Hepatotoxicity
Hepatotoxicity or liver toxicity ( Greek ἧπαρ hépar ' liver ' and τοξικότητα , from toxikón (phármakon) , arrow (poison) 'from toxa ' bow and arrow ',' toxicity ') denotes the property of chemical substances that are toxic to hepatocytes (liver epithelial cells) be. These substances are known as hepatotoxic substances ( substances that are toxic to the liver, hepatotoxins, liver toxins or liver poisons ).
Hepatotoxic substances can cause damage to the liver epithelial cells up to necrosis or liver dystrophy .
Obligatory and optional liver toxins
There are obligatory liver toxins of optional distinction. Obligatory liver toxins damage the liver of every individual in the same way, depending on the dose . The damage can be repeated in animal experiments. Facultative liver toxins only lead to liver damage in a few individuals, the type of damage is not always the same and the damage cannot be reliably caused in animal experiments. The causes of liver damage by a facultative toxin can be sensitization to a certain antigen or genetic enzyme defects that either lead to an increased occurrence of toxic metabolites (metabolic intermediates) or a reduced breakdown of primarily toxic substances.
The obligatory liver poisons include, for example, phosphorus , carbon tetrachloride , chloroform , aflatoxins , arsenic and the poisons of the death cap mushroom . With long enough exposure in a sufficiently high dose, ethanol , certain cytostatics , phenothiazines and ovulation inhibitors also have a hepatotoxic effect .
Mechanisms of liver damage
With regard to the type of damage, the following mechanisms can be distinguished:
- Acute cytotoxic liver damage
These are characterized by cell death ( necrosis ), which can lead to liver cirrhosis or by heavy deposits of fat ( fatty liver or steatosis). A typical representative of the substances that act in this way is the α-amanitin of the death cap mushroom.
- Intrahepatic cholestasis
Intrahepatic cholestasis is also called cholestatic or toxic hepatitis . This form of facultative liver damage has been described for numerous medicinal products. Here there are metabolic disorders in the production of bile , while the outflow of bile is unhindered. The cause can be insoluble complexes of toxin and bile acid , which clog the bile ducts, or inhibition of the ATPases , which bring about the membrane transport of the bile acids.
- Vascular liver damage
The toxins attack the veins in the center of the liver lobules . The result is a endophlebitis obliterans . The pyrrolizidine alkaloids can be regarded as typical representatives of these poisons .
