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

<div><p>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-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-isoPGF_2α, in high-dosed male rats within 12 h of oral gavage (<i>p</i> < 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.</p></div

Measurement of Tip Apex Distance and Migration of Lag Screws and Novel Blade Screw Used for the Fixation of Intertrochanteric Fractures - Fig 1

<p>(a) Blade Screw DHS (ODRC Dynamic Hip Screw System, Chin Bone Corp., Taiwan; US FDA 510(k): K103015). (b) Radiographs of an 101 years-old woman showing fixation with a Blade Screw DHS post-operation. (c) The design and components of Blade Screw DHS.</p

Chromatogram of rat urine samples using offline SPE-LC-MS/MS; the quantitation channels are marked with *.

<p>Chromatogram of rat urine samples using offline SPE-LC-MS/MS; the quantitation channels are marked with *.</p

Excretion profiles of four oxidative biomarkers after single-dose exposure to maleic acid in male rats.

<p>(a) 8-OHdG levels remain elevated and persist until day 5; (b) 8-NO₂Gua levels display similar trend to that of 8-OHdG; (c) 8-isoPFG_2α levels demonstrate elevation and persistence until day 6; (d) HNE-MA levels remain less affected after single-dose exposure to maleic acid. *, ** indicate statistically significant at <i>p</i><0.05 and 0.01, respectively. Dose groups receiving 0 mg/kg (●), 6 mg/kg (○),and 60 mg/kg (▼) are denoted accordingly.</p

(a) Specimen after lag screw excessive migration (≥10 mm); (b) TAD values of the Blade Screw and traditional DHS groups immediately after surgery and at 3-months follow-up.

<p>(a) Specimen after lag screw excessive migration (≥10 mm); (b) TAD values of the Blade Screw and traditional DHS groups immediately after surgery and at 3-months follow-up.</p

(a) Size of a test block; (b) Cellular rigid polyurethane foam (Type 1522–11) used to simulate a mild osteoporotic bone; (c) Open-cell rigid polyurethane foam (Type 1522–524) used to simulate a severely osteoporotic bone.

<p>(a) Size of a test block; (b) Cellular rigid polyurethane foam (Type 1522–11) used to simulate a mild osteoporotic bone; (c) Open-cell rigid polyurethane foam (Type 1522–524) used to simulate a severely osteoporotic bone.</p

Body weight change in maleic acid-treated SD rats.

<p>Body weight change in maleic acid-treated SD rats.</p

A femoral head test model was fixed in the HIPS system and subjected to multi-axial loading.

<p>A femoral head test model was fixed in the HIPS system and subjected to multi-axial loading.</p