A critical review of adverse effects to the kidney: mechanisms, data sources, and in silico tools to assist prediction.
Expert Opin Drug Metab Toxicol
; 14(12): 1225-1253, 2018 Dec.
Article
in En
| MEDLINE
| ID: mdl-30345815
ABSTRACT
INTRODUCTION:
The kidney is a major target for toxicity elicited by pharmaceuticals and environmental pollutants. Standard testing which often does not investigate underlying mechanisms has proven not to be an adequate hazard assessment approach. As such, there is an opportunity for the application of computational approaches that utilize multiscale data based on the Adverse Outcome Pathway (AOP) paradigm, coupled with an understanding of the chemistry underpinning the molecular initiating event (MIE) to provide a deep understanding of how structural fragments of molecules relate to specific mechanisms of nephrotoxicity. Aims covered The aim of this investigation was to review the current scientific landscape related to computational methods, including mechanistic data, AOPs, publicly available knowledge bases and current in silico models, for the assessment of pharmaceuticals and other chemicals with regard to their potential to elicit nephrotoxicity. A list of over 250 nephrotoxicants enriched with, where possible, mechanistic and AOP-derived understanding was compiled. Expert opinion Whilst little mechanistic evidence has been translated into AOPs, this review identified a number of data sources of in vitro, in vivo, and human data that may assist in the development of in silico models which in turn may shed light on the interrelationships between nephrotoxicity mechanisms.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug-Related Side Effects and Adverse Reactions
/
Environmental Pollutants
/
Kidney
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Expert Opin Drug Metab Toxicol
Journal subject:
METABOLISMO
/
TOXICOLOGIA
Year:
2018
Document type:
Article
Affiliation country:
United kingdom