Idiosyncratic drug-induced liver injury and the role of inflammatory stress with an emphasis on an animal model of trovafloxacin hepatotoxicity.
Idiosyncratic adverse drug reactions (IADRs) occur in a minority of patients yet account for the majority of postmarketing use restrictions by the Food and Drug Administration. Despite the impact of these toxicities, the underlying mechanisms are still poorly understood. Animal models of IADRs would be beneficial in understanding mechanisms and in developing assays with predictive potential. Recent work exploring the interactions between inflammatory stress and drugs associated with human idiosyncratic drug-induced liver injury (IDILI) has led to the development of the first animal models that apply to a range of drugs. Here, we discuss hypotheses for the mechanisms of IDILI and focus on a murine model of trovafloxacin-induced hepatotoxicity as an example related to the inflammatory stress hypothesis.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38104, USA.
Patrick J
PJ
Shaw
Patricia E
PE
Ganey
Robert A
RA
Roth
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology* / Q000378:metabolism; D024841:Fluoroquinolones / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D009287:Naphthyridines / Q000633:toxicity*; D013312:Stress, Physiological / Q000502:physiology
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin