Effects of 2-MCPD on oxidative stress in different organs of male mice

Schultrich, Katharina; Henderson, Colin J.; Buhrke, Thorsten; Braeuning, Albert

doi:10.1016/j.fct.2020.111459

Cited by 5 publications

(1 citation statement)

References 21 publications

(42 reference statements)

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“…Strikingly, these studies identified a previously unreported induction of oxidative stress in the brain. 14,15 Importantly, the effects of 2-MCPD, which has not been studied in carcinogenicity studies, were less pronounced, suggesting that the molecular toxicity mechanisms of 2-MCPD and 3-MCPD are potentially different. 14,15 A similar approach was used to demonstrate the capacity of the food preservative ethoxyquin to induce liver toxicity, using a combination of our hGSTP1 and NRF2-nulled reporter mice.…”

Section: Resultsmentioning

confidence: 99%

Potential of in vivo stress reporter models to reduce animal use and provide mechanistic insights in toxicity studies

et al. 2022

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Chemical risk assessment ensures protection from the toxic effects of drugs and manmade chemicals. To comply with regulatory guidance, studies in complex organisms are required, as well as mechanistic studies to establish the relevance of any toxicities observed to man. Although in vitro toxicity models are improving, in vivo studies remain central to this process. Such studies are invariably time-consuming and often involve large numbers of animals. New regulatory frameworks recommend the implementation of “smart” in vivo approaches to toxicity testing that can effectively assess safety for humans and comply with societal expectations for reduction in animal use. A major obstacle in reducing the animals required is the time-consuming and complexity of the pathological endpoints used as markers of toxicity. Such endpoints are prone to inter-animal variability, subjectivity and require harmonisation between testing sites. As a consequence, large numbers of animals per experimental group are required. To address this issue, we propose the implementation of sophisticated stress response reporter mice that we have developed. These reporter models provide early biomarkers of toxic potential in a highly reproducible manner at single-cell resolution, which can also be measured non-invasively and have been extensively validated in academic research as early biomarkers of stress responses for a wide range of chemicals at human-relevant exposures. In this report, we describe a new and previously generated models in our lab, provide the methodology required for their use and discuss how they have been used to inform on toxic risk. We propose our in vivo approach is more informative (refinement) and reduces the animal use (reduction) compared to traditional toxicity testing. These models could be incorporated into tiered toxicity testing and used in combination with in vitro assays to generate quantitative adverse outcome pathways and inform on toxic potential.

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Section: Resultsmentioning

confidence: 99%

Potential of in vivo stress reporter models to reduce animal use and provide mechanistic insights in toxicity studies

et al. 2022

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Boric Acid and Borax Protect Human Lymphocytes from Oxidative Stress and Genotoxicity Induced by 3-Monochloropropane-1,2-diol

Turkez,

Tozlu,

Arslan

et al. 2024

Biol Trace Elem Res

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Abstract3-chloro-1,2-propanediol (3-MCPD) is a member of the group of pollutants known as chloropropanols and is considered a genotoxic carcinogen. Due to the occurrence of 3-MCPD, which cannot be avoided in multiplexed food processes, it is necessary to explore novel agents to reduce or prevent the toxicity of 3-MCPD. Many recent studies on boron compounds reveal their superior biological roles such as antioxidant, anticancer, and antigenotoxic properties. In the current investigation, we have evaluated in vitro cytotoxic, oxidative, and genotoxic damage potential of 3-MCPD on human whole blood cultures and the alleviating effect of boric acid (BA) and borax (BX) for 72 h. In our in vitro experiments, we have treated blood cells with BA and BX (2.5, 5, and 10 mg/L) and 3-MCPD (at IC50 of 11.12 mg/l) for 72 h to determine the cytotoxic damage potential by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH) release assays. Oxidative damage was assessed using total antioxidant capacity (TAC) and malondialdehyde (MDA) levels. Genotoxicity evaluations were performed using chromosome aberrations (CAs) and 8-hydroxy deoxyguanosine (8-OHdG) assays. The result of our experiments showed that the 3-MCPD compound induced cytotoxicity, oxidative stress, and genotoxicity in a clear concentration-dependent manner. BA and BX reduced cytotoxicity, oxidative stress, and genotoxicity induced by 3-MCPD. In conclusion, BA and BX are safe and non-genotoxic under the in vitro conditions and can alleviate cytotoxic, oxidative, and genetic damage induced by 3-MCPD in the human blood cells. Our findings suggest that dietary boron supplements may offer a novel strategy for mitigating hematotoxicity induced by xenobiotics, including 3-MCPD.

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Newly discovered developmental and ovarian toxicity of 3-monochloro-1,2-propanediol in Drosophila melanogaster and cyanidin-3-O-glucoside's protective effect

Cai

Liu

Gao

et al. 2023

Science of The Total Environment

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Effects of 2-MCPD on oxidative stress in different organs of male mice

Cited by 5 publications

References 21 publications

Potential of in vivo stress reporter models to reduce animal use and provide mechanistic insights in toxicity studies

Potential of in vivo stress reporter models to reduce animal use and provide mechanistic insights in toxicity studies

Boric Acid and Borax Protect Human Lymphocytes from Oxidative Stress and Genotoxicity Induced by 3-Monochloropropane-1,2-diol

Newly discovered developmental and ovarian toxicity of 3-monochloro-1,2-propanediol in Drosophila melanogaster and cyanidin-3-O-glucoside's protective effect

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