Subchronic Oral Toxicity Study of Furan in B6C3F1 Mice

Gill, Santokh; Kavanagh, Meghan; Barker, Michael; Weld, Madeline M.; Vavasour, Elizabeth; Hou, Yang-Xun; Cooke, Gerard M.

doi:10.1177/0192623311412980

Cited by 36 publications

(47 citation statements)

References 27 publications

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“…The histopathological studies indicate that inflammation occurs during both treatment regimens and is associated with necrotic areas within the liver. These results are consistent with those in other reports [18,19,44]. Our findings are also consistent with previous reports indicating that several weeks of treatment with carcinogenic doses of furan up-regulated genes related to oxidative stress, inflammation and DNA-damage responses in mouse liver [20,45].…”

Section: Discussionsupporting

confidence: 94%

Mutagenicity of furan in female Big Blue B6C3F1 mice

Terrell

Huynh

Grill

et al. 2014

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Furan is an abundant food and environmental contaminant that is a potent liver carcinogen in rodent models. To determine if furan is genotoxic in vivo, female B6C3F1 Big Blue transgenic mice were treated with 15 mg/kg bw furan by gavage 5 days a week for 6 weeks, or once weekly for 3 weeks. Liver cII trans-gene mutation-frequency and mutation spectra were determined. Furan did not increase the mutation frequency under either treatment condition. In the 6-week treatment regimen, there was a change in the cII transgene mutation-spectrum, with the fraction of GC to AT transitions significantly reduced. The only other significant change was an increase in GC to CG transversions; these represented a minor contribution to the overall mutation spectrum. A much larger furan-dependent shift was observed in the 3-week study. There was a significant increase in transversion mutations, predominantly GC to TA transversions as well as smaller non-significant changes in GC to CG and AT to TA transversions. To determine if these mutations were caused by cis-2-butene-1,4-dial (BDA), a reactive metabolite of furan, the mutagenic activity and the mutation spectrum of BDA was determined in vitro, in Big Blue mouse embryonic fibroblasts. This compound did not increase the cII gene mutation-frequency but caused a substantial increase in AT to CG transversions. This increase, however, lost statistical significance when adjusted for multiple comparisons. Together, these findings suggest that BDA may not be directly responsible for the in-vivo effects of furan on mutational spectra. Histopathological analysis of livers from furan-treated mice revealed that furan induced multifocal, hepatocellular necrosis admixed with reactive leukocytes and pigment-laden Kupffer cells, enhanced oval-cell hyperplasia, and increased hepatocyte mitoses, some of which were atypical. An indirect mechanism of genotoxicity is proposed in which chronic toxicity followed by inflammation and secondary cell proliferation triggers cancer development in furan-exposed rodents.

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Section: Discussionsupporting

confidence: 94%

Mutagenicity of furan in female Big Blue B6C3F1 mice

Terrell

Huynh

Grill

et al. 2014

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…There are many studies which have indicated that furan treatment could induce biochemical and physiological dysfunctions in animals and humans (Ajiboye et al in press;Gill et al 2011). Determination of the renal excretion of the waste compounds has supplied useful data on the health status of the kidneys (Tootian et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Furan intake worldwide in which mean intake in European countries was estimated at 0.27-1.17 mg/kg bw/day (Churchwell et al 2015). In foods, the presence of furan is a toxicological concern because high doses of furan are toxic to organs like liver in animals (Gill et al 2011). It was reported to mediate its toxicity in animals by inducing oxidative stress (Ajiboye et al in press).…”

Section: Introductionmentioning

confidence: 99%

Lycopene Protects the Diabetic Rat Kidney Against Oxidative Stress-mediated Oxidative Damage Induced by Furan

Pandır

Ünal

Baş

2016

Braz. arch. biol. technol.

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Furan is a food and environmental contaminant and a potent carcinogen in animals. Lycopene is one dietary carotenoid found in fruits such as tomato, watermelon and grapefruit. The present study was designed to explore the protective effect of lycopene against furan-induced oxidative damage in streptozotocin (STZ)-induced diabetic rat kidney. At the end of the experimental period (28 days), we found that lycopene markedly decreased the malondialdehide (MDA) levels in the kidney, urea, uric acid and creatinine levels in the serum of furan-treated rats. The increase of histopathology in the kidney of furan-treated rats were effectively suppressed by lycopene. Furthermore, lycopene markedly restored superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities in the kidney of furan-treated rats.In conclusion, these results suggested that lycopene could protect the rat kidney against furan-induced injury by improving renal function, attenuating histopathologic changes, reducing MDA production and renewing the activities of antioxidant enzymes.

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“…Changes in thymic lymphocyte subpopulations at the furan highest dose (8 mg/kg body weight ) suggested possible effects of this compound on the immune system (Gill et al, ). In the other words, thymic lymphocyte subpopulations shifting toward decline in CD4+CD8+ cells and a corresponding increase in all other populations of thymocytes including CD4‐CD8‐, CD4+CD8‐, and CD4‐CD8+ could be as a result to furan exposure (Alam, Zeid, Abu, & Imam, ; Baş, Pandır, & Kalender, ; Gill et al, ). Recent studies proposed that antioxidants may play an important role to ameliorate toxic effects of furan (El‐Akabawy & El‐Sherif, ).…”

Section: Review Of Furan Toxicitymentioning

confidence: 99%

Industrial furan and its biological effects on the body systems

et al. 2018

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Furan as a product of thermal processing is found in many foods and beverages. In vitro and in vivo genotoxicity was positive for furan, also when metabolic preconditions for the formation of Z‐2‐butene‐1,4dialdehyde (BDA), the reactive compound, was met. However, in major studies, high doses represented the genotoxic effect. Moreover, data on toxicity in different cells and organs are inconsistent. For preparing remarkable risk assessments in human, providing bioassay data is necessary. We aimed to review available evidences about furan and BDA. A vast number of studies have been published on toxicity of furan in vitro and in vivo. Thus, we present a comprehensive review on the current status of furan in inducing toxic effects in different body systems, and possible mechanisms involved in the negative effects of this compound. In this article, furan mitigation procedures in foods have been taken into account. Practical applications From industrial point, furan is repeatedly used as an intermediate chemical in the process of producing some compounds such as resins, lacquers, pesticides and drugs. Furthermore, it is common as a side‐product of high‐energy radiation and thermal processes in food production. The current study focused on the effects of furan on the body organs. Furthermore, furan mitigation procedures in foods have been addressed in the current study. Nearly all previous studies on the industrial furan demonstrated that it has adverse health effects on the organs of the body. In order to prove specific results, further studies regarding furan risk assessment is of great importance.

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Subchronic Oral Toxicity Study of Furan in B6C3F1 Mice

Cited by 36 publications

References 27 publications

Mutagenicity of furan in female Big Blue B6C3F1 mice

Mutagenicity of furan in female Big Blue B6C3F1 mice

Lycopene Protects the Diabetic Rat Kidney Against Oxidative Stress-mediated Oxidative Damage Induced by Furan

Industrial furan and its biological effects on the body systems

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