Reactive oxygen species (ROS) are continuously produced in living cells due to metabolic and biochemical reactions and due to exposure to physical, chemical and biological agents. Excessive ROS cause ...oxidative stress and lead to oxidative DNA damage. Within ROS-mediated DNA lesions, 8-oxoguanine (8-oxoG) and its nucleotide 8-oxo-2'-deoxyguanosine (8-oxodG)-the guanine and deoxyguanosine oxidation products, respectively, are regarded as the most significant biomarkers for oxidative DNA damage. The quantification of 8-oxoG and 8-oxodG in urine, blood, tissue and saliva is essential, being employed to determine the overall effects of oxidative stress and to assess the risk, diagnose, and evaluate the treatment of autoimmune, inflammatory, neurodegenerative and cardiovascular diseases, diabetes, cancer and other age-related diseases. High-performance liquid chromatography with electrochemical detection (HPLC-ECD) is largely employed for 8-oxoG and 8-oxodG determination in biological samples due to its high selectivity and sensitivity, down to the femtomolar range. This review seeks to provide an exhaustive analysis of the most recent reports on the HPLC-ECD determination of 8-oxoG and 8-oxodG in cellular DNA and body fluids, which is relevant for health research.
•Loss of telomere maintenance contributes ageing-related diseases and carcinogenesis.•Numerous diseases associated with oxidative stress are also associated with shortened telomeres.•Studies in human ...tissues, mouse models and cell culture provide evidence that oxidative stress accelerates telomere shortening.•Telomeres are highly sensitive to oxidative DNA damage, which can induce telomere losses and dysfunction.•Base excision repair of oxidative damage is essential for telomere maintenance.
Telomeres are dynamic nucleoprotein-DNA structures that cap and protect linear chromosome ends. Because telomeres shorten progressively with each replication, they impose a functional limit on the number of times a cell can divide. Critically short telomeres trigger cellular senescence in normal cells, or genomic instability in pre-malignant cells, which contribute to numerous degenerative and aging-related diseases including cancer. Therefore, a detailed understanding of the mechanisms of telomere loss and preservation is important for human health. Numerous studies have shown that oxidative stress is associated with accelerated telomere shortening and dysfunction. Oxidative stress caused by inflammation, intrinsic cell factors or environmental exposures, contributes to the pathogenesis of many degenerative diseases and cancer. Here we review the studies demonstrating associations between oxidative stress and accelerated telomere attrition in human tissue, mice and cell culture, and discuss possible mechanisms and cellular pathways that protect telomeres from oxidative damage.
The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination ...to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of “simple” and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks. More significant in terms of frequency are endogenous mechanisms of modification, which include hydrolytic disintegration of DNA chemical bonds, attack by reactive oxygen species and other byproducts of normal cellular metabolism, or incomplete or necessary enzymatic reactions (such as topoisomerases or repair nucleases). Both exogenous and endogenous mechanisms are associated with a high risk of single strand breakage, either produced directly or generated as intermediates of DNA repair. This review will focus upon the creation, consequences and resolution of single strand breaks, with a particular focus on two major coordinating repair proteins: poly(ADP-ribose) polymerase 1 (PARP1) and X-ray repair cross-complementing protein 1 (XRCC1).
Display omitted
•Overview of the types and consequences of prominent forms of endogenous DNA damage.•Detailed description of the structure, biochemistry and biology of PARP1 and XRCC1.•Comprehensive summary of the molecular choreography of single strand break repair.•Introduction of the link between defects in single strand break repair and neurological disease.
Due to its health benefits, resveratrol (RE) is one of the most researched natural polyphenols. Resveratrol's health benefits were first highlighted in the early 1990s in the French paradox study, ...which opened extensive research activity into this compound. Ever since, several pharmacological activities including antioxidant, anti-aging, anti-inflammatory, anti-cancerous, anti-diabetic, cardioprotective, and neuroprotective properties, were attributed to RE. However, results from the available human clinical trials were controversial concerning the protective effects of RE against diseases and their sequelae. The reason for these conflicting findings is varied but differences in the characteristics of the enrolled patients, RE doses used, and duration of RE supplementation were proposed, at least in part, as possible causes. In particular, the optimal RE dosage capable of maximizing its health benefits without raising toxicity issues remains an area of extensive research. In this context, while there is a consistent body of literature on the protective effects of RE against diseases, there are relatively few reports investigating its possible toxicity. Indeed, toxicity and adverse effects were reported following consumption of RE; therefore, extensive future studies on the long-term effects, as well as the in vivo adverse effects, of RE supplementation in humans are needed. Furthermore, data on the interactions of RE when combined with other therapies are still lacking, as well as results related to its absorption and bioavailability in the human body. In this review, we collect and summarize the available literature about RE toxicity and side effects. In this process, we analyze in vitro and in vivo studies that have addressed this stilbenoid. These studies suggest that RE still has an unexplored side. Finally, we discuss the new delivery methods that are being employed to overcome the low bioavailability of RE.
Asbestos, especially chrysotile, continues to be exposed to humans globally. Hence, it should be disposed properly to prevent asbestos-related diseases, including mesothelioma and lung cancer. This ...study aimed to verify whether forsterite, a heating product of chrysotile, can cause carcinogenicity, particularly mesothelioma. Forsterite (FO-1000) and enstatite (EN-1500) produced by heating chrysotile at 1000°C and 1500°C, respectively, were subjected. We injected 10 mg of chrysotile, FO-1000, or EN-1500 in rats intraperitoneally and observed the development of peritoneal mesothelioma until 24 months. The incidence of peritoneal mesothelioma in the chrysotile group was 91.2%, whereas in the FO-1000 and EN-1500 groups, peritoneal mesothelioma did not develop. Urinary 8-hydroxy-2′-deoxyguanosine and serum N-ERC/mesothelin concentrations significantly increased in the chrysotile group that developed peritoneal mesothelioma, while they only temporarily changed in the FO-1000 or EN-1500 groups during early treatment. Furthermore, there was a significant homozygous deletion of the CDKN2A/p16 gene in the chrysotile group compared to the control group, in contrast to no significant difference in the FO-1000 and EN-1500 groups. Therefore, this study provides clear evidence that forsterite is a nonmesothelioma carcinogen and suggests that forsterite and enstatite are sufficient substances for chrysotile detoxification.
Toxicologic studies have reported propylene oxide (PO) exposure may harm the respiratory system, but the association between PO exposure and lung function and potential mechanism remains unclear.
...What is the association between PO exposure and lung function and potential mediating mechanism?
Urinary PO metabolite N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) as PO internal exposure biomarker and lung function were measured for 3,692 community residents at baseline and repeated at 3-year follow up. Cross-sectional and longitudinal associations between urinary 2HPMA and lung function were assessed by linear mixed model. Urinary 8-hydroxy-deoxyguanosine, urinary 8-iso-prostaglandin-F2α, and plasma protein carbonyls as biomarkers of oxidative DNA damage, lipid peroxidation, and protein carbonylation, respectively, were measured for all participants to explore their potential roles in 2HPMA-associated lung function decline by mediation analysis.
After adjustment for potential covariates, each threefold increase in urinary 2HPMA was cross sectionally associated with a 26.18 mL (95% CI, −50.55 to −1.81) and a 21.83 mL (95% CI, −42.71 to −0.95) decrease in FVC and FEV1, respectively, at baseline (all P < .05). After 3 years of follow up, 2HPMA was observed to be longitudinally associated with FEV1/FVC decline. No significant interaction effect of smoking or passive smoking was observed (Pinteraction > .05), and the associations between 2HPMA and lung function indexes were persistent among participants who were not smoking and those who were not passive smoking in both baseline and follow-up evaluations. We observed urinary 8-hydroxy-deoxyguanosine partially mediated the associations of 2HPMA with FVC (mediation proportion, 5.48%) and FEV1 (mediation proportion, 6.81%), and plasma protein carbonyl partially mediated the association between 2HPMA and FEV1 (mediation proportion, 3.44%).
PO exposure was associated with lung function decline among community residents, and oxidative DNA damage and protein carbonylation partially mediated PO exposure-associated lung function decline. Further attention on respiratory damage caused by PO exposure is warranted.
Objective: To explore the possible effects of naringin on acrylamide-induced nephrotoxicity in rats. Methods: Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups. The ...control group was given intragastric (i.g.) saline (1 mL) for 10 d. The acrylamide group was given i.g. acrylamide in saline (38.27 mg/kg titrated to 1 mL) for 10 d. The treatment groups were administered with naringin in saline (50 and 100 mg/kg, respectively) for 10 d and given i.g. acrylamide (38.27 mg/kg) 1 h after naringin injection. The naringin group was given i.g. naringin (100 mg/kg) alone for 10 d. On day 11, intracardiac blood samples were obtained from the rats when they were under anesthesia, after which they were euthanized. Urea and creatinine concentrations of blood serum samples were analyzed with an autoanalyzer. Enzyme-linked immunosorbent assay was used to quantify malondialdehyde, superoxide dismutase, glutathione, glutathione peroxidase, catalase, tumor necrosis factor-β, nuclear factor-κB, interleukin (IL)-33, IL-6, IL-1β, cyclooxygenase-2, kidney injury molecule-1, mitogen-activated protein kinase-1, and caspase-3 in kidney tissues. Renal tissues were also evaluated by histopathological and immunohistochemical examinations for 8-OHdG and Bcl-2. Results: Naringin attenuated acrylamide-induced nephrotoxicity by significantly decreasing serum urea and creatinine levels. Naringin increased superoxide dismutase, glutathione, glutathione peroxidase, and catalase activities and decreased malondialdehyde levels in kidney tissues. In addition, naringin reduced the levels of inflammatory and apoptotic parameters in kidney tissues. The histopathological assay showed that acrylamide caused histopathological changes and DNA damage, which were ameliorated by naringin. Conclusions: Naringin attenuated inflammation, apoptosis, oxidative stress, and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats.
The International Agency for Research on Cancer has classified arsenic as a class I carcinogen. Oxidative DNA damage is a typical early precursor to recognized malignancies. The most sensitive early ...independent marker of oxidative DNA damage is believed to be 8-hydroxy-2 deoxyguanosine (8-OHdG). To date, research on the link between urinary arsenic and 8-OHdG has not been consistent.
This study was aimed at exploring the effects of urinary arsenic on 8-OHdG in human urine.
A literature search until January 2023 was performed on the PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases through a combination of computer and manual retrieval. Stata 12.0 was used to examine the degree of heterogeneity among included studies. The percentage change and 95 % confidence interval (95 % CI) of 8-OHdG were calculated between populations exposed to different doses. We used a random effect model because the degree of heterogeneity exceeded 50 %. Sensitivity analysis and testing for publication bias were performed.
This meta-analysis included nine studies, most of which were performed in China. After exposure to arsenic, urinary arsenic (per 10 μg/g creatinine increase) was associated with the increased 8-OHdG (% change = 41.49 %, 95 % CI: 19.73 %, 63.25 %). Subgroup analysis indicated that the percentage change in 8-OHdG in urine was more pronounced in people exposed to arsenic <50 μg/L (% change = 24.60 %, 95 % CI: 17.35 %, 37.85 %). In studies using total urinary arsenic content as an indicator, the percentage change in 8-OHdG in urine was more significant (% change = 60.38 %, 95 % CI: 15.08 %, 105.68 %).
The 8-OHdG levels in human urine significantly increased after exposure to environmental arsenic, thus suggesting that arsenic exposure is correlated with oxidative DNA damage.
Display omitted
•This is the first meta-analysis that explored the relationship between arsenic exposure and 8-OHdG in urine.•A 10 μg/g creatinine increase in arsenic was associated with a 28.10 % increase in 8-OHdG.•Exposure to arsenic can induce DNA oxidative damage in humans.
The ban of some antibacterial ingredients, such as triclosan (TCS) and triclocarban (TCC), in personal care products (PCPs) in some countries (but not in China) has resulted in the increasing use of ...antibacterial alternatives, such as chloroxylenol (PCMX). However, the underlying human health risks and environmental impacts of PCMX exposure are largely unknown. Thus, the distribution characteristics of PCMX in PCPs and susceptible populations and the major routes and health risks of human exposure to PCMX were investigated. The PCMX, TCS, and TCC concentrations in PCPs, urine, drinking water, and surface water were determined using high-performance liquid chromatograph system equipped with diode array detector or triple quadrupole mass spectrometer. Results showed that PCMX is widely used in antibacterial hand sanitizers and household disinfectants in China. The addition of PCMX as an antibacterial ingredient in PCPs showed an increasing trend. The geomean concentrations of urinary PCMX in children and pregnant women were 21.6 and 31.9 μg·L−1, respectively, which were much higher than TCS and TCC. A considerable concentration of PCMX ranging from 1.62 to 9.57 μg·L−1 was observed in the aquatic environment, suggesting a potential massive-use of PCMX by humans. Human PCMX exposure via drinking was negligible because the PCMX concentrations in drinking water were less than 2.00 ng·L−1. During human simulation experiment, we found that dermal contact was the dominant route of human PCMX exposure, accounting for 92.1% of the urinary PCMX concentration. The estimated daily intake of PCMX in 9.68% of children and 5.66% of pregnant women was higher than the reference dose. However, the urinary 8-hydroxy-2′-deoxyguanosine concentrations remained stable despite the elevated PCMX concentrations, thereby suggesting that daily PCMX exposure may not cause oxidative DNA damage in humans. Nevertheless, the potential ecotoxicity and health risks induced by chronic PCMX exposure cannot be ignored because of its increasing use.
Display omitted
•PCMX was widely used in antibacterial hand sanitizers and household disinfectants.•PCMX as an antibacterial ingredient was increasingly used in PCPs.•Dermal contact was a dominate route for human exposure to PCMX.•Urinary DNA oxidative damage level remained stable despite of elevated PCMX level.•PCMX might cause potential aquatic toxicity in the rivers of Guangzhou, China.
PDF
