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Andrological causes of recurrent implantation failure
Published in Efstratios M. Kolibianakis, Christos A. Venetis, Recurrent Implantation Failure, 2019
Chrisanthi Marakaki, Georgios A. Kanakis, Dimitrios G. Goulis
Acrylamide and glycidamide (a reactive epoxide metabolite from acrylamide) are industrial chemicals that are used in several ways, such as the production of polyacrylamides for wastewater treatment, textiles, paper processing, and cosmetics. Acrylamide is also a product formed in certain foods prepared at high-temperature frying, baking, or roasting, such as fried potatoes, bakery products, and coffee, and has been associated with a decrease in sperm count, motility, and morphology. Acrylamide has been shown to induce disruption or breakage of chromosomes, whereas glycidamide has mutagenic effects.78,79 There no studies on the effects of these compounds on RIF but low-dose chronic exposure is proposed to cause mutations without affecting the fertilization capacity of sperm or leading to deaths in the offspring, therefore allowing these mutations to be inherited.78
Developmental Aspects of Children’s Pharmacokinetics
Published in John C. Lipscomb, Edward V. Ohanian, Toxicokinetics and Risk Assessment, 2016
Gary Ginsberg, Dale Hattis, Babasaheb Sonawane
Several case studies with environmental toxicants have recently been reported (16–18,85). An extensive analysis by Clewell et al. (16) used PBPK modeling to simulate internal exposures to parent compound and metabolite for a range of toxicants with differing physicochemical properties: isopropanol (water soluble, volatile), vinyl chloride and methylene chloride (lipophilic, volatile), perchlorethylene (lipophilic, volatile, poorly metabolized), tetrachlorodibenzo-p-dioxin (TCDD) (lipophilic, nonvolatile, poorly metabolized), and nicotine (water soluble, nonvolatile). Internal dosimetry was simulated across a wide range of ages from birth to 75. The results suggested that for most comparisons, infants less than six months of age had internal exposure of parent compound or metabolite that was within three-fold of the dose simulated for 25-year-old adults. This is consistent with a PBPK children’s modeling effort for acrylamide and its active metabolite glycidamide (85). Due to the likely deficiency in GSH-mediated detoxification of both acrylamide and glycidamide, one may have anticipated considerably greater dosimetry in early life. However, the concomitant deficiency in the activating enzyme, CYP2E1, led to only modest differences in internal dose projections relative to adults. Other modeling case studies in children have involved inhaled solvents (17,18). In these simulations, PBPK models were adjusted for children’s physiology, but not for the ontogeny of metabolic systems.
The Role of Genetic Variants in the Association between Dietary Acrylamide and Advanced Prostate Cancer in the Netherlands Cohort Study on Diet and Cancer
Published in Nutrition and Cancer, 2018
Andy Perloy, Leo J. Schouten, Piet A. van den Brandt, Roger Godschalk, Frederik-Jan van Schooten, Janneke G. F. Hogervorst
A number of mechanisms may explain the effect of acrylamide on cancer risk (11). The first mechanism involves glycidamide, an epoxide metabolite of acrylamide. Glycidamide forms DNA adducts and is therefore thought to be the carcinogenic compound in acrylamide-induced carcinogenesis due to its genotoxicity (12). Second, in previous analyses by our group (8, 13), findings with hormone-related cancers support the hypothesis of a hormonal mechanism of acrylamide. A third mechanism is acrylamide-induced oxidative stress. Oxidative stress occurs when reactive oxygen species (ROS), generated by pro-oxidants, outbalance the antioxidant system (14). This imbalance becomes more common with increasing age (15) and may therefore play an important role in the development and progression of age-related cancers including prostate cancer (16). However, it is unclear whether and how these mechanisms may provide a causal explanation for the association between acrylamide and prostate cancer.
Protective effect of rutin against brain injury induced by acrylamide or gamma radiation: role of PI3K/AKT/GSK-3β/NRF-2 signalling pathway
Published in Archives of Physiology and Biochemistry, 2018
Noura M. Thabet, Enas M. Moustafa
It was supported by evidence that acrylamide exposure may cause hazardous effects in various tissues and systems due to its strong electrophilic nature and its metabolism to the genotoxic metabolite glycidamide (a reactive epoxide). Besides these, during metabolization ROS are generated. Both acrylamide and glycidamide are reactive compounds conjugated with glutathione and form adducts with proteins. Glycidamide, in the contrary to acrylamide is mutagenic and also forms adducts with the DNA bases (Olesen et al.2008, Özturan-Özer et al.2014). Therefore, the significant increase observed in MDA levels of the brain could be attributed to acrylamide induced apoptosis in neurons, astrocytes and reduced the proliferation of neural progenitor cells via ROS, which has an important role in the toxicity of acryl (Motamedshariaty et al.2014). Furthermore, several studies reported that, a significant increase in MDA and decrease of GSH contents, superoxide dismutase, catalase and GST activities due to the oxidative stress induced by acrylamide on membrane polyunsaturated fatty acids (PUFAs) in rat’s stomach, brain, liver and kidney (Alturfan et al.2012, Sadek 2012). In the study of Alturfan et al. (2012), the plasma TNF-α, IL-1β, IL-6, and IL-10 levels were significantly displayed increased with acrylamide-induced oxidative stress in rats. Moreover, Chen et al. (2014) revealed that acrylamide exposure contributes to neurodegenerative diseases and/or to influence neural development via interfering with NGF stimulation of the neuronal differentiation of PC12 cells through inhibition of PI3K/AKT signalling, along with the production of ROS. Additionally, this results are confirmed by the histopathological findings following acrylamide administration which are in agreement with the results of Rawi et al. (2012) study who reported that acrylamide causes changes varying from focal gliosis in the cerebral cortex and cerebrum, focal hemorrhage in the meninges and vacuolization was detected in cerebral cortex, cerebrum, cerebellum and medulla oblongata.
Analysis of the acrylamide in breads and evaluation of mitochondrial/lysosomal protective agents to reduce its toxicity in vitro model
Published in Toxin Reviews, 2022
Ahmad Salimi, Rafat Pashaei, Shahab Bohlooli, Mehrdad Vaghar-Moussavi, Jalal Pourahmad
Acrylamide a chemical agent with low molecular weight is readily solvable in water and can rapidly polymerize (Klaunig 2008). Acrylamide is quickly absorbed and emerges everywhere in the body (Klaunig 2008). Cytochrome p450 subtype CYP2E1 oxidizes acrylamide to its epoxide glycidamide in humans and rodents (Ghanayem et al.2005). Both acrylamide and glycidamide emerge to be evenly spread between the organs in animal models (Von Tungeln et al.2012). Glutathione conjugation is the main detoxification mechanism for both acrylamide and glycidamide, and also glycidamide is detoxified by hydrolysis (Kopp and Dekant 2009). There are several investigations that indicated glycidamide has genotoxic properties in both in vitro and in vivo models (Dearfield et al.1995, Klaunig 2008). Acrylamide has been proved to be a tumorigenic agent at several organ sites in rodent studies (Klaunig 2008). Cancer risk in people who were exposed occupationally to acrylamide has been reported by epidemiologic studies (Mucci and Wilson 2008). Workers who were exposed to acrylamide productions have been evaluated, and cancer occurrence in these workers has been reported (Marsh et al.1999). Glycidamide as a very reactive epoxide metabolite, can react with DNA as well as interact quickly with SH groups in proteins (Von Tungeln et al.2012). Adduct formation of acrylamide with DNA has also been reported in mice and rats (Von Tungeln et al.2012). The guanine-acrylamide DNA adduct emerges to be traceable in numerous tissues following exposure to acrylamide (Von Tungeln et al.2012). However, there is no formation about DNA adduct of acrylamide after exposure in humans (Besaratinia and Pfeifer 2005). The genotoxicity studies of acrylamide and its metabolites have been investigated extensively. The acrylamide molecule did not induce gene mutations without metabolic activation by CYP2E1, in contrast, glycidamide induces gene mutations without metabolic activation (Koyama et al.2006). After the presentation of acrylamide as a plausible human carcinogen, many epidemiological studies have investigated food exposure to acrylamide in association with the risk of cancer. The combination of experimental and toxicological studies is the primary evidence on the relation between acrylamide and cancer risk in the human diet (Mucci and Adami 2009).