Trichloroethylene-induced formic aciduria in the male C57 Bl/6 mouse

Lock, Edward A.; Keane, P.C.; Rowe, Philip H.; Foster, John R.; Antoine, Daniel J.; Morris, Christopher M.

doi:10.1016/j.tox.2017.01.004

Cited by 8 publications

(3 citation statements)

References 36 publications

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“…Similarly, an animal study indicated a marked formic aciduria following TCE which, after 8 weeks' exposure, did not produce renal injury. Only the increase in NAG suggested that renal damage may occur following longer exposure, while inconsistent findings were found for other renal indicators [24]. However, our study participants with renal dysfunction (NAG > 12 U/g cre.)…”

Section: Discussioncontrasting

confidence: 73%

Urinary Malondialdehyde (MDA) and N-Acetyl-β-D-Glucosaminidase (NAG) Associated with Exposure to Trichloroethylene (TCE) in Underground Water

Lin

Kuo

et al. 2022

Toxics

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Trichloroethylene (TCE) is commonly used in various industries. If wastewater in factories is not effectively treated, the inflow into and subsequent contamination of underground water is likely. Our study assessed the association of exposure to TCE in underground water with oxidative stress and renal tubule damage. We selected 579 residents from areas with underground water contaminated with TCE. Each participant was interviewed via a questionnaire. We also assessed their urinary trichloroacetic acid (TCA) levels by gas chromatography (GC)-FID. Urinary malondialdehyde (MDA) and N-acetyl-β-D-glucosaminidase (NAG) were taken as indicators of oxidative stress and renal tubule damage. We found about 73% of the residents to have consumed underground water. The average duration of consumption was 26 years, with an average of 1.6 L per day. Currently, only 1.5% of the residents still continuously consume underground water. The consumption of underground water positively correlated with heightened urinary TCA levels (r = 0.554). Heightened urinary TCA levels, in turn, were positively associated with NAG levels (r = 0.180) but negatively associated with MDA levels (r = −0.193). The results held even after we had segmented urinary TCA levels into three groups of different levels. The elimination of the source of heightened TCE levels from various industrial effluents is essential. Residents exposed to TCE-laden underground water should periodically undergo health inspections.

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Section: Discussioncontrasting

confidence: 73%

Urinary Malondialdehyde (MDA) and N-Acetyl-β-D-Glucosaminidase (NAG) Associated with Exposure to Trichloroethylene (TCE) in Underground Water

Lin

Kuo

et al. 2022

Toxics

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“…To date, there is no consensus on TCOH-induced kidney toxicity, but it may be resulting through perturbation of formate metabolism. The oxidative metabolites of TCE, TCA and TCOH, are known to mediate formic aciduria in rats (Yaqoob et al 2013) and mice (Lock et al 2017). It was also reported that TCE, but not TCOH, can induce elevated renal injury markers in rats after 12 weeks of exposure (Yaqoob et al 2014), even though both chemicals can cause formic aciduria in rats and mice.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains

et al. 2018

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Trichloroethylene (TCE) and tetrachloroethylene (PCE) are structurally similar chemicals that are metabolized through oxidation and glutathione conjugation pathways. Both chemicals have been shown to elicit liver and kidney toxicity in rodents and humans; however, TCE has been studied much more extensively in terms of both metabolism and toxicity. Despite their qualitative similarities, quantitative comparison of tissue- and strain-specific metabolism of TCE and PCE has not been performed. To fill this gap, we conducted a comparative toxicokinetic study where equimolar single oral doses of TCE (800 mg/kg) or PCE (1000 mg/kg) were administered to male mice of C57BL/6J, B6C3F1/J, and NZW/LacJ strains. Samples of liver, kidney, serum, brain, and lung were obtained for up to 36 h after dosing. For each tissue, concentrations of parent compounds, as well as their oxidative and glutathione conjugation metabolites were measured and concentration-time profiles constructed. A multi-compartment toxicokinetic model was developed to quantitatively compare TCE and PCE metabolism. As expected, the flux through oxidation metabolism pathway predominated over that through conjugation across all mouse strains examined, it is 1,200-3,800 fold higher for TCE and 26-34 fold higher for PCE. However, the flux through glutathione conjugation, albeit a minor metabolic pathway, was 21-fold higher for PCE as compared to TCE. The degree of inter-strain variability was greatest for oxidative metabolites in TCE-treated and for glutathione conjugation metabolites in PCE-treated mice. This study provides critical data for quantitative comparisons of TCE and PCE metabolism, and may explain the differences in organ-specific toxicity between these structurally similar chemicals.

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“…Furthermore, cysteine conjugate beta-lyase ( CCBL ) was found to be closely associated with the development of kidney cancer. Studies have shown that variants in the CCBL2 gene were significantly associated with the risk of chronic kidney disease due to a defect in reductive metabolism that leads to the formation of a cysteine conjugate, which is then converted to an active metabolite [ 20 , 22 , 23 ]. The findings piqued our curiosity in the role of the CCBL family member, CCBL2 , in breast tissues, as well as the unknown association between CCBL2 and BC, which is now the most frequently diagnosed cancer worldwide.…”

Section: Introductionmentioning

confidence: 99%

Cysteine conjugate beta-lyase 2 (CCBL2) expression as a prognostic marker of survival in breast cancer patients

Meng

Yang

et al. 2022

PLoS ONE

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Objective Cysteine conjugate beta-lyase 2 (CCBL2), also known as kynurenine aminotransferase 3 (KAT3) or glutamine transaminase L (GTL), plays an essential role in transamination and cytochrome P450. Its correlation with some other cancers has been explored, but breast cancer (BC) not yet. Methods The mRNA and protein expression of CCBL2 in BC cell lines and patient samples were detected by RT-qPCR and immunohistochemistry (IHC). BC patients’ clinical information and RNA-Seq expression were acquired via The Cancer Genome Atlas (TCGA) database. Patients were categorized into high/low CCBL2 expression groups based on the optimal cutoff value (8.973) determined by receiver operating characteristic (ROC) curve. We investigated CCBL2 and clinicopathological characteristics’ relationship using Chi-square tests, estimated diagnostic capacity using ROC curves and drew survival curves using Kaplan–Meier estimate. We compared survival differences using Cox regression and externally validated using Gene Expression Omnibus (GEO) database. We evaluated enriched signaling pathways using gene set enrichment analysis (GSEA), explored CCBL2 and relevant genes’ relationship using tumor immunoassay resource (TIMER) databases and used the human protein atlas (HPA) for pan-cancer analysis and IHC. Results CCBL2 was overexpressed in normal human cell lines and tissues. CCBL2 expression was lower in BC tissues (n = 1104) than in normal tissues (n = 114), validated by GEO database. Several clinicopathologic features were related to CCBL2, especially estrogen receptor (ER), progesterone receptor (PR) and clinical stages. The low expression group exhibited poor survival. CCBL2’s area under curve (AUC) analysis showed finite diagnostic capacity. Multivariate cox-regression analysis indicated CCBL2 independently predicted BC survival. GSEA showed enriched pathways: early estrogen response, MYC and so on. CCBL2 positively correlated with estrogen, progesterone and androgen receptors. CCBL2 was downregulated in most cancers and was associated with their survival, including renal and ovarian cancers. Conclusions Low CCBL2 expression is a promising poor BC survival independent prognostic marker.

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Trichloroethylene-induced formic aciduria in the male C57 Bl/6 mouse

Cited by 8 publications

References 36 publications

Urinary Malondialdehyde (MDA) and N-Acetyl-β-D-Glucosaminidase (NAG) Associated with Exposure to Trichloroethylene (TCE) in Underground Water

Urinary Malondialdehyde (MDA) and N-Acetyl-β-D-Glucosaminidase (NAG) Associated with Exposure to Trichloroethylene (TCE) in Underground Water

Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains

Cysteine conjugate beta-lyase 2 (CCBL2) expression as a prognostic marker of survival in breast cancer patients

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