Long-term <i>in vitro</i> effects of exposing the human HK-2 proximal tubule cell line to 3-monochloropropane-1,2-diol

Abstract

Monochloropropane-1,2-diol (3-MCPD) is a food processing contaminant in the U.S. food supply, detected in infant formula. In vivo rodent model studies have identified a variety of possible adverse outcomes from 3-MCPD exposure including renal effects like increased kidney weights, tubular hyperplasia, kidney tubular necrosis, and chronic progressive nephropathy. Given the lack of available in vivo toxicological assessments of 3-MCPD in humans and the limited availability of in vitro human cell studies, the health effects of 3-MCPD remain unclear. We used in vitro human proximal tubule cells represented by the HK-2 cell line to compare short-and long-term consequences to continuous exposure to this compound. After periodic lengths of exposure (0-100 mM) ranging from 1 to 16 days, we evaluated cell viability, mitochondrial integrity, oxidative stress, and a specific biomarker of proximal tubule injury, Kidney Injury Molecule-1 (KIM-1). Overall, we found that free 3-MCPD was generally more toxic at high concentrations or extended durations of exposure, but that its overall ability to induce cell injury was limited in this in vitro system. Further experiments will be needed to conduct a comprehensive safety assessment in infants who may be exposed to 3-MCPD through consumption of infant formula, as human renal physiology changes significantly during development.

The role of PGC‐1α and metabolic signaling pathway in kidney injury following chronic administration with 3‐MCPD as a food processing contaminant

“…Based on previous studies, chronic exposure with 3‐MCPD is associated with increasing in ROS level, mitochondrial membrane permeability transition pore opening followed by programmed cell death signaling activation (Gao et al., 2017; Mossoba et al., 2020; Zhong et al., 2018). Therefore, following chronic 3‐MCPD exposure, the amount of IL‐18 as an IFN‐γ‐ prompting element, increases in kidney, leading to the adjustment of IL‐18 precursor matured by caspase‐1 (Bhargava & Schnellmann, 2017; Mei et al., 2017).…”