounds and promotes their elimination.

  • Oxidative stress was shown to play a major pathogenic role in multiple disease states ranging from the hepatotoxicity of alcohol to the carcinogenicity of many compounds. The major natural defense mechanism against oxidative stress is reduced glutathione, which traps the excess of free radicals.

Glutathione In Alcoholic Liver Disorders

  • The microsomal ethanol-oxidizing system has been the subject of extensive research. A 4-fold induction of cytochrome P4502E1 (CYP2E1) was found in liver biopsy samples from recently alcohol drinking subjects. CYP2E1 activates some xenobiotics (such as acetaminophen) to toxic metabolites. It also generates several species of active oxygen species. Glutathione provides one of the cell's fundamental mechanisms for the scavenging of toxic free radicals.8

  • Alcohol causes liver disease through a variety of pathogenic mechanisms. The major mechanisms include interactions with nutrition and toxic manifestations through generation of oxidative stress and production of the toxic metabolite acetaldehyde.

Toxicity Of Acetaldehyde :-

  • Acetaldehyde, the product of all pathways of ethanol oxidation, is highly toxic. The decreased capacity of mitochondria in alcoholics results elevated acetaldehyde concentrations.

  • Acetaldehyde is a toxic substance that destroys proteins, causes enzyme inactivation, and decreased DNA repair. Moreover, acetaldehyde promotes lipid peroxidation. The binding of acetaldehyde with cysteine, glutathione, or both may contribute to a decrease in liver glutathione. Acetaldehyde adducts also promote collagen production causing fibrosis.

  • Thus, acetaldehyde toxicity plays a fundamental role in alcohol-induced liver injury, and glutathione is a key defense mechanism by inactivating the free radicals generated by acetaldehyde and by binding to acetaldehyde itself.

Glutathione In Hepatitis :-

  • The role of antioxidants, particularly L-glutathione, in chronic liver diseases is shown in a study that reported on the levels of glutathione in liver, blood and lymphocytes of patients with chronic hepatitis C. Glutathione levels in these three sites was significantly reduced in patients with hepatitis C and correlated with the severity of their liver disease as well as with the ability of the hepatitis C virus to replicate.9

  • Repletion of glutathione levels improves the response to interferon treatment in hepatitis cases. By increasing glutathione levels with high intravenous doses in patients with fatty livers (steatosis) (caused by alcoholic hepatitis or viral hepatitis (B or C)), there was a marked improvement in patients' liver tests that lasted for several months after Glutathione treatment.9