Pharmacokinetics and bioavailability of oral single-dose maleic acid in biofluids of Sprague-Dawley rats

Wu, Chunchi; Chen, Hsin‐Chang; Luo, Yu‐Syuan; Chiang, Su‐Yin; K, Wu

doi:10.1016/j.dmpk.2016.09.005

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…Our targeted analysis revealed that significantly elevated urinary levels of 8-OHdG and 8-NO 2 Gua were observed as early as within 12 hours after MA consumption; while statistically meaningful increases in 8-isoPGF 2 α were witnessed within 24 hours. Both phenomena correspond with the rapid absorption and elimination of MA demonstrated in established reports (Hou, Lu, Lin, Lin, & Tsai, 2016;Wu et al, 2016a). Additionally, our results revealed that MA triggers oxidant and nitrosant attacks; such stress could lead to cellular or tissue damage in the kidneys and liver, as supported by our histological observations of undefined glomerular cells, disorderly arrangement of the tubular epithelial cell vacuoles and renal tubules.…”

Section: Oxidative Stress Inflammation and Lipid Peroxidationsupporting

confidence: 89%

Nuclear magnetic resonance‐ and mass spectrometry‐based metabolomics to study maleic acid toxicity from repeated dose exposure in rats

Chen

et al. 2017

J of Applied Toxicology

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Maleic acid (MA), a chemical intermediate used in many consumer and industrial products, was intentionally adulterated in a variety of starch-based foods and instigated food safety incidents in Asia. We aim to elucidate possible mechanisms of MA toxicity after repeated exposure by (1) determining the changes of metabolic profile using H nuclear magnetic resonance spectroscopy and multivariate analysis, and (2) investigating the occurrence of oxidative stress using liquid chromatography tandem mass spectrometry by using Sprague-Dawley rat urine samples. Adult male rats were subjected to a 28 day subchronic study (0, 6, 20 and 60 mg kg ) via oral gavage. Urine was collected twice a day on days 0, 7, 14, 21 and 28; organs underwent histopathological examination. Changes in body weight and relative kidney weights in medium- and high-dose groups were significantly different compared to controls. Morphological alterations were evident in the kidneys and liver. Metabolomic results demonstrated that MA exposure increases the urinary concentrations of 8-hydroxy-2'-deoxyguanosine, 8-nitroguanine and 8-iso-prostaglandin F ; levels of acetoacetate, hippurate, alanine and acetate demonstrated time- and dose-dependent variations in the treatment groups. Findings suggest that MA consumption escalates oxidative damage, membrane lipid destruction and disrupt energy metabolism. These aforementioned changes in biomarkers and endogenous metabolites elucidate and assist in characterizing the possible mechanisms by which MA induces nephro- and hepatotoxicity.

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Section: Oxidative Stress Inflammation and Lipid Peroxidationsupporting

confidence: 89%

Nuclear magnetic resonance‐ and mass spectrometry‐based metabolomics to study maleic acid toxicity from repeated dose exposure in rats

Chen

et al. 2017

J of Applied Toxicology

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“…Previously, our group published the pharmacokinetic study of MA upon oral administration [ 8 ]. In that study, MA is rapidly absorbed and metabolized upon consumption, with the majority of administered dose excreted through urine.…”

Section: Discussionmentioning

confidence: 99%

“…To achieve detection of low concentrations of MA, advances in analytical methods with LC-MS/MS and Near-Infrared (NIR) spectroscopy and chemometrics were reached to attain high sensitivity and specificity [ 6 , 7 ]. Improvements in these methods furthered our understanding of the pharmacokinetic behavior and can also assist in investigating the toxicological implications of MA from consumption [ 8 – 10 ]. However, most of the toxic effects occur at the cellular and tissue levels.…”

Section: Introductionmentioning

confidence: 99%

Elevation in and persistence of multiple urinary biomarkers indicative of oxidative DNA stress and inflammation: Toxicological implications of maleic acid consumption using a rat model

Chen

et al. 2017

PLoS ONE

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Maleic acid (MA), an intermediate reagent used in many industrial products, instigated public health concerns in Taiwan when it was used to adulterate an array of starch-based delicacies to improve texture and storage time. Established studies reported that exposure to high concentrations of MA induce renal injury; little is known whether oxidative stress is induced at a relative low dose. This study aims to investigate the effect of oral single dose exposure of MA on the status of oxidative stress and inflammation. Single dose of MA at 0, 6 and 60 mg/kg (control, low- and high-dose groups, respectively) were orally administered to adult male and female rats. Urine samples were collected and analyzed to measure 8-hydroxy-2’-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-IsoPGF2α), 8-nitroguanine (8-NO2Gua) and N-acetyl-S-(tetrahydro-5-hydroxy-2-pentyl-3-furanyl)-L-cysteine (HNE-MA) using LC-MS/MS. Results revealed that oral consumption of MA induced oxidative DNA damage and lipid peroxidation, as demonstrated by the statistically significant increases in urinary levels of 8-NO2Gua, 8-OHdG, and 8-isoPGF2α, in high-dosed male rats within 12 h of oral gavage (p < 0.05). Additionally, increases in concentration of these biomarkers persist for days after consumption; male rats appear to be more sensitive to oxidative burden compared to their counterparts. The aforementioned findings could help elucidate the mechanisms through which nephrotoxicity occur.

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“…Additives, with relatively low molecular weight and high reactivity, are easier to migrate and may have higher safety risks. Long-term exposure of maleic anhydride, which is commonly used in PPCs, will cause certain damage to the respiratory system, digestive system, and kidney [71,72]. Many countries and regions have also set a migration limit for this substance [73,74].…”

Section: Additivesmentioning

confidence: 99%

Safety Risks of Plant Fiber/Plastic Composites (PPCs) Intended for Food Contact: A Review of Potential Hazards and Risk Management Measures

Zhang

Weng

2021

Toxics

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Plant fiber/plastic composites (PPCs), with the benefits of low cost and easy processing, have been widely used in the production of various food contact products. They are generally considered to be economical and environmentally friendly because of their natural raw materials (plant fibers) and recommended to be one of the ideal alternatives to traditional petrochemical-based plastics. However, in addition to plastic resins and plant fibers, some indispensable additives are involved in the production process of PPCs, which may pose food safety risks. To date, excessive migration of hazardous substances (such as melamine) has been reported in some products made of PPCs, and the safety and applicability of PPCs as food contact materials need to be further studied. In this paper, the main raw materials of PPCs used for food contact are taken as the pointcut to analyze the possible hazards, sources of hazards, and existing risk management measures in various countries. The conclusion shows that PPCs used for food contact may have potential safety risks at present. However, systematic research on migration methods and safety assessment are still insufficient, and further studies are needed regarding the main safety risks and migration patterns.

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Pharmacokinetics and bioavailability of oral single-dose maleic acid in biofluids of Sprague-Dawley rats

Cited by 5 publications

References 29 publications

Nuclear magnetic resonance‐ and mass spectrometry‐based metabolomics to study maleic acid toxicity from repeated dose exposure in rats

Nuclear magnetic resonance‐ and mass spectrometry‐based metabolomics to study maleic acid toxicity from repeated dose exposure in rats

Elevation in and persistence of multiple urinary biomarkers indicative of oxidative DNA stress and inflammation: Toxicological implications of maleic acid consumption using a rat model

Safety Risks of Plant Fiber/Plastic Composites (PPCs) Intended for Food Contact: A Review of Potential Hazards and Risk Management Measures

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