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Sepsis not only leads to short-term mortality during hospitalization, but is also associated with increased mortality during long-term follow-up after hospital discharge. Metabolic stress during sepsis may cause oxidative damage to both nuclear and mitochondrial DNA (mtDNA) and RNA, which could affect long-term health and life span. Therefore, the aim of this study was to assess the association of sepsis with oxidized nucleobases and (mt)DNA damage and long-term all-cause mortality in septic patients. 91 patients with sepsis who visited the emergency department (ED) of the University Medical Center Groningen between August 2012 and June 2013 were included. Urine and plasma were collected during the ED visit. Septic patients were matched with 91 healthy controls. Death rate was obtained until June 2020.The degree of oxidation of DNA, RNA and free nucleobases were assessed in urine by mass-spectrometry. Lipid peroxidation was assessed in plasma using a TBAR assay. Additionally, plasma levels of mtDNA and damage to mtDNA were determined by qPCR. Sepsis patients denoted higher levels of oxidated DNA, RNA, free nucleobases and lipid peroxidation than controls (all p < 0.01). Further, sepsis patients displayed an increase in plasma mtDNA with an increase in mtDNA damage compared to matched controls (p < 0.01). Kaplan meier survival analyses revealed that high degrees of RNA- and nucleobase oxidation were associated with higher long-term all-cause mortality after sepsis (p < 0.01 and p = 0.01 respectively). Of these two, high RNA oxidation was associated with long-term all-cause mortality, independent of adjustment for age, medical history and sepsis severity (HR 1.29 [(1.17–1.41, 95% CI] p < 0.01). Sepsis is accompanied with oxidation of nuclear and mitochondrial DNA and RNA, where RNA oxidation is an independent predictor of long-term all-cause mortality. In addition, sepsis causes mtDNA damage and an increase in cell free mtDNA in plasma. Sepsis leads to mitochondrial DNA damage and oxidized nucleobases which is associated long-term all-cause mortality. Sepsis causes an induction of reactive oxygen species (ROS) which are produced by the mitochondria. DNA, RNA and lipids in mitochondria and cells are damaged by ROS. Both oxidized DNA and RNA are associated with long-term all-cause mortality. [Display omitted] [ABSTRACT FROM AUTHOR]

Phthalates are substances used as plasticizing agents and solvents that can increase the risk of infertility and that appear to induce oxidative stress. The aim of the study was to show the possible relationship between urinary concentrations of phthalates metabolites, namely MEP, MBzP, MnBP, MEHP, MEHHP, and MnOP and biomarkers of nucleic acids oxidation, methylation, or protein nitroxidation. The oxidative stress biomarkers measured in human urine were 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, 8-oxo-7,8-dihydro-2′-deoxyguanosine, 3-nitrotyrosine, and 5-methylcytidine. Two hundred and seventy-four couples were enrolled, undergoing an assisted reproduction technology (ART) treatment, urine samples were analyzed in HPLC/MS-MS, and then two sub-groups with urinary concentration > 90th or 2Tyr between men and women, with higher levels in men, was found. The levels of oxidative stress biomarkers were directly correlated with some phthalate concentrations in both sexes.

Phthalates are substances used as plasticizing agents and solvents that can increase the risk of infertility and that appear to induce oxidative stress. The aim of the study was to show the possible relationship between urinary concentrations of phthalates metabolites, namely MEP, MBzP, MnBP, MEHP, MEHHP, and MnOP and biomarkers of nucleic acids oxidation, methylation, or protein nitroxidation. The oxidative stress biomarkers measured in human urine were 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, 8-oxo-7,8-dihydro-2′-deoxyguanosine, 3-nitrotyrosine, and 5-methylcytidine. Two hundred and seventy-four couples were enrolled, undergoing an assisted reproduction technology (ART) treatment, urine samples were analyzed in HPLC/MS-MS, and then two sub-groups with urinary concentration > 90th or <10th percentile were identified, reducing the sample size to 112 subjects. The levels of oxidative stress biomarkers were measured in both groups, reduced to 52 men and 60 women. A statistically significantly difference for 8-oxoGuo and 3-NO2Tyr between men and women, with higher levels in men, was found. The levels of oxidative stress biomarkers were directly correlated with some phthalate concentrations in both sexes. [ABSTRACT FROM AUTHOR]

Abstract: Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone and decreased or inappropriately normal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels suggesting a functional defect in the pituitary. The molecular mechanisms behind this disorder are undefined. A role for ethanol-induced oxidative damage in the pathophysiology is supported by studies in liver, muscle, and heart of experimental animals, but there is limited evidence in the pituitary. We examined markers of oxidative damage to lipids and proteins in pituitaries from rats consuming ethanol for 5, 10, 20, 30, and 60 days in addition to markers of damage to nucleic acids in pituitaries after 60 days of ethanol exposure. There were increases in 8-oxo-deoxyguanosine immunoreactivity, a marker of oxidative damage to nucleic acids, and an overall increase in malondialdehyde and 4-hydroxynonenal, markers of lipid peroxidation. Protein carbonylation and protein nitrotyrosination, markers of protein oxidation, were significantly increased after 30 days and 60 days of ethanol consumption, respectively. After 60 days of ethanol exposure, TUNEL assay revealed that cell death in the ethanol-treated pituitaries was not significantly different from that in the pair-fed controls at the time of examination. We also measured serum testosterone, FSH, and LH after ethanol consumption for 5, 10, 20, 30, and 60 days. Through 5 to 60 days of ethanol exposure, testosterone levels were consistently lower whereas LH and FSH were inappropriately unchanged, suggesting pituitary malfunction. These results provide evidence for ethanol-induced oxidative damage at the pituitary level, which may contribute to pituitary dysfunction. [Copyright &y& Elsevier]

(1) Background: The oxidized guanine derivatives excreted into urine, products of DNA and RNA oxidation and repair, are used as biomarkers of oxidative damage in humans. This study aims to evaluate oxidative damage in gasoline pump attendants occupationally exposed to benzene. Benzene is contained in the gasoline but it is also produced from traffic and from smoking. (2) Methods: Twenty-nine gasoline pump attendants from two major cities of Saudi Arabia and 102 from Italy were studied for urinary 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and S-phenyl-mercapturic acid (SPMA) for benzene exposure and urinary cotinine for smoking status assessment by liquid chromatography-tandem mass spectrometry. Airborne benzene was also assessed in the Italian group by gas-chromatography with flame ionization detector (GC-FID). (3) Results: The results suggest that high levels of benzene exposure can cause an accumulation of SPMA and bring about the formation of the oxidation biomarkers studied to saturation. At low exposure levels, SPMA and oxidation biomarker levels were correlated among them and were associated with the smoking habit. (4) Conclusions: The study confirms the association between benzene exposure and the excretion of nucleic acid oxidation biomarkers and enhances the importance of measuring the smoking habit, as it can significantly influence oxidative damage, especially when the exposure levels are low.