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Free-radical scavenger edaravone inhibits both formation and development of abdominal aortic aneurysm in rats  Keisuke Morimoto, MD, Tomomi Hasegawa,

Published byΕυτέρπη Μητσοτάκης Modified over 6 years ago

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Presentation on theme: "Free-radical scavenger edaravone inhibits both formation and development of abdominal aortic aneurysm in rats  Keisuke Morimoto, MD, Tomomi Hasegawa,"— Presentation transcript:

1 Free-radical scavenger edaravone inhibits both formation and development of abdominal aortic aneurysm in rats  Keisuke Morimoto, MD, Tomomi Hasegawa, MD, PhD, Akiko Tanaka, MD, Bao Wulan, MD, Jie Yu, MD, Naoto Morimoto, MD, PhD, Yutaka Okita, MD, PhD, Kenji Okada, MD, PhD  Journal of Vascular Surgery  Volume 55, Issue 6, Pages (June 2012) DOI: /j.jvs Copyright © 2012 Society for Vascular Surgery Terms and Conditions

2 Fig 1 Edaravone or saline was intraperitoneally injected twice a day, starting 30 minutes before aneurysm preparation. Rats in the low-dose group (Group LD) received 1 mg/kg/d edaravone, rats in the high-dose group (Group HD) received 5 mg/kg/d edaravone, and control rats (Group C) received saline. Rats in the delayed administration group (Group DA) received 5 mg/kg/d edaravone starting at 7 days after aneurysm preparation to 28 days. PCR, Polymerase chain reaction; ROS, reactive oxygen species. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

3 Fig 2 The panels show aneurysm formation of the abdominal aorta at 28 days in each group. Control rats (Group C) received saline administration; the low-dose rats (Group LD) received 1 mg/kg/d edaravone, and the high-dose rats (Group HD) received 5 mg/kg/d edaravone. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

4 Fig 3 Histologic findings of abdominal aortic aneurysm at day 28 stained with (A) hematoxylin and eosin for the assessment of aortic wall thickness and (B) elastica van Giesen for the assessment of elastin content. The upper panels are at original magnification, ×40 (bar = 300 μm), and the lower panels are at original magnification, ×400 (bar = 100 μm). C, Quantitative analysis of aortic wall thickness and elastin content is shown as mean ± standard deviation (error bars) for six rats per group. Statistical analysis was by one-way analysis of variance with post hoc Games-Howell test. *P < .05, **P < .01 vs group C, †P < 0.01 vs the LD group. Native, Normal rats; Group C, rats received saline administration as a control; Group LD, rats received low-dose edaravone (1 mg/kg/d); Group HD, rats received high-dose edaravone (5 mg/kg/d). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

5 Fig 4 Reactive oxygen species production in aneurysm walls at day 7. A, In situ detection of superoxide by dihydroethidium stain is shown (upper panels, original magnification, ×40; lower panels, original magnification, ×400). B, The mean fluorescence in high-power field was quantified and expressed as values for native rat; with all data are expressed as mean ± standard deviation (error bars) for six rats per group. Statistical analysis was done with one-way analysis of variance with post hoc Games-Howell test. *P < .01 vs all other groups. Native, Normal rats; Group C, rats received saline administration as a control; Group LD, rats received low-dose edaravone (1 mg/kg/d); Group HD, rats received high-dose edaravone (5 mg/kg/d). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

6 Fig 5 A, Immunostaining of 8-hydroxydeoxyguanosine (8-OHdG)-positive cells in aneurysm walls at day 7 are shown (original magnification, ×400). B, The number of 8-OHdG–positive cells was counted in the high-power field. All data are expressed as mean ± standard deviation (error bars) for six rats per group. Statistical analysis was done using one-way analysis of variance with post hoc Games-Howell test. *P < .001 vs all other groups. Native, Normal rats; Group C, rats received saline administration as a control; Group LD, rats received low-dose edaravone (1 mg/kg/d); Group HD, rats received high-dose edaravone (5 mg/kg/d). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

7 Fig 6 A, Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assays in aneurysm walls at day 7 are shown (original magnification, ×400). B, The number of TUNEL-positive cells was counted in the high-power field. All data are expressed as mean ± standard deviation (error bars) for six rats per group. Statistical analysis was done with one-way analysis of variance with post hoc Games-Howell test. *P < .001 vs group C, †P < 0.01 vs group LD. Native, Normal rats; Group C, rats received saline administration as a control; Group LD, rats received low-dose edaravone (1 mg/kg/d); Group HD, rats received high-dose edaravone (5 mg/kg/d). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

8 Fig 7 A, Immunostaining of CD3-positive cells in aneurysm walls at day 7 are shown (original magnification, ×400). B, The number of CD3-positive cells was counted in the high-power field. All data are expressed as mean ± standard deviation (error bars) for six rats per group. Statistical analysis was done using one-way analysis of variance with post hoc Games-Howell test. *P < .001 vs all other groups. Native, Normal rats; Group C, rats received saline administration as a control; Group LD, rats received low-dose edaravone (1 mg/kg/d); Group HD, rats received high-dose edaravone (5 mg/kg/d). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

9 Fig 8 Intra-aortic messenger RNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, matrix metalloproteinase (MMP)-2, and MMP-9 in the aneurysm wall at day 7. All data are expressed as mean ± standard deviation (error bars) for six rats per group. Statistical analysis was done using one-way analysis of variance with post hoc Games-Howell test. *P < .01, **P < .05 vs group C, †P < 0.01 vs group LD. Group C, Rats received saline administration as a control; Group LD, rats received low-dose edaravone (1 mg/kg/d); Group HD, rats received high-dose edaravone (5 mg/kg/d). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

10 Fig 9 Effect of delayed administration of edaravone. All data are expressed as mean ± standard deviation (error bars) for six rats per group. A, Aortic dilatation ratio (%). B, Aortic wall thickness and elastin content at day 28. Group C, Rats received saline administration as a control; Group DA, rats received delayed administration of edaravone (5 mg/kg/d) starting at day 7. *P < .001 vs group C. NS, Not significant. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

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