The liver may be exposed to large concentrations of exogenous

substances and their metabolites. Metabolism of exogenous

compounds can modulate the properties of hepatotoxicant by either
increasing its toxicity (toxication or metabolic activation) or decreasing
its toxicity (detoxification)

Another Phase II reaction involves glutathione which can covalently

bind to toxic intermediates by glutathione-Stransferase [20]. As a
result, these reactions are usually considered detoxification pathways.
However, this phase can also lead to the formation of unstable
precursors to reactive species that can cause hepatotoxicity

Various chemicals and metal ions bind to mitochondrial membranes

and enzymes, disrupting energy metabolism and cellular
respiration [6]. Many hepatotoxicants act as direct inhibitors and
uncouplers of mitochondrial electron transport [25]. Covalent binding
of the drug to intracellular proteins cause a decrease in ATP
levels leading to actin disruption and rupture of the
membrane. The mushroom toxin, phalloidin also causes increase in
plasma membrane permeability by binding to actin and disrupting the
cell cytoskeleton [57]. Toxicants like chlorpromazine, phenothiazines,
erythromycin salts and chenodeoxycholate have direct surfactant
effects on the hepatocyte plasma membrane [58]. NAPQI forms a
covalent adduct with mitochondrial proteins having thiol groups and
plasma membrane proteins involved in calcium homeostasis