the liver is often the organ that is damaged by such chemicals and their metabolites. Recall from Chapter 8 that the livers of genetically susceptible individuals can be damaged by therapeutic doses of some drugs, such as those shown in Figure 8.5. Other xenobiotics ingested accidentally can damage the liver.
Toxic effects to the liver are studied under the topic of hepatotoxicity, and substances that are toxic to the liver are called hepatotoxins. Much is known about hepatotoxicity from the many cases of liver toxicity that are a manifestation of chronic alcoholism.6 Liver injury from excessive alcohol ingestion initially hampers the ability of the organ to remove lipids, resulting in their accumulation in the liver (fatty liver). The liver eventually loses its ability to perform its metabolic functions and accumulates scar tissue, a condition known as cirrhosis. Inability to synthesize clotting factors can cause fatal hemorrhage in the liver.
A wide range of substances can cause hepatotoxicity. Even an essential vitamin, vitamin A, is hepatotoxic in overdoses, a fact that should be kept in mind by health food fans who drink large amounts of carrot juice. Other hepatotoxins include toxins in hormones, tea (germander), and drinking water infested with the photosynthetic cyanobacteria Microcystis aeruginosa. Each year people are killed by eating toxic mushrooms, especially the appropriately named "death cap" mushroom, Amanita phalloides. This fungus produces a mycotoxin consisting of seven amino acid residues, a heptapeptide called phalloidin.
A great deal of information about hepatotoxicity has resulted from observed effects of pharmaceuticals, a number of which have been discontinued because of their damaging effects to the liver. An example of such a hepatotoxic compound tested as a pharmaceutical is fialuridine, which was tested during the mid-1990s as a treatment for viral chronic hepatitis B, a liver disease.7 Seven of 13 patients in the test developed debilitating hepatotoxicity with severe jaundice, along with lactic acidosis due to accumulation of lactic acid, a metabolic intermediate. The seven patients were given liver transplants, but five of them died.
Steatosis, commonly known as fatty liver, is a condition in which lipids accumulate in the liver in excess of about 5%. It may result from toxicants that cause an increase in lipid synthesis, a decrease in lipid metabolism, or a decrease in the secretion of lipids as lipoproteins. An example of a substance that causes steatosis is valproic acid, once used as an anticonvulsant:
Was this article helpful?
Our internal organs, the colon, liver and intestines, help our bodies eliminate toxic and harmful matter from our bloodstreams and tissues. Often, our systems become overloaded with waste. The very air we breathe, and all of its pollutants, build up in our bodies. Today’s over processed foods and environmental pollutants can easily overwhelm our delicate systems and cause toxic matter to build up in our bodies.