A critical review of adverse effects to the kidney: mechanisms, data sources and in silico tools to assist prediction
| Autor: | Steven J. Enoch, Claire L. Mellor, James W. Firman, Steven D. Webb, Julia Pletz, Diviya M. Jais, Gopal Pawar, Judith C. Madden, Carlos Alberto Tagliati, Mark T. D. Cronin |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
RM Drug-Related Side Effects and Adverse Reactions In silico HA B220 Information Storage and Retrieval Toxicology Bioinformatics Kidney Risk Assessment Nephrotoxicity 03 medical and health sciences Medicine Animals Humans Computer Simulation Adverse effect Pharmacology business.industry General Medicine R1 030104 developmental biology medicine.anatomical_structure Toxicity Environmental Pollutants business |
| ISSN: | 1742-5255 1744-7607 |
| Popis: | 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 utilise multi-scale 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.\ud 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.\ud 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 inter-relationships between nephrotoxicity mechanisms. |
| Databáze: | OpenAIRE |
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