Acrylamide-induced Oxidative Stress Research Articles

Obesity Induces DNA Damage in Mammary Epithelial Cells Exacerbated by Acrylamide Treatment through CYP2E1-Mediated Oxidative Stress.

Obesity and environmental toxins are risk factors for breast cancer; however, there is limited knowledge on how these risk factors interact to promote breast cancer. Acrylamide, a probable carcinogen and obesogen, is a by-product in foods prevalent in the obesity-inducing Western diet. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to the genotoxic epoxide, glycidamide, and is associated with an increased risk for breast cancer. To investigate how acrylamide and obesity interact to increase breast cancer risk, female mice were fed a low-fat (LFD) or high-fat diet (HFD) and control water or water supplemented with acrylamide at levels similar to the average daily exposure in humans. While HFD significantly enhanced weight gain in mice, the addition of acrylamide did not significantly alter body weights compared to respective controls. Mammary epithelial cells from obese, acrylamide-treated mice had increased DNA strand breaks and oxidative DNA damage compared to all other groups. In vitro, glycidamide-treated COMMA-D cells showed significantly increased DNA strand breaks, while acrylamide-treated cells demonstrated significantly higher levels of intracellular reactive oxygen species. The knockdown of CYP2E1 rescued the acrylamide-induced oxidative stress. These studies suggest that long-term acrylamide exposure through foods common in the Western diet may enhance DNA damage and the CYP2E1-induced generation of oxidative stress in mammary epithelial cells, potentially enhancing obesity-induced breast cancer risk.

Zinc ameliorates acrylamide-induced oxidative stress and apoptosis in testicular cells via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway

ABSTRACT Background: Acrylamide is a toxic substance formed in some foods that require high-temperature cooking processes and has been implicated as a gonadotoxic agent. Zinc, on the other hand, is a known antioxidant with fertility-enhancing properties. Hence, this study was designed to explore the possible ameliorative effect of zinc in acrylamide-induced gonadotoxicity. Methods: Twenty-four male Wistar rats were randomized into control, acrylamide (10 mg/kg of acrylamide), acrylamide + 1 mg/kg of zinc, and acrylamide + 3 mg/kg of zinc. The administration was via the oral route and lasted for 56 days. Results: Zinc treatment ameliorated acrylamide-impaired sperm quality, normal testicular histoarchitecture, and hormonal balance, which was accompanied by increased testicular malondialdehyde and interleukin-1β and decreased testicular superoxide dismutase (SOD) and catalase (CAT). Furthermore, zinc prevented acrylamide-induced downregulation of testicular nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and B-cell lymphoma 2 (BCl2) expression and upregulation of testicular nuclear factor kappa B (NF-κB) and bcl-2-like protein 4 (bax) expression. Conclusion: In conclusion, zinc may protect against acrylamide-induced testicular toxicity, mediated by its antioxidant, anti-inflammatory, and antiapoptotic effects.

Carica papaya Fruit Extract Protects the Cerebellum of Wistar Rats Against Acrylamide-Induced Oxidative Stress

Acrylamide is a water-soluble vinyl monomer produced industrially as an agent for the production of plastics and cosmetics, in waste water management as a flocculation agent, and naturally in fried, baked, and roasted foods, especially when heated beyond 120 °C. Acrylamide (AC) is associated with severe neurotoxic complications through the initiation of oxidative stress. Hence the use of Carica papaya (CP), a natural antioxidant, in protecting the cerebellum of Wistar rats against acrylamide-induced oxidative stress. Forty adult female Wistar rats (180-200 g) were divided into four groups (n=10): Control (1 mL distilled water), AC (25 mg/kg), CP (300 mg/kg), and CP+AC (300 mg/kg+25 mg/kg). All treatments were administered orally for 21 days. Thereafter, the rats were weighed, and neurobehavioural tests were done. The rats were sacrificed, while their cerebella were dissected out and preserved for oxidative stress, antioxidant markers, and histological and immunohistochemical studies. Data were analysed using analysis of variance at p<0.05. There was decreased body weight, locomotor activities, and forelimb grip strength in the AC-treated group compared with the control and other treated groups. Increased lipid peroxidation and nitric oxide levels, decreased glutathione (GSH) levels, and catalase, superoxide dismutase, and glutathione peroxidase activities in the AC-treated groups compared with the control and other treated groups. Histologically, degeneration, pyknosis, shrinking and loss of Purkinje neurons, reactive astrogliosis, and apoptosis occurred in the AC-treated group compared with the control and other treated groups. In conclusion, acrylamide induced oxidative stress in the rat cerebellum, and administration of CP fruit extract offered protection from its neurotoxic effects.

The inhibitory effect of Yam polysaccharides on acrylamide-induced programmed cell death in RAW 264.7 cells.

Acrylamide has been well known for its neurotoxicity, genotoxicity, carcinogenicity, etc. Recently, the immunotoxicity of acrylamide has been reported by different research groups, although the underlying mechanisms of acrylamide endangering immune systems have not been fully elucidated. In this study, mouse monocyte-macrophage cells model was used to clarify the toxic mechanism of acrylamide and the inhibitory effect of Yam polysaccharides (YPS) on acrylamide-induced damage. We found that acrylamide induced RAW 264.7 cell death in a time- and concentration-dependent manner. After acrylamide (2.0, 3.0, 4.0 mmol/L) treatment for 24 h, cell apoptosis, autophagy, and pyroptosis were observed. However, the levels of autophagy and pyroptosis decreased at a high concentration of acrylamide (4.0 mmol/L). Acrylamide upregulated P2X7 expression, but the P2X7 level was not showing a monotone increasing trend. When the P2X7 antagonist was applied, the effect of acrylamide on autophagy and pyroptosis was weakened. Additionally, acrylamide triggered the occurrence of oxidative stress and a decreased nitric oxide (NO) level. However, reactive oxygen species (ROS) generation, the decrease of heme oxygenase-1 (HO-1) expression, and the increase of inducible nitric oxide synthase (iNOS) expression were reversed by the inhibition of P2X7. Yam polysaccharides (50.0μg/ml) significantly inhibited acrylamide-induced oxidative stress and cell death (including apoptosis, autophagy, and pyroptosis). Yam polysaccharides also effectively reversed the increase of iNOS expression induced by acrylamide. However, Yam polysaccharides promoted the expression of P2X7 rather than prohibit it. These results indicated that acrylamide caused RAW 264.7 cell death due to pro-apoptosis as well as excessive autophagy and pyroptosis. Apoptosis might be more predominant than autophagy and pyroptosis under a higher concentration of acrylamide (4.0 mmol/L). P2X7-stimulated oxidative stress was responsible for acrylamide-induced programmed cell death (PCD), but P2X7 showed limited regulatory effect on apoptosis. Yam polysaccharides with antioxidant activity inhibited acrylamide-induced cell death (apoptosis, autophagy, and pyroptosis), but exerted limited effect on the acrylamide-induced P2X7 expression. These findings would offer an insight into elucidating the immunotoxic mechanism of acrylamide and the potential approaches to control its toxicity.

Lepidium meyenii Walp (red maca) Supplementation Prevents Acrylamide-Induced Oxidative Stress and Liver Toxicity in Rats: Phytochemical Composition by UHPLC-ESI-MS/MS.

Lepidium meyenii Walp (red maca) is a high Andean plant cultivated since the Incas and has innumerable therapeutic properties. The study aims to identify its phytochemical composition using UHPLC-ESI-MS/MS, and evaluate its effects on acrylamide-induced oxidative stress. The lyophilized aqueous extract of red maca (LAqE-RM) was orally administered in doses of 1 and 2g/kg body weight for 4weeks. Malondialdehyde (MDA) levels in erythrocytes, brain, and liver, as well as hepatic levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Administration of acrylamide for 2 and 4weeks significantly increased (p < 0.001) MDA levels in erythrocytes, brain, and liver. However, LAqE-RM prevented (p < 0.001) an increase in MDA levels in all tissues studied. Likewise, the groups treated with LAqE-RM presented significantly (p < 0.001) lower levels of ALT and AST compared to the control. Treatment with LAqE-RM ameliorated the acrylamide-induced oxidative stress by reducing MDA levels in erythrocytes, brain, and liver and by lowering liver levels of ALT and AST in a dose-dependent manner. Twenty-five secondary metabolites were identified and characterized from LAqE-RM based on UHPLC mass spectrophotometry. These include carbolines, alkamides, fatty acids, and macamides, which are probably involved in their antioxidant protective role.

Blueberry Anthocyanins Extract Attenuates Acrylamide-Induced Oxidative Stress and Neuroinflammation in Rats.

Acrylamide (AA) is a widespread environmental and dietary-derived neurotoxin, which can induce oxidative stress and associated inflammation in the brain. Anthocyanins widely occur as natural antioxidant and anti-inflammatory phytochemicals. Herein, the protective effects of blueberry anthocyanins extract (BAE) against AA-induced neurotoxicity were investigated in rats. The rats were pretreated with BAE (175 mg/kg body weight/day) by oral gavage for the first 7 days, followed by the co-administration of BAE and AA (35 mg/kg body weight/day) by oral gavage for the next 12 days. Results showed that BAE significantly decreased the malondialdehyde (MDA) production, and increased glutathione (GSH) and antioxidant enzyme levels; and it also suppressed microglial activation, astrocytic reaction, and pro-inflammatory cytokine expressions. Furthermore, BAE elevated the extracellular signal-related kinase (ERK)/cAMP response elements binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway, and relieved the accumulation of amyloid beta (Aβ) 1-42 and 1-40 after AA exposure. Consequently, AA-induced neuronal necrosis and downregulation of synaptosomal-associated protein 25 (SNAP-25) were attenuated by BAE in the hippocampus and cerebral cortex. In conclusion, BAE can exert a protective function on neurons and synapses against AA-induced oxidative stress and neuroinflammation.

ETHANOL EXTRACT OF Basella alba Linn MODULATES ACRYLAMIDE-INDUCED OXIDATIVE STRESS IN WISTAR RATS

Acrylamide (AA), a common toxicant in processed foods is associated with cancer development via induction of oxidative stress. Therefore, the need for a potent antioxidant substance or compound that could ameliorate this toxic effect. Basella alba has been reported to have medicinal properties, and in this study, the anti-oxidative potentials of ethanol leaf extract of Basella alba (ELEBa) were assessed against oxidative stress induced by acrylamide in male Wistar rats (120-150g). Twenty (20) animals were grouped into four. Group 1: 1 ml/kg body weight (bwt.) distilled water (control), Group 2: 17.5 mg/kg bwt AA, Group 3: 17.5 mg/kg bwt AA+100 mg/kg bwt ELEBa, Group 4: 17.5 mg/kg bwt AA + 250 mg/kg bwt ELEBa. Treatment of animals was done orally and once daily for 14 days before sacrifice. The liver and kidney tissues were processed for the analyses of antioxidant activities. Serum was analyzed for hepatic and renal function bio markers in the treated animals. The plant’s bio active constituents were characterized by GC-MS. Acrylamide caused a significant (p &lt; 0.05) ameliorated these values. GC/MS analysis revealed the presence of pentadecanoic acid, n‐hexadecanoic acid, cis‐13-octadecenoic acid, cis-vaccenic acid, oleic acid and octadecanoic acid. Our findings suggest that, ELEBa is a potential chemopreventive agent against acrylamide-induced oxidative stress in wistar rats.

Hydroxyl containing benzo[b]thiophene analogs mitigates the acrylamide induced oxidative stress in the zebrafish larvae by stabilizing the glutathione redox cycle

AimsThis study aims to elucidate a systematic free-radical quenching ability of synthesized benzo[b]thiophene derivatives using in vitro assays and acrylamide induced oxidatively stressed model in zebrafish larvae. Materials and methodsAntioxidant activity of the compounds was evaluated using in vitro methods. The toxicity of the compounds was evaluated in Madin-Darby Canine Kidney (MDCK) cell line and zebrafish embryos. Oxidative stress was generated by acrylamide (1 mM) in zebrafish larvae and treated with compounds to evaluate the in vivo antioxidant ability. Specific fluorescence dyes were used to detect ROS generation, lipid peroxidation, and cell death followed by gene expression using RT PCR. Density functional theory (DFT) and in silico pharmacokinetics were also studied. Key findingsCompound BP and EP have a greater in vitro free radical scavenging ability. The maximum tolerated concentration (MTC) of the compounds in zebrafish larvae is 80 μM. The antioxidant system in zebrafish larvae was dysregulated due to acrylamide exposure and improvement was found while treating acrylamide exposed larvae with compounds 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP). Compound BP and EP enhanced the SOD and CAT activity, reduced the ROS and lipid peroxidation level, thus decreasing cell death in zebrafish larvae. Compound BP and EP also improved the glutathione redox cycle by stabilizing glutathione-related gene expressions. SignificanceHydroxyl-containing compounds BP and EP are promising lead molecules for pathological conditions related to oxidative stress, which showed an attenuated effect on acrylamide-induced oxidative stress in zebrafish larvae by enhancing the glutathione redox cycle and enzymatic antioxidants.

Taify Pomegranate Juice (TPJ) Abrogates Acrylamide-Induced Oxidative Stress Through the Regulation of Antioxidant Activity, Inflammation, and Apoptosis-Associated Genes.

Acrylamide (ACR) has various effects on biological systems, including oxidative stress and its associated metabolic disorders. Previous research reports that plants growing at high altitude have a different profile of antioxidants. In the current report, the Taify pomegranate juice (TPJ) of the Taify pomegranate growing at the Taif region (high altitude), Saudi Arabia, was investigated for its protective activity from ACR-induced oxidative stress. Rats were treated with ACR, TPJ, or TPJ+ACR, and various assays, including blood chemistry, liver function biomarkers, gene expression of endogenous antioxidant enzymes, oxidative stress regulatory genes, inflammation biomarkers, and apoptosis, were estimated using biochemical, real-time PCR, histopathological, and immunohistochemical analysis. TPJ showed a protective function of ACR-induced alteration of AST, ALT, GGT, urea, total proteins, albumin, MDA, and NO. It also increased the level of the endogenous antioxidative enzymes, including SOD, catalase, and GSH. It showed anti-inflammatory activity by reduction the TNF-α, IL-6 secretion and the enhancing of IL-10 levels. At the gene expression level, TPJ upregulated the expression of endogenous antioxidant genes (SOD and catalase) and of antioxidant-regulating genes Nrf2 and HO-1; downregulated the expression of inflammatory genes TGF-β1, COX2, and the apoptotic gene caspase-3; and upregulated the expression of antiapoptotic gene Bcl2. At the histological level, TPJ showed a protective effect from the ACR-induced hepatic histological damage. Results of this study conclude that TPJ has a protective effect from ACR-induced oxidative stress and its associated metabolic alterations through its antioxidant and anti-inflammatory activities.

Protective efficacy of rutin against acrylamide-induced oxidative stress, biochemical alterations and histopathological lesions in rats.

Acrylamide is a well-known neurotoxicant and carcinogen. Apart from industrial exposure, acrylamide is also found in different food products. The present study deals with in vivo experiment to test the protective effect of rutin against acrylamide induced toxicity in rats. The study was carried out on female rats with exposure of acrylamide at the dose of 38.27mg/kg body weight, orally for 10days followed by the therapy of rutin (05, 10, 20 and 40mg/kg orally), for three consecutive days. All animals were sacrificed after 24h of last treatment and various biochemical parameters in blood and tissue were investigated. Histopathology of liver, kidney and brain was also done. On administration of acrylamide for 10days, neurotoxicity was observed in terms of decreased acetylcholinesterase activity and oxidative stress was observed in terms of increased lipid peroxidation, declined level of reduced glutathione, antioxidant enzymes (superoxide dismutase and catalase) in liver, kidney and brain. Acrylamide exposure increased the activities of serum transaminases, lipid profile, bilirubin, urea, uric acid and creatinine in serum indicating damage. Our experimental results conclude that rutin showed remarkable protection against oxidative DNA damage induced by acrylamide, which may be due to its antioxidant potential.

ETHANOL EXTRACT OF Basella alba Linn MODULATES ACRYLAMIDE-INDUCED OXIDATIVE STRESS IN WISTAR RATS

Acrylamide (AA), a common toxicant in processed foods is associated with cancer development via induction of oxidative stress. Therefore, the need for a potent antioxidant substance or compound that could ameliorate this toxic effect. Basella alba has been reported to have medicinal properties, and in this study, the anti-oxidative potentials of ethanol leaf extract of Basella alba (ELEBa) were assessed against oxidative stress induced by acrylamide in male Wistar rats (120-150g). Twenty (20) animals were grouped into four. Group 1: 1 ml/kg body weight (bwt.) distilled water (control), Group 2: 17.5 mg/kg bwt AA, Group 3: 17.5 mg/kg bwt AA+100 mg/kg bwt ELEBa, Group 4: 17.5 mg/kg bwt AA + 250 mg/kg bwt ELEBa. Treatment of animals was done orally and once daily for 14 days before sacrifice. The liver and kidney tissues were processed for the analyses of antioxidant activities. Serum was analyzed for hepatic and renal function bio markers in the treated animals. The plant’s bio active constituents were characterized by GC-MS. Acrylamide caused a significant (p < 0.05) ameliorated these values. GC/MS analysis revealed the presence of pentadecanoic acid, n‐hexadecanoic acid, cis‐13-octadecenoic acid, cis-vaccenic acid, oleic acid and octadecanoic acid. Our findings suggest that, ELEBa is a potential chemopreventive agent against acrylamide-induced oxidative stress in wistar rats.

Testing the Effects of Cinnamon Extract Supplementation on Inflammation and Oxidative Stress Induced by Acrylamide.

We investigated the effects of cinnamon water extract supplementation on inflammation and oxidative stress induced by acrylamide in rats. This revealed acrylamide-intoxicated control group had significant higher levels of malondialdehyde, tumor necrosis factor-alpha (TNF-α), high-sensitive C-reactive protein (hs-CRP), leptin and alanine transaminase, and lower levels of total antioxidant capacity compared to the negative control group. In contrast, cinnamon extract administration remedied the levels of total antioxidant capacity, malondialdehyde, TNF-α, hs-CRP, and leptin in the treatment groups. However, there was no significant effect on adiponectin or liver enzymes. This chapter presents a protocol involving production of the acrylamide-induced oxidative stress model, the aqueous extraction of cinnamon powder, and measurement of inflammatory and oxidative stress markers.

Protective Effect of Triphala against Oxidative Stress-Induced Neurotoxicity.

Background Oxidative stress is implicated in the progression of many neurological diseases, which could be induced by various chemicals, such as hydrogen peroxide (H2O2) and acrylamide. Triphala is a well-recognized Ayurvedic medicine that possesses different therapeutic properties (e.g., antihistamine, antioxidant, anticancer, anti-inflammatory, antibacterial, and anticariogenic effects). However, little information is available regarding the neuroprotective effect of Triphala on oxidative stress. Materials and Methods An in vitro H2O2-induced SH-SY5Y cell model and an in vivo acrylamide-induced zebrafish model were established. Cell viability, apoptosis, and proliferation were examined by MTT assay, ELISA, and flow cytometric analysis, respectively. The molecular mechanism underlying the antioxidant activity of Triphala against H2O2 was investigated dose dependently by Western blotting. The in vivo neuroprotective effect of Triphala on acrylamide-induced oxidative injury in Danio rerio was determined using immunofluorescence staining. Results The results indicated that Triphala plays a neuroprotective role against H2O2 toxicity in inhibiting cell apoptosis and promoting cell proliferation. Furthermore, Triphala pretreatment suppressed the phosphorylation of the mitogen-activated protein kinase (MARK) signal pathway (p-Erk1/2, p-JNK1/2, and p-p38), whereas it restored the activities of antioxidant enzymes (superoxide dismutase 1 (SOD1) and catalase) in the H2O2-treated SH-SY5Y cells. Consistently, similar protective effects of Triphala were observed in declining neuroapoptosis and scavenging free radicals in the zebrafish central neural system, possessing a critical neuroprotective property against acrylamide-induced oxidative stress. Conclusion In summary, Triphala is a promising neuroprotective agent against oxidative stress in SH-SY5Y cells and zebrafishes with significant antiapoptosis and antioxidant activities.

Allicin alleviates acrylamide-induced oxidative stress in BRL-3A cells

AimAcrylamide (AA) is a common heat-generated toxicant in some food. Inhibiting its formation with natural antioxidants is of great significance. The current study aims to investigate the alleviative effect and the underlying mechanism of allicin against AA-induced oxidative stress in BRL-3A cells. Main methodsBRL-3A cells were pretreated with allicin at different concentrations for 2 h, followed by AA treatment. Cell viability was determined by Cell Counting kit-8 (CCK-8). Intracellular reactive oxygen species (ROS) status was measured using the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) method. Levels of oxidative stress markers were determined by measuring total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and 8-hydroxy-desoxyguanosine (8-OHdG) using commercial kits. Expression of the mitogen-activated protein kinase (MAPK) pathway-related proteins was determined by Western blotting. Key findingsAllicin markedly mitigated oxidative and DNA damage by increasing the activities of SOD and GSH-Px and decreasing the levels of ROS and 8-OHdG. Concomitant with these biochemical parameters, pretreatment with allicin reversed the impact of AA on the expression of p-JNK, p-ERK1/2 and p-p38. Allicin combined with SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor) enhanced cell viability in the presence of AA, as opposed to SCH772984 (ERK inhibitor). Notably, allicin ameliorated the expression of KGF, Gadd45a, c-Fos, Dusp5 and Phospholipase A2, which were related to liver injury. SignificanceCollectively, these findings demonstrate that allicin exerts protective effects against AA-induced oxidative stress by modulating the MAPK signaling pathway in BRL-3A cells.

Protective effect of citrus lemon on inflammation and adipokine levels in acrylamide-induced oxidative stress in rats

The high exposure to acrylamide (AA) due to smoking and increased consumption of processed and fast foods in recent years, has become one of the health threatening problems. This study examined the effect of lemon juice on inflammation and adipokines in acrylamide-induced oxidative stress in rats. Forty animals were divided into five groups. Toxicity was induced by AA (35mg/kg) for two weeks in all groups except normal control group. After that, lemon juice in three doses was administrated to treatment groups for 4 weeks. Serum levels of adipokines and inflammatory parameters and both serum and liver levels of oxidative stress parameters were measured. The results showed groups were received AA had significant higher levels of malondialdehyde, tumor necrosis factor alpha, leptin and C-reactive protein and lower levels of total antioxidant capacity compared to the negative control group. Lemon juice in all three doses significantly improved serum levels of TAC, MDA, TNFα and hs-CRP in treated groups. Also, 7.5 ml/kg lemon juice significantly decreased leptin levels. However, lemon juice had no significant effect on adiponectin levels. This study suggests lemon juice as a potential dietary alternative could attenuate leptin levels and manage oxidative and inflammatory damages in acrylamide- induced toxicity in rats.

Potential Protective Role of Selenium on Acrylamide-Induced Oxidative Stress in Rats: A Biochemical, Histopathological Study

Acrylamide (ACR) is an essential chemical which is extensively used in many industries and also in laboratories such as treatment of drinking water, waste water and soil, production of paper, and polishes, used as an additive in some cosmetics, used in electrophoresis and in dentistry for preparation of alloys; it is known as possible carcinogenic compound. French fries, commercially common chips and all carbohydrate containing diet are rich in acrylamide. In this study when Acrylamide is taken into the body, we investigated its toxic effect on body organs and investigated the protective role of selenium. Aim: The aim of this work is to detect acrylamide effects on liver and kidney of adult male albino rats and assess the protective role of selenium. Material and methods: Acrylamide was administrated orally at dose of (15 mg/kg body weight) (1/10 LD 50) daily for 8 weeks. Biochemical parameters in serum were studied: aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), total protiens, Albumin, Globulin, urea, creatinine, and uric acid. Liver and kidneys will be examined by light microscope to evaluate histopathological changes. Tissue malondialdehyde (MDA) was done. Results: The results after being statistically analyzed and tabulated revealed that oral Acrylamide adminstration showed a highly significant (P<0.001) elevation in aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), a highly significant (P<0.001) decrease in serum total protiens, albumin, globulin and highly significant (P<0.001) decrease in serum urea, creatinine, and uric acid levels comparing to control group. Light microscope examination of the hepatic tissue in acrylamide treated group showed obvious congestion associated with wide spread marked vacuolar degeneration as well as foci of spotty necrosis and kidneys showed marked congestion, marked hydropic degeneration of tubular epithelium and focal prominent tubular necrosis. There was a highly significant (P<0.001) increase in malondialdehyde level in acrylamide treated group comparing to control group. Selenium administration in addition to acrylamide showed significant decrease in aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), significant elevation in serum total protiens, albumin, globulin and significant increase in serum urea, creatinine, and uric acid levels comparing to acrylamide treated group. There was significant decrease in malondialdehyde level in acrylamide+sodium selenite treated group comparing to acrylamide treated group

The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats

Acrylamide (ACR) is a hazardous substance associated with the accumulation of excessive reactive oxygen species and causes oxidative stress. Presence of ACR in foods leads to public health concerns due to its known neurotoxic, genotoxic, and carcinogenic effects. The present study investigated the ameliorative effects of boron (B) against ACR exposed rats. Forty Wistar albino male rats, fed with low-boron diet, were randomly and equally allocated into 5 groups. The control group was orally treated with physiological saline as placebo, the second group was orally given 15 mg/kg ACR. The other groups were orally treated with 15 mg/kg ACR and B at the levels of 5, 10, and 20 mg/kg/day for 60 days, respectively. ACR-treatment significantly increased malondialdehyde levels whereas decreased glutathione levels in rat tissues. Also, ACR-treatment increased the activities of superoxide dismutase and catalase in erythrocytes and tissues. Meanwhile, mRNA expression levels of NFĸB, IFN-γ, IL-1β, and TNF-α in liver and brain of rats were increased under ACR treatment. Additionally, ACR caused a significant decrease in the level of high-density lipoprotein, with increase in the levels of low-density lipoprotein, triglyceride, cholesterol, glucose, urea nitrogen, and creatinine. Lastly, B alleviated histopathological alterations induced by ACR in rat tissues.

Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: Involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by MAPKs

Acrylamide (ACR) is a classic neurotoxin in animals and humans. However, the mechanism underlying ACR neurotoxicity remains controversial, and effective prevention and treatment measures against this condition are scarce. This study focused on clarifying the crosstalk between the involved signaling pathways in ACR-induced oxidative stress and inflammatory response and investigating the protective effect of antioxidant N-acetylcysteine (NAC) against ACR in PC12 cells. Results revealed that ACR exposure led to oxidative stress characterized by significant increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels and glutathione (GSH) consumption. Inflammatory response was observed based on the dose-dependently increased levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). NAC attenuated ACR-induced enhancement of MDA and ROS levels and TNF-α generation. In addition, ACR activated nuclear transcription factor E2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling pathways. Knockdown of Nrf2 by siRNA significantly blocked the increased NF-κB p65 protein expression in ACR-treated PC12 cells. Down-regulation of NF-κB by specific inhibitor BAY11-7082 similarly reduced ACR-induced increase in Nrf2 protein expression. NAC treatment increased Nrf2 expression and suppressed NF-κB p65 expression to ameliorate oxidative stress and inflammatory response caused by ACR. Further results showed that mitogen-activated protein kinases (MAPKs) pathway was activated prior to the activation of Nrf2 and NF-κB pathways. Inhibition of MAPKs blocked Nrf2 and NF-κB pathways. Collectively, ACR activated Nrf2 and NF-κB pathways which were regulated by MAPKs. A crosstalk between Nrf2 and NF-κB pathways existed in ACR-induced cell damage. NAC protected against oxidative damage and inflammatory response induced by ACR by activating Nrf2 and inhibiting NF-κB pathways in PC12 cells.

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.

Hepatoprotective effect of taurine and coenzyme Q10 and their combination against acrylamide-induced oxidative stress in rats

Purpose: To clarify the protective effects of Taurine (TA) and Coenzyme Q10 (CoQ10) for mitigation of acrylamide- induced oxidative damage. . Method: Acrylamide (AA), TA and CoQ10 were administered orally to rats for 2 and 4 weeks. Sixty albino rats of either sex weighing 200 ± 5 were randomly divided into five groups; control group, AA group, AA+ TA group, AA+ CoQ10 group and AA+ TA+ CoQ10 Group ( 15, 500 and 200 mg/kg/day dose, respectively). Hepatoprotection was assessed. The level of hepatic marker enzymes including serum lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) were evaluated. The proinflammatory cytokines including serum levels of tumor necrosis factor-α (TNF- α), interleukin- 1β (IL- 1β) and interleukin-6(IL-6) were assessed. The levels of reduced glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) in liver homogenate were also performed. Results: TA or CoQ10 significantly decreased ( p < 0.05) the elevation of hepatic markers (LDH, AST and ALT) induced by AA in rats. Reduction of serum proinflammatory cytokines (TNF-α, IL- 1β and IL-6) were also observed compared to AA group, and it was a time-effect relationship. Treatment with TA or CoQ10 also significantly reduced the oxidative stress induced by AA as shown by an increase in GSH level, and reduction of MDA level and MPO activities compared to rats treated with AA alone ( p < 0.05). The hepatoprotective effect of both TA and CoQ10 combination was more efficient than the effect of either of them alone. Conclusion: The combination of TA and Co Q10 possesses a good potential to inhibit oxidative stress from liver and also exhibits anti-inflammatory activity. Thus, they have the potential to be used to mitigate AA- induced liver injury. Keywords: Taurine, Coenzyme Q10, Acrylamide, Oxidative stress, Biochemical profile, Proinflammatory cytokines