Interventions targeted at oxidatively generated modifications of nucleic acids focused on urine and plasma markers

Larsen, Emil List; Weimann, Allan; Poulsen, Henrik Enghusen

doi:10.1016/j.freeradbiomed.2019.09.030

Cited by 26 publications

(20 citation statements)

References 256 publications

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“…Nucleotide oxidation is a highly abundant DNA modification [ 115 ] and represents a pre-mutagenic lesion that induces CG:TA transversion mutations, which can also contribute to cancer [ 116 ]. The guanine moiety is particularly prone to oxidation under formation of 8-hydroxy-2-deoxyguanosine (8-OHdG) or 8-OHG (8-oxoGuo) and can be used as a marker of DNA and RNA oxidation by Fenton chemistry-derived hydroxyl radicals or peroxynitrite.…”

Section: Classical “Oxidative Stress” Biomarkers In Human Cardiovascular Diseasementioning

confidence: 99%

Redox-related biomarkers in human cardiovascular disease - classical footprints and beyond

et al. 2021

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Global epidemiological studies show that chronic non-communicable diseases such as atherosclerosis and metabolic disorders represent the leading cause of premature mortality and morbidity. Cardiovascular disease such as ischemic heart disease is a major contributor to the global burden of disease and the socioeconomic health costs. Clinical and epidemiological data show an association of typical oxidative stress markers such as lipid peroxidation products, 3-nitrotyrosine or oxidized DNA/RNA bases with all major cardiovascular diseases. This supports the concept that the formation of reactive oxygen and nitrogen species by various sources (NADPH oxidases, xanthine oxidase and mitochondrial respiratory chain) represents a hallmark of the leading cardiovascular comorbidities such as hyperlipidemia, hypertension and diabetes. These reactive oxygen and nitrogen species can lead to oxidative damage but also adverse redox signaling at the level of kinases, calcium handling, inflammation, epigenetic control, circadian clock and proteasomal system. The in vivo footprints of these adverse processes (redox biomarkers) are discussed in the present review with focus on their clinical relevance, whereas the details of their mechanisms of formation and technical aspects of their detection are only briefly mentioned. The major categories of redox biomarkers are summarized and explained on the basis of suitable examples. Also the potential prognostic value of redox biomarkers is critically discussed to understand what kind of information they can provide but also what they cannot achieve.

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Section: Classical “Oxidative Stress” Biomarkers In Human Cardiovascular Diseasementioning

confidence: 99%

Redox-related biomarkers in human cardiovascular disease - classical footprints and beyond

et al. 2021

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“…The strengths of our study include 1) two independent randomised controlled trials were analysed; and 2) the application of the UPLC-MS/MS technique to measure 8-oxodG and 8-oxoGuo, which is considered the reference standard method due to the high specificity, especially when compared to the ELISA method 34 . Moreover, the measurement of oxidative stress in the urine is only minimally affected by diet and cell death, and is not influenced by long-term storage and the risk of sample oxidation during collection and storage is therefore low 14 .…”

Section: Discussionmentioning

confidence: 99%

The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes

Sivalingam

Larsen

Raalte³

et al. 2021

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Glucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (− 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (− 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.

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“…Smoking and lipid-lowering treatment are other possible confounders [46]. To exclude tentative changes in smoking status or in lipid-lowering drug intake during the time of follow up as a reason for a change in urinary marker levels, we also choose to evaluate possible differences between smokers and non-smokers as well as patients on and not on lipid-lowering drugs, by visual interpretation of graph.…”

Section: Data Analysis and Statisticsmentioning

confidence: 99%

“…A reduction in bodyweight has been reported to reduce other markers of oxidative stress [48,49], but so far, only few interventions except for smoking cessation, olive oil intake [46] and perhaps sleeve gastrectomy [14] have been able to reduce levels of urinary markers of DNA or RNA oxidation. Nevertheless, since ROS clearly play a role in pathogenesis of various diseases, (focus has been on the toxicological aspects of high levels of oxidative stress, however it is now realized that modifications in the redox balance is a multifaceted regulatory mechanism in normal physiological situations [5]), preventive and therapeutic strategies that aim to restore redox homeostasis may be an intuitive approach with a large potential to protect against metabolic diseases [3][4][5].…”

Section: Plos Onementioning

confidence: 99%

Reduction of oxidative stress on DNA and RNA in obese patients after Roux-en-Y gastric bypass surgery—An observational cohort study of changes in urinary markers

et al. 2020

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Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality risks. Levels of oxidative damage to DNA and RNA can be estimated through measurement of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine. Both markers have been associated with type 2 diabetes, where especially 8-oxoGuo is prognostic for mortality risk. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery that has considerable effects on bodyweight, hyperglycemia and mortality, might be working through mechanisms that reduce oxidative stress, thereby reducing levels of the urinary markers. We used liquid chromatography coupled with tandem mass spectrometry to analyze the content of 8-oxodG and 8-oxoGuo in urinary samples from 356 obese patients treated with the RYGB-procedure. Mean age (SD) was 44.2 (9.6) years, BMI was 42.1 (5.6) kg/m2. Ninety-six (27%) of the patients had type 2 diabetes. Excretion levels of each marker before and after surgery were compared as estimates of the total 24-hour excretion, using a model based on glomerular filtration rate (calculated from cystatin C, age, height and weight), plasma- and urinary creatinine. The excretion of 8-oxodG increased in the first months after RYGB. For 8-oxoGuo, a gradual decrease was seen. Two years after RYGB and a mean weight loss of 35 kg, decreased hyperglycemia and insulin resistance, excretion levels of both markers were reduced by approximately 12% (P < 0.001). For both markers, mean excretion levels were about 30% lower in the female subgroup (P < 0.0001). Also, in this subgroup, excretion of 8-oxodG was significantly lower in patients with than without diabetes. We conclude, that oxidative damage to nucleic acids, reflected in the excretion of 8-oxodG and 8-oxoGuo, had decreased significantly two years after RYGB—indicating that reduced oxidative stress could be contributing to the many long-term benefits of RYGB-surgery in obesity and type 2 diabetes.

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Interventions targeted at oxidatively generated modifications of nucleic acids focused on urine and plasma markers

Cited by 26 publications

References 256 publications

Redox-related biomarkers in human cardiovascular disease - classical footprints and beyond

Redox-related biomarkers in human cardiovascular disease - classical footprints and beyond

The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes

Reduction of oxidative stress on DNA and RNA in obese patients after Roux-en-Y gastric bypass surgery—An observational cohort study of changes in urinary markers

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