Assessment of osteopontin as an early nephrotoxicity indicator in human renal proximal tubule cells and its application in evaluating lanthanum-induced nephrotoxicity

Autor: Yingsi Chen, Feifei Xu, Xiaoxuan Xiao, Huiqin Chi, Yuefei Lai, Xiuqin Lin, Qiuyun Li, Jia Song, Weiliang Wu, Ziyin Li, Xingfen Yang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Ecotoxicology and Environmental Safety, Vol 271, Iss , Pp 115928- (2024)
Druh dokumentu: article
ISSN: 0147-6513
DOI: 10.1016/j.ecoenv.2024.115928
Popis: Nephrotoxicity is a common adverse effect induced by various chemicals, necessitating the development of reliable toxicity screening models for nephrotoxicity assessment. In this study, we assessed a group of nephrotoxicity indicators derived from different toxicity pathways, including conventional endpoints and kidney tubular injury biomarkers such as clusterin (CLU), kidney injury molecule-I (KIM-1), osteopontin (OPN), and neutrophil gelatinase-associated lipocalin (NGAL), using HK-2 and induced pluripotent stem cells (iPSCs)-derived renal proximal tubular epithelial-like cells (PTLs). Among the biomarkers tested, OPN emerged as the most discerning and precise marker. The predictive potential of OPN was tested using a panel of 10 nephrotoxic and 5 non-nephrotoxic compounds. The results demonstrated that combining OPN with the half-maximal inhibitory concentration (IC50) enhanced the diagnostic accuracy in both cellular models. Additionally, PTLs cells showed superior predictive efficacy for nephrotoxicity compared to HK-2 cells in this investigation. The two cellular models were utilized to evaluate the nephrotoxicity of lanthanum. The findings indicated that lanthanum possesses nephrotoxic properties; however, the degree of nephrotoxicity was relatively low, consistent with the outcomes of in vivo experiments.
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