Open AccessElevation in and persistence of multiple urinary biomarkers indicative of oxidative DNA stress and inflammation: Toxicological implications of maleic acid consumption using a rat model
Author(s) -
Chunchi Wu,
HsinChang Chen,
Shu-Ting Chen,
SuYin Chiang,
Wu K
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0183675
Subject(s) - oxidative stress , nephrotoxicity , lipid peroxidation , inflammation , dna damage , deoxyguanosine , urinary system , medicine , physiology , chemistry , urine , pharmacology , endocrinology , toxicology , kidney , biochemistry , biology , dna
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 F 2α (8-IsoPGF 2α ), 8-nitroguanine (8-NO 2 Gua) 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-NO 2 Gua, 8-OHdG, and 8-isoPGF 2α , 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.