TY - JOUR
T1 - Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats
AU - Chiang, Bing Juin
AU - Chen, Tien Wen
AU - Chung, Shiu Dong
AU - Lee, Way Zen
AU - Chien, Chiang Ting
N1 - Funding Information:
This work was supported by the National Science Council of the Republic of China (NSC99-2314-B418-002-MY3 and NSC99-2628-B-002-058-MY3), Cardinal Tien Hospital (CTH105A-218), and research fund from Far-Eastern Memorial Hospital (FEMH-99-D-006).
Funding Information:
We thank National Taiwan Normal University and Cardinal Tien Hospital for equal contribution of funding and technical supports in majority. This work was supported by the National Science Council of the Republic of China (NSC99-2314-B418-002-MY3 and NSC99-2628-B-002-058-MY3), Cardinal Tien Hospital (CTH105A-218), and research fund from Far-Eastern Memorial Hospital (FEMH-99-D-006)
Publisher Copyright:
© Chiang et al.
PY - 2017
Y1 - 2017
N2 - Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Transcystometrograms were performed in urethane-anesthetized rats. The in vitro and in vivo reactive oxygen species levels and pathological changes in formalin-fixed bladder sections were evaluated. Western blotting and immunohistochemistry elucidated the pathophysiological mechanisms of oxidative stress-induced apoptosis, autophagy, and pyroptosis. P-phenylenediamine increased voiding frequency, blood and urinary bladder levels of reactive oxygen species, and neutrophil and mast cell infiltration. It also upregulated biomarkers of autophagy (LC3 II), apoptosis (poly (ADP-ribose) polymerase), and pyroptosis (Caspase 1). WCT003 and WCT006 ameliorated reactive oxygen species production, inflammation, apoptosis, autophagy, pyroptosis, and bladder hyperactivity. P-phenylenediamine increased oxidative stress, inflammatory leukocytosis, autophagy, apoptosis, and pyroptosis formation within the urinary bladder. Novel synthetic nickel-containing superoxide dismutase mimics relieved p-phenylenediamine-induced bladder inflammation and voiding dysfunction.
AB - Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Transcystometrograms were performed in urethane-anesthetized rats. The in vitro and in vivo reactive oxygen species levels and pathological changes in formalin-fixed bladder sections were evaluated. Western blotting and immunohistochemistry elucidated the pathophysiological mechanisms of oxidative stress-induced apoptosis, autophagy, and pyroptosis. P-phenylenediamine increased voiding frequency, blood and urinary bladder levels of reactive oxygen species, and neutrophil and mast cell infiltration. It also upregulated biomarkers of autophagy (LC3 II), apoptosis (poly (ADP-ribose) polymerase), and pyroptosis (Caspase 1). WCT003 and WCT006 ameliorated reactive oxygen species production, inflammation, apoptosis, autophagy, pyroptosis, and bladder hyperactivity. P-phenylenediamine increased oxidative stress, inflammatory leukocytosis, autophagy, apoptosis, and pyroptosis formation within the urinary bladder. Novel synthetic nickel-containing superoxide dismutase mimics relieved p-phenylenediamine-induced bladder inflammation and voiding dysfunction.
KW - Micturition
KW - Ni-SOD mimics
KW - Para-phenylenediamine
KW - Programmed cell death
KW - Urinary bladder
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U2 - 10.18632/oncotarget.22395
DO - 10.18632/oncotarget.22395
M3 - Article
C2 - 29285288
AN - SCOPUS:85036500270
SN - 1949-2553
VL - 8
SP - 105735
EP - 105748
JO - Oncotarget
JF - Oncotarget
IS - 62
ER -