Urinary 8-hydroxydeoxyguanosine Research Articles

Biomonitoring urinary pesticide metabolites in preschool children by supported liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry and their association with oxidative stress

Investigating pesticide exposure and oxidative stress in preschool children is essential for elucidating the determinants of environmental health in early life, with human biomonitoring of urinary pesticide metabolites serving as a critical strategy for achieving this objective. This study demonstrated biomonitoring of 2 phenoxyacetic acid herbicides, 2 organophosphorus pesticide metabolites, and 4 pyrethroid pesticide metabolites in 159 preschool children and evaluated their association with oxidative stress biomarker 8-hydroxydeoxyguanosine. An enzymatic deconjugation process was used to release urinary pesticide metabolites, which were then extracted and enriched by supported liquid extraction, and quantified by ultra-high performance liquid chromatography-tandem mass spectrometry with internal standard calibration. Dichloromethane: methyl tert‑butyl ether (1:1, v/v) was optimized as the solvent for supported liquid extraction, and we validated the method for linear range, recovery, matrix effect and method detection limit. Method detection limit of the pesticide metabolites ranged from 0.01 μg/L to 0.04 μg/L, with satisfactory recoveries ranging from 70.5 % to 95.5 %. 2,4,5-Trichlorophenoxyacetic acid was not detected, whereas the other seven pesticide metabolites were detected with frequencies ranging from 10.1 % to 100 %. The concentration of urinary pesticide metabolites did not significantly differ between boys and girls, with the median concentrations being 9.39 μg/L for boys and 4.90 μg/L for girls, respectively. Spearman correlation analysis indicated that significant positive correlations among urinary metabolites. Bayesian kernel machine regression revealed a significant positive association between urinary pesticide metabolites and 8-hydroxydeoxyguanosine. Para-nitrophenol was the pesticide metabolite that contributed significantly to the elevated level of oxidative stress.

Humoral immunosuppression of exposure to polycyclic aromatic hydrocarbons and the roles of oxidative stress and inflammation

Previous studies have indicated adverse health effects of exposure to polycyclic aromatic hydrocarbons (PAHs), but evidence on the association between PAH exposure and immunity is scarce and its underlying mechanism is largely unknown. This study assessed human exposure to PAHs by determining the concentrations of PAHs in serum and their metabolites in paired urine. The oxidative stress and inflammation levels were evaluated by urinary DNA damage biomarker 8-hydroxydeoxyguanosine, white blood cell counts and C-reaction protein. We investigated the relationship between PAH exposure and seven immunological components, and explored the indirect roles of oxidative stress and inflammation by mediation and moderation analysis. Multivariate regression analysis revealed that 1-hydroxynaphthalene and 2-hydroxyfluorene were negatively associated with immunoglobulin A, and 3-hydroxyphenanthrene was negatively correlated with complement component 3. Restricted cubic spline analysis demonstrated nonlinear relationships between some individual PAHs or their metabolites with immunological components. Bayesian kernel machine regression and quantile g-computation revealed significant associations of higher PAH exposure with decreased immunoglobulin G and kappa light chain levels. Phenanthrene was the compound that contributed the most to reduced immunoglobulin G. Mediation analysis demonstrated significant indirect effects of 8-hydroxydeoxyguanosine and white blood cell counts on the association between higher PAH exposure and decreased immunological components. Moderation analysis revealed that PAH exposure and decreased immunological components are significantly associated with higher levels of C-reaction protein and white blood cell counts. The results demonstrated significant immunosuppression of PAH exposure and highlighted the indirect roles of oxidative stress and inflammation. Interventions to reduce systemic inflammation may mitigate the adverse immune effects of PAH exposure.

Association of urinary 8-hydroxydeoxyguanosine level with arteriosclerosis-related factors in healthy, urban residents aged ≥50 years in Japan

Association of urinary 8-hydroxydeoxyguanosine level with arteriosclerosis-related factors in healthy, urban residents aged ≥50 years in Japan

Exposure to Benzo[a]pyrene and 1-Nitropyrene in Particulate Matter Increases Oxidative Stress in the Human Body.

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause oxidative stress in metabolic processes. This study aimed to evaluate the relationship between exposure to PAHs, including benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP), in the atmosphere and oxidative stress levels in the human body. This study included 44 Korean adults who lived in Cheongju, Republic of Korea. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene (1-OHP) concentrations were measured. The oxidative stress level was assessed by measuring urinary thiobarbituric acid-reactive substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG) concentrations. Urinary TBARS and 6-OHNP concentrations significantly differed between winter and summer. BaP exposure was significantly associated with urinary 8-OHdG concentrations in summer. However, atmospheric 1-NP did not show a significant correlation with oxidative stress marker concentrations. Urinary 1-NAAP concentration was a significant determinant for urinary 8-OHdG concentration in summer. Oxidative stress in the body increases in proportion to inhalation exposure to BaP, and more 8-OHdG is produced in the body as the amount of 1-NP, which is metabolized to 1-AP or 1-NAAP, increases.

Associations of co-exposure to polycyclic aromatic hydrocarbons and metals with hyperuricemia risk in Chinese coke oven workers: Mediating roles of oxidative damage

Ubiquitous polycyclic aromatic hydrocarbons (PAHs) and metals could induce hyperuricemia and oxidative damage individually, while their co-exposure effects on hyperuricemia risk and the potential roles of oxidative damage in these health outcomes remain poorly understood. We conducted a cross-sectional study in 1379 coke oven workers. We evaluated the levels of PAH-metal exposure and oxidative damage by urinary monohydroxy-PAHs, plasma benzo [a]pyrene-7,8-diol-9,10-epoxide-albumin (BPDE-Alb) adducts, urinary metals, urinary 8-iso-prostaglandin-F2α, and urinary 8-hydroxydeoxyguanosine (8-OH-dG). The subjects were classified into cases of hyperuricemia and controls by the levels of blood uric acid. We found that the sum of multiple hydroxyphenanthrene (ΣOH-Phe) was robustly associated with the increase in hyperuricemia risk, while rubidium and strontium had robust protective associations with hyperuricemia risk (Ptrend<0.05). The risk association of ΣOH-Phe was weaker in workers with high levels of rubidium and strontium [P for modifying effect (PME) < 0.030]. The protective association of strontium was more pronounced in workers with higher ΣOH-Phe (PME = 0.014). We also found that 8-OH-dG was a risk factor for hyperuricemia (Ptrend = 0.006) and mediated 10.13% of the elevated hyperuricemia risk associated with ΣOH-Phe. Our findings suggested that individual PAHs and metals, as well as their co-exposure, may influence hyperuricemia risk among coke oven workers, with oxidative DNA damage playing a potential mediating role in their associations.

The effects of metals and mixture exposure on lung function and the potential mediating effects of oxidative stress.

Exposure to metals is associated with lung function decline. However, limited data are available about effects of co-exposure of metals on lung function. Additionally, the mechanism of the association between metals and lung function remains unclear. We conducted a longitudinal panel study in 2017-2018 among 45 healthy college students. Urinary 15 metals, lung function, biomarkers of oxidative stress and inflammation of participants were measured. Linear mixed effect (LME) and Bayesian kernel machine regression (BKMR) models were applied to explore the associations of urinary metals and mixture with lung function. Furthermore, we analyzed the mediating effect of biomarkers in the association between urinary metals and lung function. LME models showed the negative associations of aluminum (Al), vanadium (V), manganese (Mn), cobalt (Co), nickel (Ni), cadmium (Cd) or antimony (Sb) with Forced vital capacity (FVC), and V, Co, Ni, and Sb with Forced expiratory volume in one second (FEV1). BKMR models indicated the overall effect of metals mixture was negatively associated with FEV1 and FVC; urinary Sb was identified as the major contributor to decreased FVC and FEV1. Urinary 8-hydroxydeoxyguanosine mediated the association of Al, Mn, or Sb with FVC and the relationship of V with FEV1. The results revealed the longitudinal dose-response relationships of urinary metals with pulmonary function among healthy adults. Oxidative stress may be the underlying mechanisms of metals exposure associated with decreased lung function. Due to the small sample size, the interpretation of the results of this study should be cautious, and more studies are needed to verify the findings of this study.

Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction.

Although inflammation and fibrosis, which are key mechanisms of chronic kidney disease, are associated with mitochondrial damage, little is known about the effects of mitochondrial damage on the collecting duct in renal inflammation and fibrosis. To generate collecting duct-specific mitochondrial injury mouse models, CR6-interacting factor-1 (CRIF1) flox/flox mice were bred with Hoxb7-Cre mice. We evaluated the phenotype of these mice. To evaluate the effects on unilateral ureteral obstruction (UUO)-induced renal injury, we divided the mice into the following four groups: a CRIF1flox/flox (wild-type (WT)) group, a CRIF1flox/flox-Hob7 Cre (CRIF1-KO) group, a WT-UUO group, and a CRIF1-KO UUO group. We evaluated the blood and urine chemistries, inflammatory and fibrosis markers, light microscopy, and electron microscopy of the kidneys. The inhibition of Crif1 mRNA in mIMCD cells reduced oxygen consumption and membrane potential. No significant differences in blood and urine chemistries were observed between WT and CRIF1-KO mice. In UUO mice, monocyte chemoattractant protein-1 and osteopontin expression, number of F4/80 positive cells, transforming growth factor-β and α-smooth muscle actin staining, and Masson’s trichrome staining were significantly higher in the kidneys of CRIF1-KO mice compared with the kidneys of WT mice. In sham mice, urinary 8-hydroxydeoxyguanosine (8-OHDG) was higher in CRIF1-KO mice than in WT mice. Moreover, CRIF1-KO sham mice had increased 8-OHDG-positive cell recruitment compared with WT-sham mice. CRIF1-KO-UUO kidneys had increased recruitment of 8-OHDG-positive cells compared with WT-UUO kidneys. In conclusion, collecting duct-specific mitochondrial injury increased oxidative stress. Oxidative stress associated with mitochondrial damage may aggravate UUO-induced renal injury.

Heavy metals controlling cardiovascular diseases risk factors in myocardial infarction patients in critically environmentally heavy metal-polluted steel industrial town Mandi-Gobindgarh (India).

Heavy metals (HMs) have a very significant clinical role in the pathogenesis, progression and management of cardiovascular diseases (CVDs). The prevalence of CVDs was reported to be higher in critically environmentally HM-polluted (EHMP) steel industrial town Mandi-Gobindgarh (India) for the last more than a decade. To ascertain the role of HMs in the onset of CVDs, the present study was chosen to investigate HMs content in myocardial infarction (MI) patients from EHMP steel industrial town Mandi-Gobindgarh. Total of 110 MI patients along with number- and age-matched healthy volunteers were recruited in the present investigation. The CVDs risk factors estimated in MI patients were overweight (higher body mass index), hypertension (higher systolic and diastolic blood pressures), dyslipidaemia (higher serum cholesterol, triglycerides and lower HDL cholesterol), inflammation (higher-serum C reactive protein and aldosterone) and elevated oxidative stress (higher urinary 8-hydroxydeoxyguanosine). An imbalance of serum electrolyte concentrations including Na (hypernatremia), Ca (hypercalcaemia) and K (hypokalaemia) was also observed in MI patients in which CVDs risk factors were found to correlate positively with serum Na and Ca and negatively with serum K, respectively. Hair HM analysis was used as a bio-indicator for monitoring body HM status from past environmental HM exposure in which CVDs risk factors were observed to correlate positively with higher hair concentrations of Zn, Fe, Mo, Pb, As, Ca and Na and negatively with lower hair concentrations of Cu, Mg, Mn and K in MI patients, respectively. Thus, higher hair concentrations of Zn and Pb indicate their higher environmental exposure and possible cause of higher CVDs risk factors in MI patients from Mandi-Gobindgarh.

Amelioration of lithiatic injury to renal tissue by candesartan and sodium thiosulfate in a rat model of nephrolithiasis.

AimNephrolithiasis is a chronic metabolic condition affecting 10% of population worldwide. The present study aimed to investigate the possible protective role of candesartan (CAND) and sodium thiosulfate (STS) in ameliorating ethylene glycol (EG) induced nephrolithiasis.MethodsOne hundred male Wistar rats were divided into five groups: Normal control group, nephrolithiasis (EG) group (1% EG in drinking water), Cystone (CYS) group (EG + 750 mg/kg CYS, orally, once daily), STS group (EG + 0.4 gm/kg STS, intraperitoneally, 3 times/week) and CAND group (EG + 70 μg/mL CAND in drinking water). Treatments and EG administration commenced on the same day and continued for 28 days. CYS was used as reference drug. Urine, blood, and renal tissues were collected at the end of the experiment for assessment of kidney function tests (serum creatinine and urea), urinary (8-hydroxydeoxyguanosine (8-OHdG), calcium and oxalate), inflammatory and oxdative stress biomarkers (transforming growth factor beta (TGF-β), osteopontin (OPN) and ratio of reduced glutathione to oxidized glutathione (GSH/GSSG)) in renal tissue.ResultsSerum (creatinine and urea), urinary (8-OHdG and oxalate) and renal (OPN and TGF-β) were significantly reduced in CAND and STS groups compared to EG group. Furthermore, renal GSH/GSSG and urinary calcium were significantly increased in CAND and STS groups compared to EG group. Histopathological results support the biochemical findings; CAND and STS groups showed less retention of crystals and necrotic damage in kidney. Also, microscopic examination of urine revealed less crystal for CAND and STS groups.ConclusionCandesartan and sodium thiosulfate exhibited protective effect against nephrolithiasis.

Biomarkers of Low-Level Environmental Exposure to Benzene and Oxidative DNA Damage in Primary School Children in Sardinia, Italy.

Background: The main anthropic sources of exposure to airborne benzene include vehicular traffic, cigarette smoke, and industrial emissions. Methods: To detect early genotoxic effects of environmental exposure to benzene, we monitored environmental, personal, and indoor airborne benzene in children living in an urban area and an area near a petrochemical plant. We also used urinary benzene and S-phenylmercapturic acid (S-PMA) as biomarkers of benzene exposure and urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of early genotoxic effects. Results: Although always below the European Union limit of 5 μg/m3, airborne benzene levels were more elevated in the indoor, outdoor, and personal samples from the industrial surroundings compared to the urban area (p = 0.026, p = 0.005, and p = 0.001, respectively). Children living in the surroundings of the petrochemical plant had urinary benzene values significantly higher than those from the urban area in both the morning and evening samples (p = 0.01 and p = 0.02, respectively). Results of multiple regression modelling showed that age was a significant predictor of 8-OHdG excretion, independent of the sampling hour. Moreover, at the low exposure level experienced by the children participating in this study, neither personal or indoor airborne benzene level, nor personal monitoring data, affected 8-OHdG excretion. Conclusions: Our results suggest the importance of biological monitoring of low-level environmental exposure and its relation to risk of genotoxic effects among children.

Circulating lead modifies hexavalent chromium-induced genetic damage in a chromate-exposed population: An epidemiological study

Chromium (Cr) can coexist with other heavy metals in the blood of chronically chromate-exposed individuals. However, few studies have explored the health impacts of other hazardous metals after exposure to hexavalent chromium [Cr(VI)]. This study aimed to assess the modification effects of blood lead (Pb) on the genetic damage induced by Cr(VI). During 2010–2019, 1000 blood samples were collected from 455 workers exposed to chromate and 545 workers not exposed to chromate from the same factory with similar labor intensity. The levels of Cr and Pb were measured in whole blood samples. Micronucleus frequency (MNF) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured to reflect different types of genetic damage. Multivariate linear regression analyses were performed to evaluate the associations between hazardous metals and the modification effects of Pb on genetic damage. The geometric mean levels of Cr and Pb in the exposure group were significantly higher than those in the control group [Cr: 6.42 (6.08– 6.79) vs. 1.29 (1.22– 1.36) μg/L; Pb: 38.82 (37.22– 40.50) vs. 34.47 (33.15– 35.85) μg/L]. The geometric means of urinary 8-OHdG and MNF in exposure group were 4.00 (3.64– 4.40) μg/g and 5.40 (4.89– 5.97) ‰, respectively, significantly higher than the 3.20 (2.94– 3.48) μg/g and 4.57 (4.15– 5.03) ‰, respectively, in control group. log2Cr was independently and positively associated with urinary 8-OHdG (β-adjusted = 0.143, 95% CI: 0.082– 0.204) and MNF (β-adjusted = 0.303, 95%CI: 0.020– 0.587). With the change in circulating Pb levels, the types of genetic damage induced by Cr(VI) were different. At low levels of circulating Pb (<30.80 μg/L), chromate mainly caused changes in 8-OHdG, while at high circulating Pb levels (≥44.88 μg/L), chromate induced alterations in MNF. The findings suggested that chromate exposure could cause multiple types of genetic damage, and circulating Pb might modify the association between circulating Cr and the form of genetic damage.

Clinical impact of admission urinary 8-hydroxydeoxyguanosine level for predicting cardiovascular mortality in patients with acute coronary syndrome.

The aim of the present study was to determine whether urinary 8-hydroxydeoxyguanosine (8-OHdG), which is a marker of oxidative stress, can predict future cardiovascular death in patients with acute coronary syndrome (ACS). A total of 551 consecutive patients with ACS who underwent admission urinary 8-OHdG measurements were enrolled in this study. The patients were divided into 2 groups according to the optimal cutoff value of admission urinary 8-OHdG determined by a receiver-operating characteristics curve for the prediction of cardiovascular death: a high admission urinary 8-OHdG group, 169 patients with admission urinary 8-OHdG ≥ 17.92ng/mg creatinine; and a low admission urinary 8-OHdG group, 382 patients with admission urinary 8-OHdG < 17.92ng/mg creatinine. The patients were followed up for a median period of 34months. The primary and secondary end points were the incidence of cardiovascular death and major cardiovascular events (MACE) composed of cardiovascular death, non-fatal myocardial infarction, or urgent hospitalization for heart failure. Of the 551 patients, cardiovascular deaths and MACE occurred in 14 (2.5%) and 35 (6.4%), respectively. The Kaplan-Meier estimate of the event-free rate revealed cardiovascular deaths and MACE were more likely in the high admission 8-OHdG group than in the low admission 8-OHdG group (log rank, both P < 0.001). Multiple adjusted Cox proportional hazards analysis indicated that high admission urinary 8-OHdG was an independent predictor of cardiovascular death (hazard ratio [HR] 7.642, P = 0.011) and MACE (HR 2.153, P = 0.049). High admission urinary 8-OHdG levels predict cardiovascular mortality after adjustment in patients with ACS.

Effects of Neonatal Caffeine Administration on Vessel Reactivity in Adult Mice.

The effects of neonatal caffeine therapy in adults born preterm are uncertain. We studied the impact of neonatal caffeine on systemic blood pressure, vessel reactivity, and response to stress in adult mice. Mice pups were randomized to caffeine (20 mg/kg/d) or saline by intraperitoneal injection for 10 days after birth. We performed tail-cuff BP (8/12 weeks), urinary 8-hydroxydeoxyguanosine and fecal corticosterone (14 weeks), and vessel reactivity in aortic rings (16 weeks) in adult mice. No differences were noted in systolic, diastolic, and mean blood pressures between the two groups at 8 and 12 weeks of age. However, norepinephrine-induced vasoconstriction was substantially higher in aortic rings in CAF-treated male mice. More significant vasodilator responses to nitric oxide donors in aortic rings in female mice may suggest gender-specific effects of caffeine. Female mice exposed to caffeine had significantly lower body weight over-time. Caffeine-treated male mice had substantially higher fecal corticosterone and urinary 8-hydroxydeoxyguanosine at 14 weeks, suggestive of chronic stress. We conclude sex-specific vulnerability to the heightened vascular tone of the aorta in male mice following neonatal caffeine therapy. Altered vessel reactivity and chronic stress in the presence of other risk factors may predispose to the development of systemic hypertension in adults born preterm.

1109-P: Blood Pressure (BP) Lowering Effect of Empagliflozin Is Related to Decreased L-Arginine Clearance in Diabetic Rats

Introduction: The availability of L-arginine is the rate-limiting factor in Nitric Oxide (NO) synthesis, a potent vasodilatory factor. L-arginine plasma levels are blunted in diabetes, thus L-arginine supplementation decreases BP in animal diabetic models, and type 2 diabetic patients. Renal reabsorption of filtered L-arginine in the proximal tubule is mainly sodium dependent. Higher filtered glucose load in diabetes may alter sodium gradient via higher glucose reabsorption by sodium-glucose cotransporters (SGLTs). Purpose: The mechanism by which SGLT2 inhibitors, such as Empagliflozin, decrease BP in type 2 diabetic patients, is still unknown. We hypothesize that SGLT2 inhibitors could decrease the urinary excretion of L-arginine, by restoring sodium gradient necessary for L-arginine reabsorption in the proximal tubule. Methods: Male obese Zucker diabetic fatty/Spontaneously hypertensive heart failure hybrid (ZSF1) rats and their lean littermates (CTR) received either Empagliflozin or vehicle for 6 weeks. Levels of L-arginine in urine and plasma were quantified via Liquid Chromatography-Mass Spectrometry. Plasmatic cGMP level, a marker of NO production and urinary 8-hydroxydeoxyguanosine (8-OHdG) level, a marker of oxidative stress, were measured. Results: The urinary level of L-arginine was higher in ZSF-1 rats compared to CTR ones, and plasmatic concentrations of L-arginine were lower in ZSF-1 rats compared to CTR ones. Both parameters were significantly reversed by Empagliflozin. Empagliflozin treatment increased plasmatic cGMP and decreased urinary 8-OHdG in diabetic rats. Conclusion: Empagliflozin decreased urinary excretion of L-arginine, associated with an increased plasmatic concentration of L-arginine and cGMP, and decreased oxidative stress in diabetic rats. This suggests that Empagliflozin increased NO production and bioavailability. Such effects might contribute to the BP lowering effect of Empagliflozin in diabetics. Disclosure S. Khemais-Benkhiat: Employee; Self; Boehringer Ingelheim International GmbH. D. Veyel: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. V. Schini-Kerth: Research Support; Self; Boehringer Ingelheim International GmbH. B. Krawczyk: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Pieper: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Mark: Employee; Self; Boehringer Ingelheim International GmbH. E. Mayoux: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

PD22-04 ORAL ADMINISTRATION OF NANO-SIZED SILICON PARTICLES REGULATES GENE EXPRESSION RELATED TO OXIDATIVE STRESS AND SUPPRESSES RAT RENAL ISCHEMIA-REPERFUSION INJURY

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I (PD22)1 Apr 2020PD22-04 ORAL ADMINISTRATION OF NANO-SIZED SILICON PARTICLES REGULATES GENE EXPRESSION RELATED TO OXIDATIVE STRESS AND SUPPRESSES RAT RENAL ISCHEMIA-REPERFUSION INJURY Masataka Kawamrua*, Ryoichi Imamura, Yuki Kobayashi, Ayumu Taniguchi, Shigeaki Nakazawa, Taigo Kato, Toyofumi Abe, Hikaru Kobayashi, and Norio Nonomura Masataka Kawamrua*Masataka Kawamrua* More articles by this author , Ryoichi ImamuraRyoichi Imamura More articles by this author , Yuki KobayashiYuki Kobayashi More articles by this author , Ayumu TaniguchiAyumu Taniguchi More articles by this author , Shigeaki NakazawaShigeaki Nakazawa More articles by this author , Taigo KatoTaigo Kato More articles by this author , Toyofumi AbeToyofumi Abe More articles by this author , Hikaru KobayashiHikaru Kobayashi More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000872.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Organ ischemia reperfusion injury (IRI) is unavoidable in kidney transplantation and induces reactive oxygen species and causes organ damage. Although the effectiveness of hydrogen for IRI has been reported for a long time, oral ingestion of hydrogen water and inhalation of hydrogen gas are difficult to apply widely in terms of efficiency and general use. We succeeded in generating a large amount of hydrogen by crushing silicon to nano-sized particle and reacting with water. A silicone component agent was administered to a rat model of renal IRI to examine whether renal injury could be suppressed. METHODS: Six-week-old male SD rats were administered a silicon component feed containing 1% nano-sized silicon particles and IRI surgery was performed one week later. This group was made into a silicon component group (IRI + Si group). An IRI group that administers normal diet and performs IRI surgery and a sham group that performs only right nephrectomy were prepared, and each group was compared 72 hours after surgery. RESULTS: Serum creatinine levels and urine protein significantly decreased in the IRI + Si group,compared to the IRI group. Serum malondialdehyde and urinary 8-hydroxydeoxyguanosine, which are oxidative stress markers, were also significantly decreased in the IRI + Si group. Transcriptome analysis by microarray showed that in the IRI + Si group, the expression of genes related to immune response, cytokine production, and apoptotic signal was decreased in comparison with the IRI group. Furthermore, suppression of mRNA expression level of inflammatory cytokines by quantitative PCR and reduction of renal tubular epithelial cell apoptosis by immunohistochemical evaluation were obtained, suggesting anti-inflammatory and anti-apoptotic effects. CONCLUSIONS: Rat renal IRI was suppressed by oral administration of nano-sized silicon particles, which is a novel hydrogen administration method. Source of Funding: This research was supported by Grants-in-aid for Scientific Research (18K16697) and Center of Innovation Science and Technology based Radical Innovation and Entrepreneurship Program (COI STREAM). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e460-e460 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masataka Kawamrua* More articles by this author Ryoichi Imamura More articles by this author Yuki Kobayashi More articles by this author Ayumu Taniguchi More articles by this author Shigeaki Nakazawa More articles by this author Taigo Kato More articles by this author Toyofumi Abe More articles by this author Hikaru Kobayashi More articles by this author Norio Nonomura More articles by this author Expand All Advertisement PDF downloadLoading ...

Oral Administration of Si-Based Agent Attenuates Oxidative Stress and Ischemia-Reperfusion Injury in a Rat Model: A Novel Hydrogen Administration Method.

Organ ischemia-reperfusion injury (IRI), which is unavoidable in kidney transplantation, induces the formation of reactive oxygen species and causes organ damage. Although the efficacy of molecular hydrogen (H2) in IRI has been reported, oral intake of H2-rich water and inhalation of H2 gas are still not widely used in clinical settings because of the lack of efficiency and difficulty in handling. We successfully generated large quantities of H2 molecules by crushing silicon (Si) to nano-sized Si particles (nano-Si) which were allowed to react with water. The nano-Si or relatively large-sized Si particles (large-Si) were orally administered to rats with renal IRI. Animals were divided into four groups: sham, IRI, IRI + nano-Si, and IRI + large-Si. The levels of serum creatinine and urine protein were significantly decreased 72 h following IRI in rats that were administered nano-Si. The levels of oxidative stress marker, urinary 8-hydroxydeoxyguanosine were also significantly decreased with the nano-Si treatment. Transcriptome and gene ontology enrichment analyses showed that the oral nano-Si intake downregulated the biological processes related to oxidative stress, such as immune response, cytokine production, and extrinsic apoptotic signaling pathway. Alterations in the regulation of a subset of genes in the altered pathways were validated by quantitative polymerase chain reaction. Furthermore, immunohistochemical analysis demonstrated that the nano-Si treatment alleviated interstitial macrophage infiltration and tubular apoptosis, implicating the anti-inflammatory and anti-apoptotic effects of nano-Si. In conclusion, renal IRI was attenuated by the oral administration of nano-Si, which should be considered as a novel H2 administration method.

Impact of hydrogen-rich gas mixture inhalation through nasal cannula during post-exercise recovery period on subsequent oxidative stress, muscle damage, and exercise performances in men.

Molecular hydrogen has been suggested to have a cytoprotective effect on the whole body and to enhance exercise performances. However, the effect of hydrogen-rich gas mixture (HG) inhalation on physiological responses has been poorly investigated. We examined the impact of acute HG inhalation on subsequent oxidative stress, muscle damage, and exercise performances during the recovery period after a strenuous exercise. This is a two-trial, double-blind, crossover, repeated measures study. Eight physically active male volunteers inhaled HG (estimated fraction of inspired oxygen and hydrogen were 21.57 and 4.08% at most, respectively) or normal gas (placebo, ambient air 400 m above sea level) during a 60-minute recovery phase after oxidative stress-inducing exercise) completion comprising 30-minute treadmill running at an intensity corresponding to 75% of maximal oxygen uptake and squat jumps (5 sets × 10 repetitions). Before oxidative stress-inducing exercise and 10 minutes after the post-exercise gas inhalation, blood and urine samples were obtained and exercise performances (jumping ability; pedaling power output; muscle strength) were evaluated. Post-exercise HG inhalation attenuated the increase in urinary 8-hydroxydeoxyguanosine excretion rate (P < 0.05), a DNA oxidation marker, and the reduction in the countermovement jump height (P < 0.05), compared with Placebo inhalation. Other exercise performances and blood oxidative stress and muscle damage markers did not differ between HG and Placebo inhalation. Moreover, the increase in urinary 8-hydroxydeoxyguanosine excretion rate was significantly associated with countermovement jump performance reduction (r = –0.78, P < 0.01). These findings suggested that HG inhalation during post-exercise recovery period might improve exercise performance via reducing systemic oxidative damage. The study was approved by the Human Research Ethics Committee of the University of Yamanashi (approval No. H29-006) on June 28, 2017.

Workers' Lifestyles and Urinary 8-hydroxydeoxyguanosine as an Oxidative Stress Marker

Oxidative stress in biological components has become recognized as one of the causative factors of various diseases. In this study, we investigated the effects of worker lifestyle and fatigue on the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress. Our results revealed that urinary 8-OHdG level was increased by alcohol intake and decreased by snack intake and adequate sleep time on the day before the survey. A decrease in urinary 8-OHdG level was also observed in parallel with a decrease in workload. Urinary 8-OHdG monitoring is expected to be useful for disease prevention in the future.

Abstract 219: Supplement Oxygen Dependence of Dissociated Oxygen Metabolism From Carbon Dioxide and Oxidative Toxic Stress in Post-Cardiac Arrest

Objective: We recently reported a dissociation of oxygen metabolism in post-cardiac arrest rodents, which was represented by an increase in oxygen consumption (VO 2 ) without a concomitant increase in carbon dioxide generation (VCO 2 ) resulting in a lowered respiratory quotient (RQ) outside of the normally cited range of 0.7-1.0. We hypothesize that high supplemental O 2 is associated with both increased dissociation of oxygen metabolism and oxidative toxic stress after cardiac arrest (CA). Methods: Rats were resuscitated from 10 minutes of asphyxial CA and stratified into 2 groups: those that inhaled 100% supplemental O 2 (CA-FIO2 1.0) and those that inhaled 30% supplemental O 2 (CA-FIO2 0.3). We prepared a sham surgery group for comparison (sham-FIO2 0.3). Our newly developed method enabled measurements of VO 2 and VCO 2 from low to high inspiratory supplemental O 2 levels. RQ was calculated as VCO 2 /VO 2 . After 2 hours, we collected urine and tissue samples to determine the degree of reactive oxygen species (ROS) generation. Results: CA increased VO 2 (28.5±8.1 mL/kg/min at FIO2 1.0 and 19.1±3.0 at FIO2 0.3, p&lt;0.05) compared with the sham group (15.0±1.4), whereas no differences in VCO 2 were found among the three groups. RQ of CA-FIO2 1.0 animals persistently decreased to 0.57±0.03 (0.84 ±0.10 at CA-FIO2 0.3 and 0.96±0.14 at sham-FIO2 0.3). Regarding ROS generation, urinary 8-hydroxydeoxyguanosine (8-OHdG) and brain carbonyl protein of CA-FIO2 1.0 animals was significantly higher than the CA-FIO2 0.3 or sham groups. Conclusions: 100% supplemental oxygen increased VO 2 but not VCO 2 . 8-OHdG is produced during the repair of cellular DNA damaged from oxidative toxic stress and excreted into the urine. Our findings suggest that the high supplemental oxygen aggravate both dissociation of oxygen metabolism and oxidative toxic stress in post-CA rodents.

Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients

Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as New York Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients.