- Email: [email protected]
Nox4 provides renoprotection in contrast induced nephropathy
S46
E. Chiaradia et al. / Free Radical Biology and Medicine 96 (2016) S32–S69
Results: Total oxidant status levels were significantly higher in Group DIR, when compared with Groups C, DP, and DIRP (p ¼ .001, p ¼.019, and p ¼ .031, respectively). Total antioxidant status levels were significantly higher in Group DIR, when compared with groups C, DP, and DIRP (p ¼ .006, p ¼ .024, and p ¼ .007, respectively). Conclusion: These results indicate that administration of picroside II may have protective effects against I/R injury. http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.094 P-32
Oxidative stress in brain during fetal-to-neonatal transition under an hypoxic atmosphere Maria Isabel Torres-Cuevas 1, J. Escobar 1, E. Cubells 1, R. Rodrigo 2, M. Vento 1,3 1
Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain 2 Division of Genetics, University and Polytechnic Hospital La Fe, CIBERER, Valencia, Spain 3 Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain
Background: Newborn asphyxia is one of the main complications during the perinatal period. The use of Oxygen for resuscitation has been broadly used in clinic for many years. However, it has been demonstrated that oxygen overexposure induces an oxidative stress (OS). Hypothesis: We speculate that delaying postnatal in the extrauterine oxygenation status would preserve reducing equivalents, enhance redox adaptation, and protect oxyregulator tissues (e.g.:brain). Objective: To assess oxidative stress and inflammation status, induced by Fetal to Neonatal Transition (FNT) under different FiO2 conditions, in brain of mice pups. Material and Methods: FiO2 in pregnant mice was reduced from 21% (room air) to 14% (Hx14) or not (Nx21) the night before of delivery (G18). 8 hours after birth both group were led to room air (Hx14/21 and Nx21/21 groups) or subjected to hyperoxia (FiO2 ¼100%) (Hx14/ 100 and Nx21/100 groups) and reset to 21% after 1 hour. At day 1 of life (P1) the pups were sacrificed and the brain tissues were snap frozen and kept at -80°C until the analysis. We set up a Mass Spectrometry (MS) method of four selected biomarkers: i) meta-tyrosine (m-tyr)/Phenylalanine (Phe), ii) orto-tyrosine (o-tyr)/Phe, iii) 3NO2tyrosine (3NO2-tyr)/para-tyrosine (tyr) and iv) 3Chloro-tyrosine (3Cltyr)/tyr ratios, to study cerebral OS and inflammation. Results: Hypoxia promotes significant changes in none of biomarkers. By contrast hyperoxia induces significant increases in m-tyr/phe and 3Cl-tyr/p-tyr. Remarkably, pre-conditioning hypoxia abrogates the rise of m-tyr/phe and 3Cl-tyr/p-tyr induced by hyperoxia as well as a decrease in the o-tyr/phe. Conclusions: Our results support the idea that FNT under hypoxic conditions could be protective to face a possible event of newborn resuscitation. http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.095
P-33
Pharmacologic inhibition provides renoprotection nephropathy
of NADPH oxidase/Nox4 in contrast induced
Bo-Young Jeong 1, Hoi Young Lee 1, Doo-ri Choi 2, Seung-Yun Han 2, Moon Hyang Park 3, Kyung-Ho Lee 4, Dong-Il Kim 4, Won-Min Hwang 4, Sung-Ro Yun 4, Se-Hee Yoon 4 1
Pharmacology, Konyang University, Daejeon, Korea Anatomy, Konyang University, Daejeon, Korea 3 Pathology, Konyang University, Daejeon, Korea 4 Internal Medicine, Konyang University, Daejeon, Korea 2
Contrast media (CM) induced nephropathy (CIN) is an acute deterioration of renal function following administration of CM in the absence of any other known reason. CIN remains a leading cause of iatrogenic acute kidney injury (AKI), despite adherence to protocols of risk assessment and prevention strategies. CIN may occur, in part, as a result of intrarenal oxidative stress. NADPH oxidases are important sources of reactive oxygen species (ROS). Among various types of NADPH oxidases, Nox4 is expressed predominantly in rodent kidney. Aims: The aim of the present study was to assess the effect of Nox4 inhibition on the prevention of CIN. To determine the role of Nox4 in CIN, the current study used GKT 137831, a recently described pyrazolopyridinedione derivative that inhibits Nox4 and Nox1. Results: The expression of Nox4 in HK-2 cells significantly increased by iohexol exposure. Pretreatment of GKT137831(most specific Nox1/4 inhibitor) resulted in reduced production of ROS, down regulation of proinflammatory marker (p38), that are implicated in CIN, and increased cellular survival in iohexol exposed HK-2 cells. Silencing of the Nox4 gene replicated theses effects by down regulation of proinflammatory markers. In CIN mice model, pretreatment with GKT137831 resulted in an attenuated vacuolar degeneration, tubular epithelial cell shedding, cellular cast formation and tubular dilatation. Collectively, these results identify Nox4 as a key source of ROS responsible for kidney injury in CIN and provide proof of principle for an innovative small molecule approach to prevent contrast induced nephropathy. http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.096 P-34
Paraoxonase activity in children with suspected mitochondrial disease Muscurel Corina 1, Elena Laura Gaman 1, Torac Elena 1, Tarta-Arsene Oana 1, Iosif Liviu 2, Gilca Marilena 1, Cristea Bogdan 1, Stroica Laura 1, Petran Madalina 1, Atanasiu Valeriu 1, Stoian Irina 1 1
Biochemistry Department, University of Medicine and Pharmacy "Carol Davila ", Bucharest, Romania 2 R&D Irist Labmed, Bucharest, Romania
E. Chiaradia et al. / Free Radical Biology and Medicine 96 (2016) S32–S69
Results: Total oxidant status levels were significantly higher in Group DIR, when compared with Groups C, DP, and DIRP (p ¼ .001, p ¼.019, and p ¼ .031, respectively). Total antioxidant status levels were significantly higher in Group DIR, when compared with groups C, DP, and DIRP (p ¼ .006, p ¼ .024, and p ¼ .007, respectively). Conclusion: These results indicate that administration of picroside II may have protective effects against I/R injury. http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.094 P-32
Oxidative stress in brain during fetal-to-neonatal transition under an hypoxic atmosphere Maria Isabel Torres-Cuevas 1, J. Escobar 1, E. Cubells 1, R. Rodrigo 2, M. Vento 1,3 1
Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain 2 Division of Genetics, University and Polytechnic Hospital La Fe, CIBERER, Valencia, Spain 3 Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain
Background: Newborn asphyxia is one of the main complications during the perinatal period. The use of Oxygen for resuscitation has been broadly used in clinic for many years. However, it has been demonstrated that oxygen overexposure induces an oxidative stress (OS). Hypothesis: We speculate that delaying postnatal in the extrauterine oxygenation status would preserve reducing equivalents, enhance redox adaptation, and protect oxyregulator tissues (e.g.:brain). Objective: To assess oxidative stress and inflammation status, induced by Fetal to Neonatal Transition (FNT) under different FiO2 conditions, in brain of mice pups. Material and Methods: FiO2 in pregnant mice was reduced from 21% (room air) to 14% (Hx14) or not (Nx21) the night before of delivery (G18). 8 hours after birth both group were led to room air (Hx14/21 and Nx21/21 groups) or subjected to hyperoxia (FiO2 ¼100%) (Hx14/ 100 and Nx21/100 groups) and reset to 21% after 1 hour. At day 1 of life (P1) the pups were sacrificed and the brain tissues were snap frozen and kept at -80°C until the analysis. We set up a Mass Spectrometry (MS) method of four selected biomarkers: i) meta-tyrosine (m-tyr)/Phenylalanine (Phe), ii) orto-tyrosine (o-tyr)/Phe, iii) 3NO2tyrosine (3NO2-tyr)/para-tyrosine (tyr) and iv) 3Chloro-tyrosine (3Cltyr)/tyr ratios, to study cerebral OS and inflammation. Results: Hypoxia promotes significant changes in none of biomarkers. By contrast hyperoxia induces significant increases in m-tyr/phe and 3Cl-tyr/p-tyr. Remarkably, pre-conditioning hypoxia abrogates the rise of m-tyr/phe and 3Cl-tyr/p-tyr induced by hyperoxia as well as a decrease in the o-tyr/phe. Conclusions: Our results support the idea that FNT under hypoxic conditions could be protective to face a possible event of newborn resuscitation. http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.095
P-33
Pharmacologic inhibition provides renoprotection nephropathy
of NADPH oxidase/Nox4 in contrast induced
Bo-Young Jeong 1, Hoi Young Lee 1, Doo-ri Choi 2, Seung-Yun Han 2, Moon Hyang Park 3, Kyung-Ho Lee 4, Dong-Il Kim 4, Won-Min Hwang 4, Sung-Ro Yun 4, Se-Hee Yoon 4 1
Pharmacology, Konyang University, Daejeon, Korea Anatomy, Konyang University, Daejeon, Korea 3 Pathology, Konyang University, Daejeon, Korea 4 Internal Medicine, Konyang University, Daejeon, Korea 2
Contrast media (CM) induced nephropathy (CIN) is an acute deterioration of renal function following administration of CM in the absence of any other known reason. CIN remains a leading cause of iatrogenic acute kidney injury (AKI), despite adherence to protocols of risk assessment and prevention strategies. CIN may occur, in part, as a result of intrarenal oxidative stress. NADPH oxidases are important sources of reactive oxygen species (ROS). Among various types of NADPH oxidases, Nox4 is expressed predominantly in rodent kidney. Aims: The aim of the present study was to assess the effect of Nox4 inhibition on the prevention of CIN. To determine the role of Nox4 in CIN, the current study used GKT 137831, a recently described pyrazolopyridinedione derivative that inhibits Nox4 and Nox1. Results: The expression of Nox4 in HK-2 cells significantly increased by iohexol exposure. Pretreatment of GKT137831(most specific Nox1/4 inhibitor) resulted in reduced production of ROS, down regulation of proinflammatory marker (p38), that are implicated in CIN, and increased cellular survival in iohexol exposed HK-2 cells. Silencing of the Nox4 gene replicated theses effects by down regulation of proinflammatory markers. In CIN mice model, pretreatment with GKT137831 resulted in an attenuated vacuolar degeneration, tubular epithelial cell shedding, cellular cast formation and tubular dilatation. Collectively, these results identify Nox4 as a key source of ROS responsible for kidney injury in CIN and provide proof of principle for an innovative small molecule approach to prevent contrast induced nephropathy. http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.096 P-34
Paraoxonase activity in children with suspected mitochondrial disease Muscurel Corina 1, Elena Laura Gaman 1, Torac Elena 1, Tarta-Arsene Oana 1, Iosif Liviu 2, Gilca Marilena 1, Cristea Bogdan 1, Stroica Laura 1, Petran Madalina 1, Atanasiu Valeriu 1, Stoian Irina 1 1
Biochemistry Department, University of Medicine and Pharmacy "Carol Davila ", Bucharest, Romania 2 R&D Irist Labmed, Bucharest, Romania