3.2. Mechanisms of hepatotoxicity

The hepatocytes, cholangiocytes, Kupffer cells, ductal and endothelial cells are involved in the mechanisms by which drugs cause hepatotoxicity [28]; having direct effects on cellular organelles such as mitochondria, endoplasmic reticulum, cytoskeleton, microtubules or nucleus.

The drug metabolites generated in the liver through biotransformation can cause hepatic damage because formation of toxic or reactive substances such as electrophilic chemicals or free radicals [29], and thus an unchain a variety of chemical reactions may happen. These mechanisms can either generate necrosis or apoptosis or both. The following are some of the main mechanisms of liver injury [30]:

• Mitochondrial dysfunction: may be generated by the disruption of β-oxidation of lipids and oxidative energy production within the hepatocytes. Mitochondrial membrane permeabilization can lead to apoptosis, a rupture in mitochondrial membrane can lead to ATP depletion and subsequent necrosis, and an abnormal function can also lead to fat accumulation, so steatosis can be present [31].

