T10: Liver toxicity

9 important questions on T10: Liver toxicity

What is a fatty liver (steatosis)

This is that your liver tissue is accumulation fat lipoprotein transport or metabolism is disrupted and than fatty acid accumulate.. This is an adverse effect and can come because of alcohol consumption or obesity.

What are causes of a fatty liver?

- insulin resistance (due to obesity
- oversupply of fatty acids
- Interference with triglyceride cycle
- Increased fatty acid synthesis/esterification
- decrease fatty acid oxidation
- Decreased apoprotein synthesis
- Decreased synthesis/secretion of VLDL

What are chemicals that cause liver toxicity?

Acetaminophen and aflatoxin
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What is Hepatocyte death: necrosis & apoptosis

The cells are dying. This could be caused by an overdose of paracetamol.
The function of the tissue is gone when the cells died.

zone 3 is most at risk here

Which types of effect represent adverse effects of chemicals on the liver?

-steatosis
-cholestasis

Toxic effects of chemicals on the liver?

Zone 3 hepatocytes are especially sensitive to chemicals that require bioactivation by cytochromes P450

Liver damage caused by aflatoxin

-mutation of the gene for the p53 tumor suppressor gene plays a role in the mechanism of toxic action resulting can liver cancer
-aflatoxin requires bioctivation before it can can exert its adverse effect on the liver.

What is a liver tumor?

The location of the tumor in the liver will be dependent on if the liver is still functioning or not. There could be tumore where the liver is fine, but also there could be total damage tumors.

What chemicals can result in liver cancer?

Aflatoxins! In mais or grain metabolised by P450. It also has a high affinity to the P53 gene, so it mutates easily.
Androgens
vinylchloride
arsenic
thorium dioxide
unsaturated pyrrolyzidine alkaloids (PAs)
alkenylbenzenes

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