Michel Kranendonk, head of the research group Xenobiotic Metabolism of the Center for Toxicogenomics & Human Health (ToxOmics), one of the research units at CEDOC from NOVA Medical School, has co-authored a recent published review article in the Journal of Hepathology, regarding Drug Induced Liver Injury (DILI), the most frequently occurring form of Adverse Drug Reaction (ADR).
The review highlights emerging in vitro and in vivo pre-clinical models, as well as advanced imaging and in silico technologies, which may improve prediction of clinical outcomes in DILI. One of the more studied compounds regarding DILI is paracetamol, the most common over-the-counter analgesic and antipyretic worldwide, also known as acetaminophen (APAP). Michel says that when there is overdosing with APA, “the capacity of detoxification and excretion routes are overwhelmed, a secondary, highly reactive metabolite accumulates, causing liver damage.”
He continues: “An increased risk for drug induced hepatoxicity occurs in aged persons, consequence of their diminished drug detoxification capacities. Additionally, elderly people often suffer from multiple comorbidities e.g., cardiovascular conditions and diabetes, needing multiple therapeutic treatments. Both diminished drug detoxification capacity and frequently occurring poly-medication of older people makes the elderly particular vulnerable for the development of ADRs such as DILI, an increasing health problem of our aging society. An increase in ADR related hospitalizations and even fatalities has been noticed for this age group, during the last decades”.
The authors also make a point for the inevitable need of animal research: “although several specialized in vitro models are being used, DILI can only be fully understood on the organism level, for which in vivo models are necessary, particularly regarding genetic susceptibility, the role of the environment and comorbidities, in the development of DILI. Multi-scale data integration tools are required in the complementary use of different preclinical models to integrate outcomes. This will enhance our mechanistic knowledge and can identify knowledge gaps and deficits in existing tests and models intended to predict DILI”.
This review is a consensus statement by the European DILI Network [PRO-EURO-DILI-NET], an EU financed COST Action. Michel Kranendonk is part of the Management Committee, as well as member of the Work Group PRECLINICAL EVALUATION OF DILI, of this COST Action.
You can find the full article at Journal of Hepathology here.