Mengmeng Huang

Unravelling effects of flavanols and their derivatives on acrylamide formation via support vector machine modelling

This study investigated the effect of flavanols and their derivatives on acrylamide formation under low-moisture conditions via prediction using the support vector regression (SVR) approach. Acrylamide was generated in a potato-based equimolar asparagine-reducing sugar model system through oven heating. Both positive and negative effects were observed when the flavonoid treatment ranged 1-10,000μmol/L. Flavanols and derivatives (100μmol/L) suppress the acrylamide formation within a range of 59.9-78.2%, while their maximal promotion effects ranged from 2.15-fold to 2.84-fold for the control at a concentration of 10,000μmol/L. The correlations between inhibition rates and changes in Trolox-equivalent antioxidant capacity (ΔTEAC) (RTEAC-DPPH=0.878, RTEAC-ABTS=0.882, RTEAC-FRAP=0.871) were better than promotion rates (RTEAC-DPPH=0.815, RTEAC-ABTS=0.749, RTEAC-FRAP=0.841). Using ΔTEAC as variables, an optimized SVR model could robustly serve as a new predictive tool for estimating the effect (R: 0.783-0.880), the fitting performance of which was slightly better than that of multiple linear regression model (R: 0.754-0.880).

Characterization of acrylamide-induced oxidative stress and cardiovascular toxicity in zebrafish embryos

Acrylamide (AA) is a high production volume chemical in industrial applications and widely found in baked or fried carbohydrate-rich foods. In this study, we unravelled that AA induced developmental toxicity associated with oxidative stress status and disordered lipid distribution in heart region of developing zebrafish. Treatment with AA caused a deficient cardiovascular system with significant heart malformation and dysfunction. We also found that AA could reduce the number of cardiomyocytes through the reduced capacity of cardiomyocyte proliferation rather than cell apoptosis. The cardiac looping and ballooning appeared abnormal though cardiac chamber-specific identity in the differentiated myocardium was maintained well after AA treatment through MF20/S46 immunofluorescence assay. Furthermore, treatment with AA disturbed the differentiation of atrioventricular canal, which was demonstrated by the disordered expressions of the atrioventricular boundary markers bmp4, tbx2b and notch1b and further confirmed by the ectopic expressions of the cardiac valve precursor markers has2, klf2a and nfatc1 through whole-mount in situ hybridization. Thus, our studies provide the evidence of cardiac developmental toxicity of AA in the cardiovascular system, and also raised health concern about the harm of trans-placental exposure to high level of AA for foetuses and the risk of high exposure to AA for the pregnant women.

Exposure to acrylamide induces cardiac developmental toxicity in zebrafish during cardiogenesis

Acrylamide (AA), an environmental pollutant, has been linked to neurotoxicity, genotoxicity and carcinogenicity. AA is widely used to synthesize polymers for industrial applications, is widely found in Western-style carbohydrate-rich foods and cigarette smoke, and can also be detected in human umbilical cord blood and breast milk. This is the first study that demonstrated the cardiac developmental toxicity of AA in zebrafish embryos. Post-fertilization exposure to AA caused a clearly deficient cardiovascular system with a shrunken heart and abortive morphogenesis and function. Disordered expression of the cardiac genes, myl7, vmhc, myh6, bmp4, tbx2b and notch1b, as well as reduced number of myocardial cells and endocardial cells, indicated the collapsed development of ventricle and atrium and failed differentiation of atrioventricular canal (AVC). Although cell apoptosis was not affected, the capacity of cardiomyocyte proliferation was significantly reduced by AA exposure after fertilization. Further investigation showed that treatment with AA specifically reduced the expressions of nkx2.5, myl7 and vmhc in the anterior lateral plate mesoderm (ALPM) during the early cardiogenesis. In addition, AA exposure disturbed the restricted expressions of bmp4, tbx2b and notch1b during atrioventricular (AV) valve development and cardiac chambers maturation. Our results showed that AA-induced cardiotoxicity was related to decreased cardiac progenitor genes expression, reduced myocardium growth, abnormal cardiac chambers morphogenesis and disordered AVC differentiation. Our study demonstrates that AA exposure during a time point analogous to the first trimester in humans has a detrimental effect on early heart development in zebrafish. A high ingestion rate of AA-containing products may be an underlying risk factor for cardiogenesis in fetuses.

Serum polyfluoroalkyl chemicals are associated with risk of cardiovascular diseases in national US population

BACKGROUND Perfluoroalkyl chemicals (PFCs) as possible cardiovascular disrupters are universally detected in humans. However, evidence from epidemiological studies appears insufficient and ambiguous. OBJECTIVES We aim to examine the serum PFCs levels and their associations with the prevalence of cardiovascular diseases (CVD) and related outcomes in general US population. METHODS We investigated the serum levels of 12 major PFCs, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EPAH), 2-(N-methyl-perfluorooctane sulfonamido) acetate (MPAH), perfluorodecanoic acid (PFDE), perfluorobutane sulfonate (PFBS), perfluoroheptanoic acid (PFHP), perfluorononanoic acid (PFNA), perfluorooctane sulfonamide (PFSA), perfluoroundecanoic acid (PFUA), and perfluorododecanoic acid (PFDO), in 10,859 participants from the National Health and Nutritional Examination Survey (NHANES) 1999-2014. Logistic regression models were used to estimate the associations between serum PFCs and 5 self-reported CVD outcomes, including congestive heart failure, coronary heart disease, angina pectoris, heart attack, and stroke. Linear regression analyses were used to estimate the PFCs and their associations with 8 traditional CVD risk factors like serum triglyceride and total cholesterol. RESULTS In multivariable-adjusted models, total PFCs were positively associated with total CVD (p for trend = 0.0166), independent of traditional CVD risk factors, such as smoking status, diabetes, hypertension and serum cholesterol level. Compared with reference quartile of total PFCs levels, the multivariable adjusted odds ratios in increasing quartiles were 1.23 [95% confidence interval (CI): 0.91-1.66], 1.47 (95% CI: 1.14-1.89) and 1.45 (95% CI: 1.06-1.98) for total CVD. Similar positive associations were found if considering individual PFCs including PFOS, PFUA, MPAH, EPAH, PFDO, PFSA and PFBS. In addition, serum levels of MPAH and PFDO were positively associated with congestive heart failure; PFNA, PFDE, and PFUA were positively associated with coronary heart disease; PFUA and PFDO were positively associated with angina pectoris; and PFNA was positively associated with heart attack. CONCLUSIONS Our findings suggested that exposure to PFCs was positively associated with risk of CVD. Further longitudinal studies are needed to increase our understanding about the role of PFCs exposure in the prevalence of CVD.

Unravelling the effect of flavonoids on the kinetic profiles of acrylamide in the Maillard reaction

Acrylamide is mainly generated from asparagine and reducing sugars. The comprehensive kinetic profile of acrylamide and Maillard reaction products (MRP) is important for understanding the control of acrylamide. We unraveled the role of flavonoids in the kinetic process of acrylamide via a potato-based asparagine–glucose microwave heating system. Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was employed for the simultaneous determination of asparagine, glucose, fructose and acrylamide. The multi-response non-linear regression models were used for kinetic parameter estimation. The results indicated a positive role of flavonoids in the fructose-participating (k3: 0.461–0.674; P 0.05). The addition of flavonoids significantly reduces the formation of acrylamide during the advanced stage (k4: 2.311–4.327; P 0.05). Treatment of flavonoids has no significant impact on the formation of melanoidins (k5: 3.645–4.368; P > 0.05) and retains the original sensory attributes of MRP. These findings favor thinking mitigation strategies via the use of additives during food processing.

Association of acrylamide hemoglobin biomarkers with obesity, abdominal obesity and overweight in general US population: NHANES 2003–2006

Exposure to chemical contaminants is considered as one of risk factors to the current epidemic of obesity. Acrylamide (AA) is a ubiquitous chemical contaminant in environmental waste, mainstream cigarette smoke and carbohydrate-rich foods, and widely used in industrial manufacturers and cosmetics. Few studies have highlighted the association of daily exposure to AA with obesity-related outcomes. We analyzed data from 8364 participants who aged 20-85years and were recruited in National Health and Nutrition Examination Surveys (NHANES) 2003-2006. We established the model of PROC Survey Logistic regressions via using AA biomarkers in blood, hemoglobin adducts of acrylamide and glycidamide (HbAA and HbGA), as the measure of internal exposure to AA, and assessing obesity, abdominal obesity and overweight with body mass index (BMI) or waist circumference (WC). After the adjustment of sociodemographic variables, lifestyle behaviors, and health-related factors, the ratio of HbGA to HbAA (HbGA/HbAA) was significantly associated with obesity (p for trend<0.0001). The odd ratios (ORs) with 95% confidence intervals (CIs) of HbGA/HbAA across increasing quartiles were 1.740 (1.413-2.144), 2.604 (2.157-3.144), and 2.863 (2.425-3.380) compared with the lowest quartile. HbGA was positively associated with obesity [OR (95% CI): 1.226 (1.041-1.443), 1.283 (1.121-1.468), and 1.398 (1.165-1.679); p for trend=0.0004], while HbAA was inversely associated with obesity [OR (95% CI): 0.839 (0.718-0.980), 0.713 (0.600-0.848), and 0.671 (0.554-0.811); p for trend<0.0001]. Negative associations were found between the sum of HbAA and HbGA (HbAA+HbGA) and the body weight outcomes. Similar associations were also observed between the hemoglobin biomarkers of AA and abdominal obesity as well as overweight. Thus, the hemoglobin adducts of AA as long-term internal exposure biomarkers are strongly associated with obesity-related outcomes in a population of US adults.

Exposure to acrylamide and the risk of cardiovascular diseases in the National Health and Nutrition Examination Survey 2003–2006

BACKGROUND Long-term exposure to acrylamide (AA) from diet sources may induce oxidative stress and chronic inflammation. However, the association between AA exposure and the prevalence of cardiovascular diseases (CVD) remains unclear. OBJECTIVES We aimed to examine the association between blood exposure levels of AA biomarkers and the prevalence of main types of CVD in a general population of US adults. METHODS We analyzed the associations between AA hemoglobin biomarkers [hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA), sum of HbAA and HbGA (HbAA+HbGA), and ratio of HbGA to HbAA (HbGA:HbAA)] and self-reported diagnosis of CVD in 8290 adults (≥20 years of age) from the National Health and Nutrition Examination Survey (NHANES) 2003-2006. Multivariable logistic regression models were employed for estimating the associations in three groups classified by the combination of smoking status and serum cotinine levels. RESULTS In people exposed to environmental tobacco smoke (n = 4670), HbGA, HbAA+HbGA, and HbGA:HbAA were significantly and inversely associated with the prevalence of total CVD (p < 0.0001, p = 0.0155, and p = 0.0014 for trend, respectively) after adjusting for various covariates. The odd ratios (ORs) for total CVD in the highest quartiles of HbGA, HbAA+HbGA, and HbGA:HbAA were 0.311 [95% confidence interval (CI): 0.193-0.500], 0.664 (95% CI: 0.485-0.911), and 0.495 (95% CI: 0.326-0.752) when compared with the individual lowest quartiles. In active smokers (n = 2432), HbAA was positively associated with CVD risk (p = 0.0088 for trend), while HbGA:HbAA was inversely related to total CVD (p = 0.0137 for trend). However, no significant associations of any AA hemoglobin biomarker with total and individual CVD prevalence were observed in the nonsmoking group (n = 1188). CONCLUSIONS AA hemoglobin biomarkers are significantly associated with CVD in the active smoking group and the group exposed to environmental tobacco smoke but not in the nonsmoking group. Further prospective studies should clarify the causal relationship between HbAA and HbGA and the prevalence of CVD.

Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation

We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1–10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633–0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926–0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation.