Effects of everolimus on oxidative stress in kidney model of ischemia/reperfusion injury
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Effects of everolimus on oxidative stress in kidney model of ischemia/reperfusion injury. / Kezic, Aleksandra; Thaiss, Friedrich; Becker, Jan U; Tsui, Tung Y; Bajcetic, Milica.
In: AM J NEPHROL, Vol. 37, No. 4, 01.01.2013, p. 291-301.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Effects of everolimus on oxidative stress in kidney model of ischemia/reperfusion injury
AU - Kezic, Aleksandra
AU - Thaiss, Friedrich
AU - Becker, Jan U
AU - Tsui, Tung Y
AU - Bajcetic, Milica
N1 - Copyright © 2013 S. Karger AG, Basel.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - BACKGROUND/AIMS: Reactive oxygen species play an important role in the pathogenesis of kidney ischemia/reperfusion injury (IRI) which may be influenced by immunosuppressive therapy. Pertinent to this, we investigated the effects of the mTOR inhibitor everolimus on redox settings and the activity of the anti-oxidative system in kidneys exposed to IRI.METHODS: C57BL/6 mice were subjected to IRI by clamping both renal pedicles for 45 min. Everolimus was applied in daily, subcutaneous doses (0.25 mg/kg body weight), starting 1 day before IRI induction. Both everolimus-treated and non-treated mice were sacrificed at several time points, starting 30 min and finishing 7 days after IRI induction. Markers of oxidation such as glutathione and NADPH levels and anti-oxidative enzyme activities were determined in the kidneys.RESULTS: In comparison to both sham and non-treated animals, the treatment with everolimus resulted in an increased level of markers of oxidation, including a lower level of glutathione, increased level of oxidized glutathione and reduced level of NADPH. The activity of superoxide dismutase was reduced in both experimental groups, but the effects were less pronounced in everolimus-treated animals. In the early phase of reperfusion, everolimus-treated animals showed higher activity of glutathione reductase in comparison to non-treated animals, whereas the activities of glutathione peroxidase and catalase were generally similar. The treatment with everolimus significantly reduced heme oxygenase-1 expression and increased iNOS mRNA expression when compared to non-treated animals.CONCLUSION: Our data imply that everolimus treatment may decrease cytoprotective capacity in kidneys exposed to IRI due to promoted oxidative/nitrosative stress.
AB - BACKGROUND/AIMS: Reactive oxygen species play an important role in the pathogenesis of kidney ischemia/reperfusion injury (IRI) which may be influenced by immunosuppressive therapy. Pertinent to this, we investigated the effects of the mTOR inhibitor everolimus on redox settings and the activity of the anti-oxidative system in kidneys exposed to IRI.METHODS: C57BL/6 mice were subjected to IRI by clamping both renal pedicles for 45 min. Everolimus was applied in daily, subcutaneous doses (0.25 mg/kg body weight), starting 1 day before IRI induction. Both everolimus-treated and non-treated mice were sacrificed at several time points, starting 30 min and finishing 7 days after IRI induction. Markers of oxidation such as glutathione and NADPH levels and anti-oxidative enzyme activities were determined in the kidneys.RESULTS: In comparison to both sham and non-treated animals, the treatment with everolimus resulted in an increased level of markers of oxidation, including a lower level of glutathione, increased level of oxidized glutathione and reduced level of NADPH. The activity of superoxide dismutase was reduced in both experimental groups, but the effects were less pronounced in everolimus-treated animals. In the early phase of reperfusion, everolimus-treated animals showed higher activity of glutathione reductase in comparison to non-treated animals, whereas the activities of glutathione peroxidase and catalase were generally similar. The treatment with everolimus significantly reduced heme oxygenase-1 expression and increased iNOS mRNA expression when compared to non-treated animals.CONCLUSION: Our data imply that everolimus treatment may decrease cytoprotective capacity in kidneys exposed to IRI due to promoted oxidative/nitrosative stress.
KW - Animals
KW - Catalase
KW - Glutathione
KW - Glutathione Disulfide
KW - Glutathione Peroxidase
KW - Immunosuppressive Agents
KW - Kidney
KW - Mice
KW - Mice, Inbred C57BL
KW - NADP
KW - Oxidative Stress
KW - Reperfusion Injury
KW - Sirolimus
KW - Superoxide Dismutase
U2 - 10.1159/000348496
DO - 10.1159/000348496
M3 - SCORING: Journal article
C2 - 23548777
VL - 37
SP - 291
EP - 301
JO - AM J NEPHROL
JF - AM J NEPHROL
SN - 0250-8095
IS - 4
ER -