Study of urinary 2-{[2-(acetylamino-2-carboxyethyl]sulfanyl}butanedioic acid, a mercapturic acid of rats treated with maleic acid

Luo, Yu‐Syuan; Tsai, Hsin-Yun; Chen, Hsin‐Chang; Wu, Chunchi; Shen, Li; Chung, Wen-Sheng; Chiang, Su‐Yin; Wu, Kaung-Hsiung

doi:10.1016/j.toxlet.2015.05.011

Cited by 4 publications

(3 citation statements)

References 25 publications

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“…3 However, MA is one modifier of starch that has not been approved for that purpose due to numerous past studies demonstrating that it causes kidney damage, including Fanconi syndrome, 4 type II renal tubular acidosis, 5 aminoaciduria, 6 and so on. 1,7 Nonetheless, in 2013, some Taiwanese food companies illegally added maleic anhydride to form a modified starch containing maleic acid, causing a toxic starch event that had a tremendous effect on the health of the affected individuals. 1 Starch is a homopolysaccharide composed of glucose units which are linked by glycosidic linkages and have many hydroxyl groups, 2 such that, when it is mixed with maleic anhydride, it reacts to form modified starch.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the price of industrial maleic anhydride is relatively low, which explains why some unscrupulous companies chose to use it illegally to process traditional snacks. 7 The kidneys function to remove waste from the blood, as well as to regulate the amount of water, osmotic pressure, electrolyte concentration, and hormone secretion in the body. The mechanism of tubular reabsorption mainly uses the sodium-potassium ATP pump to diffuse sodium-potassium ions and drive substances to diffuse into the cells.…”

Section: Introductionmentioning

confidence: 99%

“…27 At present, a wide range of past studies have already indicated that the consumption of maleic acid can cause kidney damage. 1,[3][4][5][6][7]14,16 However, most of those studies discussed the damage caused to renal tubules. As such, the effects of MA on the kidneys and related protein expression are still not clear enough.…”

Section: Introductionmentioning

confidence: 99%

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Proteomic analysis of rat kidney under maleic acid treatment by SWATH‐MS technology

Chien

Xue

Chen

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale Maleic acid is an industrial‐grade chemical that is often used in adhesives, stabilizers, and preservatives. It is unknown whether long‐term consumption of maleic acid modified starch is harmful to humans. However, many studies have indicated that maleic acid causes renal tubular damage in animal models, even as the associated pathways remain unclear. Sequential window acquisition of all theoretical fragment ion spectra (SWATH) is the most innovative of the label‐free quantitative technologies which have better quantification performance. Therefore, SWATH technology was used to investigate the effect of maleic acid on the rat kidney proteome in this study. Methods Sprague‐Dawley(SD) rats were treated with 0 mg/kg (control), 6 mg/kg (low‐dose), 10 mg/kg (medium‐dose), and 60 mg/kg (high‐dose) of maleic acid. After kidney protein extraction, 28% SDS‐PAGE was used, followed by in‐gel digestion and desalting. Next, the samples were analyzed with ultra‐performance liquid chromatography (UPLC) coupled with quadrupole time‐of‐flight mass spectrometry (Q‐TOF MS), and data‐dependent acquisition (DDA) and SWATH technology were also used. The gene ontology and pathway analysis were accomplished. Ultimately, these protein biomarkers were validated by using scheduled high‐resolution multiple reaction monitoring (sMRMHR). Results Comparisons of the control group with the other three groups revealed that 95, 130, and 103 proteins were expressed at significantly different levels in the control group and in the low‐dose, medium‐dose, and high‐dose groups, respectively. According to the gene ontology analysis, the major processes that these proteins were involved in were metabolic processes, biological regulation, cellular processes, and responses to stimuli; the major functions that these proteins were involved in were binding, hydrolase activity, catalytic activity, and oxidoreductase activity; and the major cellular components hat they were involved in were the cytoplasm, extracellular region, membrane, and mitochondria. According to the KEGG pathway analysis, these proteins were involved in 35 pathways, five of which, the carbohydrate metabolism, folate biosynthesis, renal tubular resorption, amino acid metabolism, and Ras signaling pathways, are discussed in this study. Ultimately, 19 proteins involved in 12 important pathways were validated by sMRMHR. Conclusions It was demonstrated that maleic acid caused insufficient energy production, which might lead to a decrease in the activity of the sodium‐potassium ATP pump and hydrogen ion ATP pump, which could in turn have caused renal tubular resorption and hydrogen ion regulation to be blocked, thus leading to the accumulation of hydrogen ions in the renal tubules, which would then result in renal tubular acidification followed finally by Fanconi syndrome.

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