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

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.

Investigation of the metabolic difference between ST-elevated myocardial infarction and non-ST-elevated myocardial infarction via LC/Q-TOF/MS/MS

“…Oxidative stress plays an important role in ischemic myocardial injury, and elevated levels of ROS have been detected in ischemic myocardium (Misra et al 2009). Several studies have reported that butyric acid, maleic acid, and malonic acid cause oxidative stress and fumaric acid was an endogenous antioxidant compound (Laborde et al 2014;Maragos et al 2004;Wu et al 2017). Thus, increased butyric acid, maleic acid, and malonic acid and decreased fumaric acid can have an important role in ischemic myocardial injury and may be related to the degree of ischemia.…”

Correction: 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

“…The authors wish to clarify the relationship between this PLOS ONE article (a single-dose study) [ 1 ] and a closely related repeated-dose toxicity study published in July 2017 in the Journal of Applied Toxicology [ 2 ]. Findings discussed in this PLOS ONE article [ 1 ] focus on oxidative stress induction and persistence after single-dose oral (gavage) exposure to maleic acid (MA), elucidating the kinetics of oxidant burden formation and clearance. In the Journal of Applied Toxicology study [ 2 ], the authors investigate the effects of repeated exposure to MA in rats, using 1 H nuclear magnetic resonance analysis to focus on changes in the metabolic profile.…”

“…In fact, the authors found no significant histological changes in liver and kidney tissue at seven days in rats administered a single dose of MA as compared to untreated controls. The authors mention “histopathological observations” in the last sentence of the Discussion in [ 1 ], referring to results of analyses that were not included in the manuscript. The latter part of the last sentence should therefore be omitted.…”