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[Methods of in vitro evaluation for nephrotoxicity]
N Castaing1, D Merlet, J Cambar
1Groupe d'Etude de Physiologie et Physiopathologie Rénales, Faculté de Pharmacie, Bordeaux.
Abstract:
Mechanisms and precise targets of nephrotoxicants have been evidenced in experimental animals, a very important contribution for decades. But, structural and functional heterogeneity in renal tissue makes often difficult the exact determination of the molecular targets at renal cell level. Indeed, some new in vitro models have been gradually reported. This non exhaustive review purposes to present the different recent models, ever more reductionist, as isolated kidneys, kidney slices, isolated renal cells or renal cultured cells to assess the nephrotoxicity of new molecules. For every model are presented a brief history, the principle of the technique, viability criteria and its relative interest for renal toxicology. In conclusion, a general discussion points out the main advantages and limits of each one.
Insights
This review explores advanced in vitro models for assessing kidney toxicity, overcoming challenges posed by renal tissue complexity. These models aid in identifying molecular targets of nephrotoxicants more precisely.
Area of Science:
- * Renal toxicology and molecular pharmacology.
- * In vitro model development and validation.
Context:
- * Traditional animal models for nephrotoxicant studies face limitations due to renal tissue heterogeneity.
- * Identifying precise molecular targets of kidney toxicants at the cellular level remains challenging.
- * Advancements in in vitro techniques offer more reductionist approaches.
Purpose:
- * To review and present recent, increasingly reductionist in vitro models for assessing nephrotoxicity.
- * To cover models including isolated kidneys, kidney slices, isolated renal cells, and cultured renal cells.
- * To evaluate the utility of these models in identifying molecular targets of novel molecules.
Summary:
- * Discusses the historical development and principles of various in vitro renal models.
- * Details viability criteria and the specific advantages of each model for renal toxicology.
- * Presents a comparative analysis of isolated kidneys, kidney slices, isolated cells, and cell cultures.
- * Highlights the relative merits and limitations of each model in assessing molecule-induced kidney damage.
Impact:
- * Provides a comprehensive overview of current in vitro methodologies for nephrotoxicity assessment.
- * Facilitates the selection of appropriate models for evaluating the renal safety of new chemical entities.
- * Contributes to a better understanding of molecular mechanisms underlying drug-induced kidney injury.