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

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.

Geniposide alleviated hydrogen peroxide-induced apoptosis of human hepatocytes via altering DNA methylation.

Geniposide (GP) is the homology of medicine and food with bioactive effects of antioxidation and resistance to apoptosis in the liver. It's of great significance to explore the biosafety exposure limits and action mechanisms of GP. This study detected the global DNA methylation microenvironment and the regulation of specific genes in GP against cellular apoptosis induced by hydrogen peroxide (H2O2) of human hepatocyte L-02 cells. The half inhibitory concentration (IC50) of GP on normal L-02 cells was 57.7 mg/mL. GP exerted new epigenetic activity, increased DNMT1, decreased TET1 and TET2 expression, and reversed the demethylation effect to some extent, thereby increasing the overall genomic DNA methylation level at the concentration of 900 µg/mL. GP pretreatment could also adjust the level of P53, Bcl-2 and AKT altered by H2O2, reducing their specific DNA methylation levels in the promoter regions of AKT and Bcl-2 to inhibit apoptosis. Taken together, GP regulates the global DNA methylation level and controls the expression changes of P53, Bcl-2 and AKT, jointly inhibiting the occurrence of apoptosis in human hepatocytes and providing the newly theoretical references for its safety evaluation.

Bioaccessibility and bioavailability adjusted dietary exposure of cadmium for local residents from a high-level environmental cadmium region.

The critical health risks caused by cadmium (Cd) via dietary exposure are commonly assessed by detecting Cd concentrations in foods. Differently, in this study, the bioaccessibility and bioavailability of Cd in major local harvests were introduced to assess the dietary exposure of local residents from a high-level environmental Cd region. The results indicated that certain Cd was released into the digestive juice after in vitro digestion with a bioaccessibility of 20-63% for rice and 3-32% for leafy vegetables, and the released portion was partially absorbed by Caco-2 cells with a bioavailability of 2-21% for rice and 0.2-13% for leafy vegetables. The results obtained from the toxicokinetic model revealed that the predicted urinary Cd values from the estimated daily intake (EDI) of Cd, which accounted for bioaccessibility and bioavailability, were consistent with the actual measured values, and the EDIs were considerably lower than the acceptable daily intake. This suggests that the bioaccessibility and bioavailability adjusted dietary Cd exposure should be more precise. The key issues addressed in our study implores that a potential health risk cannot be neglected in people with high consumption of rice from high-level zone.