1,3-Dichloro-2-propanol evokes inflammation and apoptosis in BV-2 microglia via MAPKs and NF-κB signaling pathways mediated by reactive oxygen species

Xiao, Changlai; He, Pandi; Han, Jingjing; Tang, Miaoling; Wang, Zhen; Mi, Yashi; Liu, Xuebo

doi:10.1016/j.toxlet.2017.12.011

Cited by 10 publications

(11 citation statements)

References 19 publications

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“…Although it is not clear why a robust KIM-1 signal was not detected on a consistent basis in parallel with the trends observed for the other endpoints, one possible explanation could be that 3-MCPD inhibits the MAPK pathway such that the ability of HK-2 cells to undergo a KIM-1-mediated cell repair process is compromised. This hypothesis is supported by other publications showing that other chloropropanols can indeed modulate MAPK pathways (Liu et al, 2016b;Xiao et al, 2018). Notably, as we measured KIM-1 expression following exposure to the control compounds PMA and VAL in our current study, its levels did rise as expected at low doses of PMA and high doses of VAL, confirming that the assay itself performed as expected.…”

Section: Discussionsupporting

confidence: 92%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 92%

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

et al. 2020

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“…Previous studies revealed that large intake of 3‐MCPD can lead to failure in renal function, male sterility and other pathological reactions (Xiao et al., 2018). Our previous data showed that the kidney is the target organ for the toxicity of 3‐MCPD (Nazari et al., 2020).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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3‐Monochloropropane‐1,2‐diol (3‐MCPD) as a byproduct of food processing and a carcinogenic agent has attracted much attention in the last decades. Kidney is the main target organ that is sensitive to the toxicity of 3‐MCPD. Due to limited evidence about possible 3‐MCPD toxicity, we design an investigation to determine the role of mitochondrial biogenesis following chronic oral administration of 3‐MCPD (2, 4, 8 and 32 mg/kg) for 2 months in male C57 mice. The present study evaluated the affects of 3‐MCPD in modulating metabolic signalling which is associated with Il‐18, PGC‐1α, Nrf‐2 and Sir3 which are the major transcription factors. Our data confirms controversial behaviors after chronic exposure with 3‐MCPD. Over expression of the PGC‐1α and Sir3 and IL‐18 were observed after exposure with 2,4 & 8 mg kg−1 day−1 of 3‐MCPD. In front, PGC‐1α down‐regulation occurs at the highest dose (32 mg/kg) resulted in kidney injury. Based on the findings, PGC‐1α plays an important role in the restoration of the mitochondrial function during the recovery from chronic kidney injury. We suggest that the PGC‐1α can be consider as a therapeutic target in prevention and treatment of kidney injury after chronic exposure of 3‐MCPD. Practical applications 3‐Monochloropropane‐1, 2‐diol (3‐MCPD) existed in several foods, can induce nephrotoxicity, progressive nephropathy and renal tubule dilation following acute and chronic exposure. It revealed that 3‐MCPD toxicity is related to metabolites which can cause oxidative stress and activation of cell death signaling. It seems that cytotoxicity of 3‐MCPD has disruptive effect on kidney cells due to rise in ROS production and decrease in mitochondrial membrane permeability. These effects can lead to MPT pore opening, cytochrome c release and activation of programed cell death signaling pathway. Therefore, present study was investigated the role of PGC‐1a and the metabolic signaling involved in 3‐MCPD‐induced nephrotoxicity for the first time. Our data revealed that up‐regulation of mitochondrial biogenesis following chronic exposure with 3‐MCPD accelerates recovery of mitochondrial and cellular function in kidney by deacetylation of histones, overexpression of transcription factors (PGC‐1α, Nrf‐2, and Sir3) and maintaining cellular homeostasis.

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“…This demonstrated that VEGF and angiogenesis are necessary for bone generation and remodeling, establishing the role of VEGF as a growing area of interest. Further, it was shown that under inflammatory conditions, exposure to orthopedic particles lead to increased VEGF expression both at the mRNA and protein levels [5,28] and regulation of osteoclasts. These studies lend credence to the critical role of VEGF in homeostatic bone generation and regeneration as well as its contribution to inflammatory, particle-induced, osteolysis.…”

Section: Discussionmentioning

confidence: 99%

“…Yang et al were able to show that bone marrow-derived mesenchymal stem cells produced VEGF in response to inflammatory cytokines [29]. Other groups have investigated and shown that osteoblasts, osteoclasts, and neutrophils all can react to or produce VEGF, leading to osteolysis [5]. These wide cellular responses are expected due to the non-specific nature of implant debris action, supporting the notion that orthopedic particles have the potential to elicit angiogenic and pro-inflammatory responses in numerous cell types around the implant site.…”

Section: Discussionmentioning

confidence: 99%

Targeting vascular endothelial growth factor ameliorates PMMA-particles induced inflammatory osteolysis in murine calvaria

Abu‐Amer

Arra

Clohisy

et al. 2019

Bone

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Cytokines and growth factors mediate inflammatory osteolysis in response to particles released from bone implants. However, the mechanism by which this process develops is not entirely clear. Blood vessels and related factors may be required to deliver immune cells and soluble factors to the injury site. Therefore, in the current study we investigated if, vascular endothelial growth factor (VEGF), which is required for angiogenesis, mediates polymethylmethacrylate (PMMA) particles-induced osteolysis. Using bone marrow derived macrophages (BMMs) and ST2 stromal cell line, we show that PMMA particles increase VEGF expression. Further, using a murine calvarial osteolysis model, we found that PMMA injection over calvaria induce significant increase in VEGF expression as well as new vessel formation, represented by von Willebrand factor (vWF) staining. Co-treatment using a VEGF-neutralizing antibody abrogated expression of vWF, indicating decreased angiogenesis. Finally, VEGF neutralizing antibody reduced expression of Tumor necrosis factor (TNF) and decreased osteoclastogenesis induced by PMMA particles in calvariae. This work highlights the significance of angiogenesis, specifically VEGF, as key driver of PMMA particle-induced inflammatory osteolysis, inhibition of which attenuates this response.

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1,3-Dichloro-2-propanol evokes inflammation and apoptosis in BV-2 microglia via MAPKs and NF-κB signaling pathways mediated by reactive oxygen species

Cited by 10 publications

References 19 publications

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

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

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

Targeting vascular endothelial growth factor ameliorates PMMA-particles induced inflammatory osteolysis in murine calvaria

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