Objective:This review aims to investigate and establish potential in vitro and in vivo models for evaluating the anti-urolithiatic activity of therapeutic agents,exploring experimental approaches that can reliably sim...Objective:This review aims to investigate and establish potential in vitro and in vivo models for evaluating the anti-urolithiatic activity of therapeutic agents,exploring experimental approaches that can reliably simulate human stone formation and effectively assess the efficacy of anti-urolithiatic compounds.Methods:Multiple in vitro and in vivo approaches were explored.In vitro methods included the estimation of calcium oxalate by titrimetry,nucleation assays,aggregation assays,turbidimetric assays,and electron microscopy studies.Artificial stone models such as BegoStone and Ultracal 30 were fabricated to mimic the physicochemical characteristics of urinary calculi.In vivo models included ethylene glycol-induced,calcium oxalate/ammonium oxalate-induced,diet-induced,and infection-related models in rodents.Additionally,genetically modified animal models such as TRPV5 knockout,CLDN14 knockout,AGXT knockout,and URAT1 overexpression mice were discussed to study molecular pathways of urolithiasis.Parameters such as urinary oxalate,calcium levels,and histopathological evaluation of kidney tissues were used to validate stone formation and dissolution processes.Results:In vitro models effectively demonstrate the processes of crystal nucleation,aggregation,and inhibition,allowing quantitative assessment of potential anti-urolithiatic activity.Electron microscopy provides detailed insights into crystal morphology and ultrastructural alterations.Artificial stones fabricated using BegoStone and Ultracal 30 closely replicate natural calculi hardness and composition,making them suitable for lithotripsy and dissolution studies.In vivo models successfully mimic human urolithiasis pathophysiology,particularly the ethylene glycol-induced rat model,which shows reproducible calcium oxalate crystal deposition in renal tissues.The application of genetic models highlights the role of specific transporters and enzymes in calcium and oxalate homeostasis.Conclusion:A combination of in vitro and in vivo experimental models provides a comprehensive platform for evaluating the anti-urolithiatic potential of therapeutic agents.The integration of biochemical,morphological,and genetic analyses enhances the understanding of stone pathogenesis and development of novel anti-urolithiatic therapies.展开更多
文摘Objective:This review aims to investigate and establish potential in vitro and in vivo models for evaluating the anti-urolithiatic activity of therapeutic agents,exploring experimental approaches that can reliably simulate human stone formation and effectively assess the efficacy of anti-urolithiatic compounds.Methods:Multiple in vitro and in vivo approaches were explored.In vitro methods included the estimation of calcium oxalate by titrimetry,nucleation assays,aggregation assays,turbidimetric assays,and electron microscopy studies.Artificial stone models such as BegoStone and Ultracal 30 were fabricated to mimic the physicochemical characteristics of urinary calculi.In vivo models included ethylene glycol-induced,calcium oxalate/ammonium oxalate-induced,diet-induced,and infection-related models in rodents.Additionally,genetically modified animal models such as TRPV5 knockout,CLDN14 knockout,AGXT knockout,and URAT1 overexpression mice were discussed to study molecular pathways of urolithiasis.Parameters such as urinary oxalate,calcium levels,and histopathological evaluation of kidney tissues were used to validate stone formation and dissolution processes.Results:In vitro models effectively demonstrate the processes of crystal nucleation,aggregation,and inhibition,allowing quantitative assessment of potential anti-urolithiatic activity.Electron microscopy provides detailed insights into crystal morphology and ultrastructural alterations.Artificial stones fabricated using BegoStone and Ultracal 30 closely replicate natural calculi hardness and composition,making them suitable for lithotripsy and dissolution studies.In vivo models successfully mimic human urolithiasis pathophysiology,particularly the ethylene glycol-induced rat model,which shows reproducible calcium oxalate crystal deposition in renal tissues.The application of genetic models highlights the role of specific transporters and enzymes in calcium and oxalate homeostasis.Conclusion:A combination of in vitro and in vivo experimental models provides a comprehensive platform for evaluating the anti-urolithiatic potential of therapeutic agents.The integration of biochemical,morphological,and genetic analyses enhances the understanding of stone pathogenesis and development of novel anti-urolithiatic therapies.
