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Role of Oxidative Stress in the Onset of Alzheimer’s Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Tasnuva Sarowar, Md. Hafiz Uddin
In fact, several biomarkers have been identified either in the cerebrospinal fluid (CSF) or blood of the AD patients or animal models in correlation to oxidative stress (Chen and Zhong 2014). The brain contains high amount of phospholipids, which contains ample amount of polyunsaturated fatty acids (PUFA). Oxidized PUFA gives rise to malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and F2-isoprostanes, which are biomarkers of AD (Williams et al. 2006). Similarly, protein oxidation yields protein carbonyls and 3-nitrotyrosine, which are found in the CSF of AD patients (Keller et al. 2005). DNA and RNA oxidation produce 8-hydroxyguanosine, 8-hydroxydeoxyguanosine, and DNA double-strand breaks. There is also evidence that AD brains, especially the cortex, is enriched with such oxidation products (Mecocci, MacGarvey, and Beal 1994, Mullaart et al. 1990). Additionally, altered activity of SOD and catalase have been reported in AD patients (Marcus et al. 1998). There are several mechanisms underlying oxidative stress in the pathology of AD, and these are discussed in more detail in the following parts of the chapter.
Micronutrient Supplementation and Ergogenesis — Metabolic Intermediates
Published in Luke Bucci, Nutrients as Ergogenic Aids for Sports and Exercise, 2020
Eleven trained male subjects were tested by cycle ergometry (90 min at 65% VO2max) before and after 28 d of supplementation with an antioxidant mixture (533 mg d-α-tocopherol, 1000 mg ascorbic acid, and 10 mg of ß-carotene per day).443b Measurement of urinary 8-hydroxyguanosine was used as an indicator of free radical damage (RNA oxidation). Although levels of supplemented antioxidants were increased by 87% (vitamin E), 16% (vitamin C) and 480% (ß-carotene), urinary output of 8-hydroxyguanosine was not affected by exercise before or after antioxidant supplementation. Perhaps more intense exercise is needed to exhibit exercise-induced oxidative damage to RNA in humans, and more or different antioxidants are needed to decrease measures of RNA oxidation.
Lab-on-a-Chip-Based Devices for Rapid and Accurate Measurement of Nanomaterial Toxicity
Published in Suresh C. Pillai, Yvonne Lang, Toxicity of Nanomaterials, 2019
Mehenur Sarwar, Amirali Nilchian, Chen-zhong Li
Our lab in the past has developed a novel lateral flow immunoassay (LFIA) to determine the genomic level of nanotoxicity (Zhu et al. 2013, 2014; Leichner et al. 2017). The test strip is based on five compartments: (1) sample loading zone, (2) conjugate pad, (3) test line, (4) control line, and (5) absorption pad. Each of these compartments plays an important role in terms of genotoxicity determination. To test a sample, the sample loading zone is immersed in the sample. Due to capillary force, the sample moves along the strip and reaches the conjugate pad. This movement of liquid relies on the physical properties of the material (wettability/pore size). The gold NP-tagged monoclonal antibodies (AuNPs-Abs) reside in the conjugate pad and form a complex with the biomarkers. Unbound AuNPs-Abs accumulate in the test line and forms a complex with BSA-8-hydroxyguanosine. It can be identified by a red colour change, even with the naked eye. The colour intensity is inversely proportional to the concentration of the analyte. In the control line, polyclonal goat anti-mouse IgG can bind with the unbound AuNP-Abs and tri-complex producing red line in the control zone. This phenomenon is utilized to depict that the test was performed successfully, and the sample was sufficient to flow from the starting point (sample zone) towards the test line and control line. The limit of detection of 8-OHdG was found to be 2.07 ng mL−1 in PBS on the paper fluidic device by the colorimetric method.
Utility of comet assay of DNA damage in the detection of malignant transformation of chronic liver cirrhosis
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2023
Narmin Effat Saied, Gehad Mohsen Elmazny, Rania Mostafa El-helaly, Raghda El-sayed Farag, Khaled Abd El-Wahab, Ekbal Abo Hashim, Rasha Rizk El-zehery
Two earlier studies conducted by Farinati et al. and Cardin et al., concluded that the occurrence of a significantly higher level of DNA damage, proved by identification of the 8-hydroxyguanosine level, was associated with chronic HCV infection, and was higher than in HBV infected cases [26,27]. Another study, using alkaline comet assay, reported that the degree of DNA damage was significantly increased in the PBLs of subjects with cirrhosis on top of chronic HCV and HBV, when compared with healthy participants [28]. On the other hand, absence of any elevation in the DNA alkali labile sites or single-strand breaks in the PBLs of cases with chronic hepatitis B or C was reported by other studies [29]. These variations can be explained by the variance of the study groups and the difference of hepatic status amongst studied subjects. Therefore, a large-scale study is required with strict standardized technique.
Toxic metals in cement induced hematological and DNA damage as well as carcinogenesis in occupationally-Exposed block-factory workers in Lagos, Nigeria
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Tajudeen Yahaya, Esther Oladele, Titilola Salisu, Esther Orji, Zafira Zakari, Umar Usman Liman, Clement Boniface Gomo, Mustapha Abdullahi
Ten milliliters (10 ml) of whole venous blood samples were collected in the morning after an overnight fast from each participant using a 5-ml syringe and a 20-gauge needle. Exactly 4 ml of the blood was measured into an ethylene-di-amine-tetra-acetic-acid (EDTA) bottle and used for heavy metal and hematological analyses in the laboratory. The remaining 7 ml was poured into a plain vial and centrifuged at 2500 rpm at 2°C for 20 minutes in the laboratory to separate the blood plasma. The plasma was collected in a fresh, clean tube and stored at −20°C before being used for measuring selected biomarkers of organ damage, namely albumin (ALB), glutamate dehydrogenase (GLDH), and kidney injury molecule-1 (KIM-1). As indicators of oxidative stress, DNA damage, and carcinogenicity, the total antioxidant capacity (TAC), malondialdehyde (MDA), DNA-8-hydroxyguanosine (8-OHdG), and carcinoembryonic antigen [CEA) were also measured.
Chemistry of ROS-mediated oxidation to the guanine base in DNA and its biological consequences
Published in International Journal of Radiation Biology, 2022
Aaron M. Fleming, Cynthia J. Burrows
We show in Figure 2(A,B) that three mechanisms could lead to 8-hydroxyguanosine which isomerizes to OG (Cho et al. 1990). Similarly, two analogous mechanisms, hydroxyl radical addition or hydration of G•+, could lead to hydroxylation of G at C5 rather than C8 (Figure 2(C)) (Cadet et al. 2008, 2014; Fleming and Burrows 2017a). The 5-hydroxy isomer is also an unstable intermediate; molecules of this sort are more stable as carbonyl compounds if possible, and in this case, a facile 1,2-acyl shift can occur to generate a new isomeric heterocycle, which after hydration and ring opening leads to 2Ih, first characterized by Louise Ball and coworkers (North Carolina) (Ye et al. 2009). The rearrangement, proposed initially by Genevieve Pratviel (CNRS, Toulouse) by analogy to the same rearrangement reported in our laboratory in 2000 for 5,8-dihydroxyG, leads to a spirohydantoin structure, as shown in Figure 2(C) (Luo et al. 2000; Vialas et al. 2000; Lapi et al. 2001). Because this spirocycle is not oxidized at C8 and the 5-membered ring is no longer aromatic, it undergoes a slow addition of H2O at C8, followed by ring opening to a bis-formamido-2-iminohydantoin structure, 2Ih.