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.

Charlene Wu,Shu-Ting Chen,Kuen-Yuh Wu,Hsin-Chang Chen,Su-Yin Chiang

doi:10.1371/journal.pone.0183675

Charlene Wu, Shu-Ting Chen + Show 3 more

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https://doi.org/10.1371/journal.pone.0183675

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Abstract

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.

Highlights

Intentional adulteration of Maleic anhydride (MAH), an organic and multifunctional chemical intermediate used in many fields of applied chemistry, in many foods raised health-related anxiety in both Taiwan and abroad
reactive oxygen species (ROS)/reactive nitrogen species (RNS) in tissues or body fluids due to their high reactivity and extremely short half-lives, this study aims to determine, via LC-MS/MS, whether single-dose exposure of Maleic acid (MA) affects the urinary levels of the four aforementioned biomarkers
The main objective of this study was to use a sensitive and non-invasive analytical method to investigate the effect of MA consumption on the formation of biomarkers indicative of Oxidative stress induced by oral single-dose of maleic acid in rats oxidative stress (8-OHdG), inflammation (8-No2Gua) and lipid peroxidation (8-isoPGF2α and HNE-MA)

Summary

Introduction

Intentional adulteration of Maleic anhydride (MAH), an organic and multifunctional chemical intermediate used in many fields of applied chemistry, in many foods raised health-related anxiety in both Taiwan and abroad. Maleic acid (MA), the hydrolyzed form of MAH, typically. Oxidative stress induced by oral single-dose of maleic acid in rats. The general population is likely to be exposed to MA upon contact from personal care products and through inhalation of dust and aerosols from automobile emissions [2, 3]. The California Environmental Protection Agency estimated the statewide emission rate of MAH from industrial facilities at 3340 kg year-1. Upon dermal contact and via inhalation, MA can irritate the mucous membranes of the eye and the upper respiratory tract, respectively, at as low as 0.25 ppm [4]

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