Inhibition of polyphenols on Maillard reaction products and their induction of related diseases: A comprehensive review.

BACKGROUND: Food products undergo a pronounced Maillard reaction (MR) during the cooking process, leading to the generation of substantial quantities of Maillard reaction products (MRPs). Within this category, advanced glycation end products (AGEs), acrylamide (AA), and heterocyclic amines (HAs) have been implicated as potential risk factors associated with the development of diseases. PURPOSE: To explore the effects of polyphenols, a class of bioactive compounds found in plants, on the inhibition of MRPs and related diseases. Previous research has mainly focused on their interactions with proteins and their effects on the gastrointestinal tract and other diseases, while fewer studies have examined their inhibitory effects on MRPs. The aim is to offer a scientific reference for future research investigating the inhibitory role of polyphenols in the MR. METHODS: The databases PubMed, Embase, Web of Science and The Cochrane Library were searched for appropriate research. RESULTS: Polyphenols have the potential to inhibit the formation of harmful MRPs and prevent related diseases. The inhibition of MRPs by polyphenols primarily occurs through the following mechanisms: trapping α-dicarbonyl compounds, scavenging free radicals, chelating metal ions, and preserving protein structure. Simultaneously, polyphenols exhibit the ability to impede the onset and progression of related diseases such as diabetes, atherosclerosis, cancer, and Alzheimer's disease through diverse pathways. CONCLUSION: This review presents that inhibition of polyphenols on Maillard reaction products and their induction of related diseases. Further research is imperative to enhance our comprehension of additional pathways affected by polyphenols and to fully uncover their potential application value in inhibiting MRPs.

Identification of potato varieties suitable for cold storage and reconditioning: A safer alternative to anti-sprouting chemicals for potato sprouting control.

Low temperature storage as an alternative to anti-sprouting chemicals in potato storage may induce reducing sugars (RS) accumulation (i.e. glucose and fructose) in potato tubers. This phenomenon is called "cold induced sweetening" (CIS) and occurs in certain varieties. CIS leads to a decrease in the organoleptic qualities and darkening of processed potato and the accumulation of toxic molecules such as acrylamide. To identify potato varieties suitable for storage at low temperatures, we screened six commercial processing varieties: Lady Claire (LC), Verdi, Kiebitz (KB), Pirol, Agria and Markies for their CIS characteristics and sprout-forming potential after storage at 4 °C and 8 °C. Our findings reveal that 4 °C storage allows for efficient sprout reduction in all six tested varieties for up to 4.5 months of storage. Three CIS-resistant varieties, namely Verdi, Lady Claire and Kiebitz, were identified as able to be stored for up to four months at 4 °C with limited increase in glucose content. Conversely, Pirol, Agria and Markies showed an increase in glucose content with a decrease in storage temperature and can be considered as CIS-susceptible varieties. After processing into crisps, the CIS-susceptible varieties displayed poor crisp color quality (brown to black color crisps) after storage for two months at 4 °C compared to the storage at 8 °C, whereas the CIS-resistant varieties had good crisp color quality (pale yellow color crisps) after storage at both 4 and 8 °C. Interestingly, the trends of total RS and/or glucose content in the CIS-resistant and in the CIS-susceptible varieties were correlated with the trends in Vacuolar Invertase (VInv) gene expression for most varieties, as well as with the trends in acrylamide content after processing. In addition, reconditioning of Markies variety after storage at 4 °C by gradually increasing the temperature to 15 °C resulted in a significant decrease of VInv transcript levels (reduction of 80 %), acrylamide content (reduction of 75 %) and glucose content when compared to a storage at 4 °C without reconditioning. Those results demonstrate that the reconditioning technique is a key factor for a sustainable potato storage and for improving the quality of processed potatoes.

An exploratory study to assess the knowledge, attitudes and practices of Lebanese residents towards acrylamide.

INTRODUCTION: For years, heat treatment has been an essential method for ensuring mature food that meet the desired quality and safety characteristics. However, this process could lead to the formation of harmful compounds such as acrylamide. In this study we aimed to investigate the knowledge, attitudes and practices (KAPs) of the Lebanese population toward the potential risk associated with acrylamide. MATERIALS & METHODS: An online survey (n = 598) was conducted among residents in Lebanon aged 18 years and above. The survey was divided into five sections including participants' sociodemographic characteristics, knowledge, attitude and practice sections, and some questions related to consumer's preferences. RESULTS & DISCUSSION: The results showed that the majority of the participants had low food safety knowledge regarding acrylamide. Specifically, 82.9% of the consumers had no idea about the chemical, its formation, the foods with a high risk of acrylamide formation and the health risks associated with its exposure. Despite lack of knowledge, good domestic food practices (storage, pre-treatment) were noticed among participants. Moreover, the majority of consumers (> 80%) showed positive attitude towards proper acrylamide labeling. Participants with a bachelor's degree appeared to have a more positive attitude toward food safety compared to those with no qualifications (p<0.001). CONCLUSION: Despite the high consumption of acrylamide by the consumers in Lebanon through fried potatoes, bread, and coffee, the majority have no idea about acrylamide's presence in food, its sources and its adverse health effects. Raising awareness among the public, involving policy makers in addressing the issue of clear labeling and encouraging the adoption of alternative practices to reduce acrylamide are all crucial to protect consumers' health in Lebanon and promote healthier food consumption habits.

Rosmarinic acid mitigates acrylamide induced neurotoxicity via suppressing endoplasmic reticulum stress and inflammation in mouse hippocampus.

BACKGROUND: Acrylamide (ACR) is a widely used compound that is known to be neurotoxic to both experimental animals and humans, causing nerve damage. The widespread presence of ACR in the environment and food means that the toxic risk to human health can no longer be ignored. Rosmarinic acid (RA), a natural polyphenolic compound extracted from the perilla plant, exhibits anti-inflammatory, antioxidant, and other properties. It has also been demon strated to possess promising potential in neuroprotection. However, its role and potential mechanism in treating ACR induced neurotoxicity are still elusive. PURPOSE: This study explores whether RA can improve ACR induced neurotoxicity and its possible mechanism. METHODS: The behavioral method was used to study RA effect on ACR exposed mice's neurological function. We studied its potential mechanism through metabolomics, Nissl staining, HE staining, immunohistochemical analysis, and Western blot. RESULTS: RA pretreatment reversed the increase in mouse landing foot splay and decrease in spontaneous activity caused by 3 weeks of exposure to 50 mg/kg/d ACR. Further experiments demonstrated that RA could prevent ACR induced neuronal apoptosis, significantly downregulate nuclear factor-κB and tumor necrosis factor-α expression, and inhibit NOD-like receptor protein 3 inflammasome activation, thereby reducing inflammation as confirmed by metabolomics results. Additionally, RA treatment prevented endoplasmic reticulum stress (ERS) caused by ACR exposure, as evidenced by the reversal of significant P-IRE1α,TRAF2,CHOP expression increase. CONCLUSION: RA alleviates ACR induced neurotoxicity by inhibiting ERS and inflammation. These results provide a deeper understanding of the mechanism of ACR induced neurotoxicity and propose a potential new treatment method.

A green-footprint approach for parallel multiclass analysis of contaminants in roasted coffee via LC-HRMS.

The development and validation of a simple, comprehensive, and environment-friendly procedure to determine pesticide residues, naturally occurring and processing contaminants in roasted coffee is presented. A solid-liquid extraction of pesticides and mycotoxins with ethyl acetate and the concurrent partition of acrylamide to an aqueous phase follows a parallel analytical strategy that requires a single analytical portion to determine contaminants that are typically analyzed by dedicated single residue methods. The partition rules the lipids out of the aqueous extract before an "in-tube" dispersive solid phase microextraction (dSPME) for acrylamide retention. This is followed by the elution with buffer prior to injection. This extract is independently introduced into the system front end followed by the injection of the compounds from the organic phase, yet all spotted in the same run. A novel liquid chromatography high-resolution mass spectrometry (LC-HRMS) method setup enables the quantification of 186 compounds at 10 µg/kg, 226 at 5 µg/kg, and the acrylamide at 200 µg/kg for a total of 414 molecules, with acceptable recoveries (70-120%) and precision (RSD < 20%) making this strategy significantly faster and cost-effective than the dedicated single residue methods. Even though the presence of chlorpyrifos, acrylamide, and ochratoxin A was confirmed on samples of different origins, the findings were below the limit of quantification. During the storage of raw coffee, no proof of masking of OTA was found; however, condensation with glucose was evidenced during thermal processing experiments with sucrose by using stable isotope labeling (SIL). No detected conjugates were found in roasted nor in commercial sugar-added torrefacto samples, an industrial processing usually carried out above the decomposition temperature of the disaccharide.

Food emulsifiers increase toxicity of food contaminants in three human GI tract cell lines.

Food products simultaneously containing both food contaminants and emulsifiers are common in baked products, coffee and chocolate. Little is known regarding how food contaminants and emulsifiers interact and alter toxicity. Recent studies have shown that while emulsifiers themselves have little toxicity, they could cause changes in the gut microenvironment and lead to issues such as increased uptake of allergens. This study examined toxic effect of two common process contaminants acrylamide (AA) and benzo [a]pyrene (BAP) combined with food emulsifiers polyoxyethylene sorbitan monooleate (TW) or glycerol monostearate (G). In liver cell line HepG2 and gastrointestinal cell lines HIEC6 and Caco-2, toxicities of AA and BAP were increased by TW but not by G as indicated by decrease in IC50 values. Addition of TW also exacerbated gene expression changes caused by AA or BAP. Cellular uptake and cell membrane permeability were enhanced by TW but not by G, but tight junction proteins of Caco-2 monolayer was impacted by both emulsifiers. These results suggested that TW could increase toxicity of AA and BAP through increasing cell permeability thus chemical uptake and potentially through other interactions. The study is to draw the attention of regulators on the potential synergistic interaction of co-occurring chemicals in food.

Identifying high-risk factors and mitigation strategies for acrylamide formation in air-fried lotus root chips: Impact of cooking parameters, including temperature, time, presoaking, and seasoning.

This study was conducted to identify high-risk factors and mitigation strategies for acrylamide formation in air-fried lotus root chips by studying the impact of various cooking parameters, including temperature, time, presoaking, and pre-seasoning treatments. The temperature and time had a surprisingly high impact on acrylamide formation. The chips prepared at high temperatures with longer cooking times contained an extremely high acrylamide content, reaching 12,786 ng/g (e.g., 170°C/19 min). A particularly concerning discovery was that the chips with extremely high acrylamide content (up to 17 times higher than the EU benchmark level for potato chips) did not appear overcooked or taste burnt. Higher cooking temperatures required shorter cooking times to properly cook lotus root chips for consumption. A high temperature with a short cooking time (170°C/13 min) greatly benefited acrylamide reduction compared to low temperature with a long cooking time (150°C/19 min). Presoaking in a 0.1% acetic acid solution and pre-seasoning with 1% salt reduced acrylamide levels by 61% and 47%, respectively. However, presoaking in water, vinegar solution, and citric acid solution did not significantly decrease the acrylamide content in the chips. Furthermore, some seasonings significantly increased acrylamide levels (up to 7.4 times higher). For the first time, these findings underscore the high risks associated with air-frying lotus root chips without considering these factors. This study also provides proper air-frying parameters and pretreatment strategies for minimizing acrylamide formation in air-fried lotus chips.

Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling.

This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The study evaluated alterations in relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy and phospholipids content, oxidative and nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target of rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood-testis barrier (BTB) remodeling markers, testicular autophagy and apoptotic markers, as well as histopathological alterations in testicular tissues. The results revealed that eugenol treatment demonstrated a significant improvement in sperm quality parameters, with increased sperm cell concentration, progressive motility live sperm, and a reduction in abnormal sperm, compared to the ACR-intoxicated group. Furthermore, eugenol administration increased the levels of seminal plasma amino acids in a dose-dependent manner. In addition, eugenol treatment dose-dependently improved testicular oxidative/nitrosative stress biomarkers by increasing oxidized and reduced glutathione levels and reducing malondialdehyde and nitric oxide contents as compared to ACRgroup. However, eugenol treatment at a high dose restored the expression of AMPK, PI3K, and mTOR genes, to levels comparable to the control group, while significantly increasing p-AKT content compared to the ACRgroup. In conclusion, the obtained findings suggest the potential of eugenol as a therapeutic agent in mitigating ACR-induced detrimental effects on the male reproductive system via amelioration of ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR signaling pathways and BTB remodeling.

Evaluation of physiochemical and biomedical properties of psyllium-poly(vinyl phosphonic acid-co-acrylamide)-cl-N,N-methylene bis acrylamide based hydrogels.

Present investigation deals with the synthesis of psyllium based copolymeric hydrogels and evaluation of their physiochemical and biomedical properties. These copolymers have been prepared by grafting of poly(vinyl phosphonic acid) (poly (VPA)) and poly(acrylamide) (poly(AAm)) onto psyllium in the presence of crosslinker N,N-methylene bis acrylamide (NNMBA). These copolymers [psyllium-poly(VPA-co-AAm)-cl-NNMBA] were characterized by field emission-scanning electron micrographs (FE-SEM), electron dispersion X-ray analysis (EDAX), Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), 13C-nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA)- differential thermal analysis (DTG). FESEM, AFM and XRD demonstrated heterogeneous morphology with a rough surface and an amorphous nature. Diffusion of ornidazole occurred with a non-Fickian diffusion mechanism, and the release profile data was fitted in the Korsemeyer-Peppas kinetic model. Biochemical analysis of hydrogel properties confirmed the blood-compatible nature during blood-polymer interactions and revealed haemolysis value 3.95 ± 0.05 %. The hydrogels exhibited mucoadhesive character during biomembrane-polymer interactions and demonstrated detachment force = 99.0 ± 0.016 mN. During 2,2-diphenyl-1-picrylhydrazyl reagent (DPPH) assay, free radical scavenging was observed 37.83 ± 3.64 % which illustrated antioxidant properties of hydrogels. Physiological and biomedical properties revealed that these hydrogels could be explored for drug delivery uses.

Selenium reduces acrylamide-induced testicular toxicity in rats by regulating HSD17B1, StAR, and CYP17A1 expression, oxidative stress, inflammation, apoptosis, autophagy, and DNA damage.

This study investigated the effects of Selenium (Se) on testis toxicity induced by Acrylamide (ACR) in rats. In our study, 50 male adult rats were used, and the rats were divided into five groups; control, ACR, Se0.5 + ACR, Se1 + ACR, and Se1. Se and ACR treatments were applied for 10 days. On the 11th day of the experimental study, intracardiac blood samples from the rats were taken under anesthesia and euthanized. Sperm motility and morphology were evaluated. Dihydrotestosterone, FSH, and LH levels in sera were analyzed with commercial ELISA kits. MDA, GSH, TNF-α, IL-6, and IL-1ß levels and SOD, GPx, and CAT, activities were measured to detect the level of oxidative stress and inflammation in rat testis tissues. Expression analysis of HSD17B1, StAR, CYP17A1, MAPk14, and P-53 as target mRNA levels were performed with Real Time-PCR System technology for each cDNA sample synthesized from rat testis RNA. Testicular tissues were evaluated by histopathological, immunohistochemical, and immunofluorescent examinations. Serum dihydrotestosterone and FSH levels decreased significantly in the ACR group compared to the control group, while LH levels increased and a high dose of Se prevented these changes caused by ACR. A high dose of Se prevented these changes caused by ACR. ACR-induced testicular oxidative stress, inflammation, apoptosis, changes in the expression of reproductive enzymes, some changes in sperm motility and morphology, DNA, and tissue damage, and Se administration prevented these pathologies caused by ACR. As a result of this study, it was determined that Se prevents oxidative stress, inflammation, apoptosis, autophagy, and DNA damage in testicular toxicity induced by ACR in rats.

Acrylamide in potato chips in Iran, health risk assessment and mitigation.

This study aimed to determine the acrylamide content in potato chips sold in Kermanshah, Iran and assess the potential health concerns associated with acrylamide exposure. HPLC-DAD was used to analyse 120 samples across 40 brands. The possible non-carcinogenic risk index for adults was below 1 for all 40 brands (100%), but for children it was only below 1 for 9 brands (22.5%) and above 1 for 31 brands (77.5%). Regarding the possible carcinogenic risk index, for adults only 1 out of 40 brands rated > 10-4, whereas for children all brands rated > 10-4. This shows that children's exposure to acrylamide through potato chips consumption in Kermanshah can be considered a risk on cancer and exposure of adults requires attention and monitoring. The best way to reduce acrylamide in potato chips and associated health risks is to improve the production process, especially temperature and time.

The effects of pinealectomy and melatonin treatment in acrylamide-induced nephrotoxicity in rats: Antioxidant and anti-inflammatory mechanisms.

OBJECTIVE: Acrylamide (AA) is toxic and forms in food that undergoes high-temperature processing. This study aimed to investigate the effects of AA-induced toxicity on renal tissue in pinealectomized rats and the possible protective effect of exogenous Melatonin (ML) administration. MATERIALS AND METHODS: Sixty rats were randomized into 6 groups (n = 10): Sham, Sham+AA, Sham+AA+ML, PX, PX+AA, and PX+AA+ML. Sham and pinealectomized rats received AA (25 mg/kg/day orally) and ML (0.5 ml volume at 10 mg/kg/day, intraperitoneal) for 21 days. RESULTS: The results showed that malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), tumor necrosis factor-α (TNF-α), and interleukin 1ß (IL-1ß) levels of the kidney and urea and creatinine levels of serum in the PX (pinealectomy)+AA group were more increased than in the Sham+AA group. In addition, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) levels decreased more in the PX+AA group than in the Sham+AA group. Also, we observed more histopathologic damage in the PX+AA group. On the other hand, up-regulation of kidney tissue antioxidants, down-regulation of tissue oxidants, and improvement in kidney function were achieved with ML treatment. Also, histopathological findings such as inflammatory cell infiltration, shrinkage of glomeruli, and dilatation of tubules caused by AA toxicity improved with ML treatment. CONCLUSION: ML supplementation exhibited adequate nephroprotective effects against the nephrotoxicity of AA on pinealectomized rat kidney tissue function by balancing the oxidant/antioxidant status and suppressing the release of proinflammatory cytokines.

Reconstructing hepatic metabolic profile and glutathione-mediated metabolic fate of acrylamide.

The toxicity of acrylamide (AA) has continuously attracted wide concerns as its extensive presence from both environmental and dietary sources. However, its hepatic metabolic transformation and metabolic fate still remain unclear. This study aims to unravel the metabolic profile and glutathione (GSH) mediated metabolic fate of AA in liver of rats under the dose-dependent exposure. We found that exposure to AA dose-dependently alters the binding of AA and GSH and the generation of mercapturic acid adducts, while liver as a target tissue bears the metabolic transformation of AA via regulating GSH synthesis and consumption pathways, in which glutamine synthase (GSS), cytochrome P450 2E1 (CYP2E1), and glutathione S-transferase P1 (GSTP1) play a key role. In response to high- and low-dose exposures to AA, there were significant differences in liver of rats, including the changes in GSH and cysteine (CYS) activities and the conversion ratio of AA to glycidamide (GA), and liver can affect the transformation of AA by regulating the GSH-mediated metabolic pathway. Low-dose exposure to AA activates GSH synthesis pathway in liver and upregulates GSS activity and CYS content with no change in γ-glutamyl transpeptidase 1 (GGT1) activity. High-dose exposure to AA activates the detoxification pathway of GSH and increases GSH consumption by upregulating GSTP1 activity. In addition, molecular docking results showed that most of the metabolic molecules transformed by AA and GA other than themselves can closely bind to GSTP1, GSS, GGT1, N-acetyltransferase 8, and dimethyl sulfide dehydrogenase 1. The binding of AA-GSH and GA-GSH to GSTP1 and CYP2E1 enzymes determine the tendentiousness between toxicity and detoxification of AA, which exerts a prospective avenue for targeting protective role of hepatic enzymes against in vivo toxicity of AA.

Effect of elaboration process, crop year and irrigation on acrylamide levels of potential table olive varieties.

BACKGROUND: Table olives are widely consumed in the Mediterranean diet, and several typical Spanish and Portuguese varieties could potentially be used as such. In order to ensure a good-quality product, the effect of different factors such as elaboration processes, irrigation conditions, crop year and their crossover interaction on acrylamide content and antioxidant compounds needs to be deeply studied. RESULTS: When looking through irrigation, regulated deficit irrigation (RDI) presented lower acrylamide levels than rainfed conditions for 'Cordovil de Elvas', 'Picual' and 'Verdeal Alentejana'. No significant interactions were found between the type of irrigation and elaboration style for 'Arbequina' and 'Koroneiki' varieties. Although RDI had the largest concentration of total phenols, antioxidant activity was also the highest. The table olives harvested in the crop year of 2019 showed lower levels of acrylamide due to a significant relationship between the crop year and irrigation conditions. CONCLUSIONS: Novel varieties to be marketed should be taken into consideration for table olive elaboration. The impact of the crop year on the bioactive value of table olives and crossover interactions relies strongly in climatological conditions. Last but not least, the benefit of selecting the best irrigation and elaboration methods is crucial to ensure desirable acrylamide levels. © 2023 Society of Chemical Industry.

Covalent Inhibition by a Natural Product-Inspired Latent Electrophile.

Strategies to target specific protein cysteines are critical to covalent probe and drug discovery. 3-Bromo-4,5-dihydroisoxazole (BDHI) is a natural product-inspired, synthetically accessible electrophilic moiety that has previously been shown to react with nucleophilic cysteines in the active site of purified enzymes. Here, we define the global cysteine reactivity and selectivity of a set of BDHI-functionalized chemical fragments using competitive chemoproteomic profiling methods. Our study demonstrates that BDHIs capably engage reactive cysteine residues in the human proteome and the selectivity landscape of cysteines liganded by BDHI is distinct from that of haloacetamide electrophiles. Given its tempered reactivity, BDHIs showed restricted, selective engagement with proteins driven by interactions between a tunable binding element and the complementary protein sites. We validate that BDHI forms covalent conjugates with glutathione S-transferase Pi (GSTP1) and peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), emerging anticancer targets. BDHI electrophile was further exploited in Bruton's tyrosine kinase (BTK) inhibitor design using a single-step late-stage installation of the warhead onto acrylamide-containing compounds. Together, this study expands the spectrum of optimizable chemical tools for covalent ligand discovery and highlights the utility of 3-bromo-4,5-dihydroisoxazole as a cysteine-reactive electrophile.

Toxicity, formation, contamination, determination and mitigation of acrylamide in thermally processed plant-based foods and herbal medicines: A review.

Thermal processing is one of the important techniques for most of the plant-based food and herb medicines before consumption and application in order to meet the specific requirement. The plant and herbs are rich in amino acids and reducing sugars, and thermal processing may lead to Maillard reaction, resulting as a high risk of acrylamide pollution. Acrylamide, an organic pollutant that can be absorbed by the body through the respiratory tract, digestive tract, skin and mucous membranes, has potential carcinogenicity, neurological, genetic, reproductive and developmental toxicity. Therefore, it is significant to conduct pollution determination and risk assessment for quality assurance and security of medication. This review demonstrates state-of-the-art research of acrylamide focusing on the toxicity, formation, contamination, determination, and mitigation in taking food and herb medicine, to provide reference for scientific processing and ensure the security of consumers.

Acrylamide induces the activation of BV2 microglial cells through TLR2/4-mediated LRRK2-NFATc2 signaling cascade.

Acrylamide (ACR), a potential neurotoxin, is generated from the Maillard reaction between reducing sugars and free amino acids during food processing. Our work focuses on clarifying the role of the leucine-rich repeat kinase 2 (LRRK2) and nuclear factor of activated T cells, cytoplasmic 2 (NFATc2) in the polarization of BV2 cells to the M1 proinflammatory type induced by ACR. Specifically, ACR promoted the phosphorylation of LRRK2 and NFATc2 in BV2 microglia. Furthermore, selectively phosphorylated LRRK2 by ACR induced nuclear translocation of NFATc2 to trigger a neuroinflammatory cascade. Knock-down of LRRK2 by silencing significantly diminished ACR-induced microglial neurotoxic effect with the decline of IL-1ß, IL-6, and iNOS levels and the decrease of NFATc2 expression in BV2 cells. After pretreated with Toll-Like Receptor 2 (TLR2) and TLR4 inhibitors separately, both the activation of LRRK2 and the release of pro-inflammatory factors were inhibited in BV2 cells. Gallic acid (GA) is ubiquitous in most parts of the medicinal plant. GA alleviated the increased CD11b expression, IL-6 and iNOS levels induced by ACR in BV2 microglia. In conclusion, this study shows that ACR leads to the cascade activation of LRRK2-NFATc2 mediated by TLR2 and TLR4 to induce microglial toxicity.

Therapeutic role of melatonin on acrylamide-induced hepatotoxicity in pinealectomized rats: Effects on oxidative stress, NF-κB signaling pathway, and hepatocellular proliferation.

Acrylamide (AA) is formed in some foods by the cooking process at high temperatures, and it could be a carcinogen in humans and rodents. The purpose of the current study was to reveal the possible protective effects of melatonin against AA-induced hepatic oxidative stress, hepatic inflammation, and hepatocellular proliferation in pinealectomized rats. Hence, the sham and pinealectomized rats were consecutively given AA alone (25 mg/kg) or with melatonin (10 mg/kg) for 21 days. Melatonin acts as an antioxidant, anti-inflammatory, and antiapoptotic agent and introduces as a therapeutic strategy for AA-induced hepatotoxicity. Melatonin supplementation reduced AA-caused liver damage by decreasing the serum AST, ALT, and ALP levels. Melatonin raised the activities of SOD and CAT and levels of GSH and suppressed hepatic inflammation (TNF-α) and hepatic oxidative stress in liver tissues. Moreover, histopathological alterations and the disturbances in immunohistochemical expression of NF-κB and Ki67 were improved after melatonin treatment in AA-induced hepatotoxicity. Overall, our results demonstrate that melatonin supplementation exhibits adequate hepatoprotective effects against hepatotoxicity of AA on pinealectomized rat liver architecture and the tissue function through the equilibration of oxidant/antioxidant status, the regulation of cell proliferation and the suppression of the release of proinflammatory cytokines.

Synthesis of acrylamide-g-melanin/itaconic acid-g-psyllium based nanocarrier for capecitabine delivery: In vivo and in vitro anticancer activity.

The present research aims to synthesize the capecitabine-loaded core-shell nanoparticles of acrylamide-grafted melanin and itaconic acid-grafted psyllium (Cap@AAM-g-ML/IA-g-Psy-NPs) to deliver the drug to the targeted colonic area, enhancing their anti-cancer activity. The drug release behavior of Cap@AAM-g-ML/IA-g-Psy-NPs was studied at several biological pH in which maximum drug release (95 %) was observed at pH 7.2. The drug release kinetic data was in accordance with the first-order (R2 = 0.9706) kinetic model. The cytotoxicity of Cap@AAM-g-ML/IA-g-Psy-NPs was investigated on HCT-15 cell line and Cap@AAM-g-ML/IA-g-Psy-NPs demonstrated outstanding toxicity towards HCT-15 cell line. In-vivo study on DMH-induced colon cancer rat model also exhibited that Cap@AAM-g-ML/IA-g-Psy-NPs enhanced anticancer activity against cancer cells as compared to capecitabine. Histology studies of heart, liver and kidney cells indicate that inflation due to cancer induction by DMH is significantly reduced when treated with Cap@AAM-g-ML/IA-g-Psy-NPs. Thus, the present study procures a worthwhile and nominal approach toward the synthesis of Cap@AAM-g-ML/IA-g-Psy-NPs for anticancer applications.

Acrylamide bioaccessibility in potato and veggie chips. Impact of in vitro colonic fermentation on the non-bioaccessible fraction.

Potato-based products contribute largely to the daily intake of acrylamide. In addition to potato crisps, the European Commission has included veggie crisps in the list of foods that should be monitored for their acrylamide content. In the present study, acrylamide content in potato and veggie chips (sweet potato, beetroot and carrot) and their bioaccessibility after in vitro digestion was assessed. The non-bioaccessible fraction was also submitted to in vitro fermentation under colonic conditions. Faecal samples from volunteers of three age groups (children, adolescents and adults) were used to evaluate the microbiota effect on the acrylamide availability. Sweet potato chips exhibited the highest acrylamide content (2342 µg/kg), followed by carrot (1279 µg/kg), beetroot (947 µg/kg) and potato chips (524 µg/kg). After in vitro digestion, acrylamide bioaccessibility was significantly lower in veggie chips (59.7-60.4 %) than in potato chips (71.7 %). Potato and sweet potato chips showed the significantly lowest acrylamide content in the non-bioaccessible fraction (22.8 and 24.1 %, respectively) as compared with beetroot chips (28.4 %). After the fermentation step, acrylamide percentage in the soluble fraction of veggie chips ranged from 43.03 to 71.89 %, the highest values being observed in sweet potato chips fermented with microbiota from children. This fact would involve that the acrylamide was released from the non-bioaccessible fractions by the microbiota. These findings point out that the levels of potentially absorbable acrylamide after the complete gastrointestinal process could be modulated by both the food matrix composition and the microbiota. These factors should be further considered for a more precise risk assessment of dietary acrylamide in humans.