TAMH: A Useful In Vitro Model for Assessing Hepatotoxic Mechanisms

Table 1

List of compounds investigated in TAMH and their general effects.

Agent	Drug class	Pathways affected	Reference(s)
APAP	Analgesic	(i) ATP depletion; (ii) GSH depletion; (iii) Induces Jnk activation; (iv) Upregulation of ETC protein components; (v) Activation of p53 signaling	[31, 39, 40, 44]
TFEC	N/A; fluorocarbon metabolite	(i) Nrf2 induction and increased expression of ARE response genes; (ii) Induction of ER-stress response genes; (iii) Cell death is Bax-mediated (antagonized by Bcl-xl overexpression); (iv) Upregulation of Hsps	[12, 55, 81]
Flutamide	Antiandrogen	(i) Upregulation of Nrf2 response genes; (ii) Downregulation of fatty acid β-oxidation genes Mitochondrial dysfunction (ATP depletion, complex I inhibition)	[61]
PD035901	MEK inhibitor	(i) Inhibits ERK activation; (ii) Inhibited cell growth	[63]
Lapatinib	Tyrosine kinase inhibitor	(i) Cyp3a induction (dexamethasone) increased cell death	[67]
Flupirtine	Analgesic	(i) Toxicity not directly linked to oxidative processes	[72]