Allopurinol Protects against Ischemia/Reperfusion-Induced Injury in Rat Urinary Bladders.
Bladder ischemia-reperfusion (I/R) injury results in the generation of reactive oxygen species (ROS) and markedly elevates the risk of lower urinary tract symptoms (LUTS). Allopurinol is an inhibitor of xanthine oxidase (XO) and thus can serve as an antioxidant that reduces oxidative stress. Here, a rat model was used to assess the ability of allopurinol treatment to ameliorate the deleterious effects of urinary bladder I/R injury. I/R injury reduced the in vitro contractile responses of longitudinal bladder strips, elevated XO activity in the plasma and bladder tissue, increased the bladder levels of tumor necrosis factor-α (TNF-α), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase, reduced the bladder levels of extracellular regulated kinase (ERK), and decreased and increased the bladder levels of Bcl-2 and Bax, respectively. I/R injury also elevated lipid peroxidation in the bladder. Allopurinol treatment in the I/R injury was generated significantly ameliorating all I/R-induced changes. Moreover, an in situ fluorohistological approach also showed that allopurinol reduces the generation of intracellular superoxides enlarged by I/R injury. Together, the beneficial effects of allopurinol reducing ROS production may be mediated by normalizing the activity of the ERK, JNK, and Bax/Bcl-2 pathways and by controlling TNF-α expression.
Department of Urology, School of Medicine, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
Ju-Hyun
JH
Shin
Department of Surgery, School of Medicine, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
Kwang Sik
KS
Chun
Department of Urology, School of Medicine, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
Yong-Gil
YG
Na
Department of Urology, School of Medicine, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
Ki-Hak
KH
Song
Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Daejeon 305-333, Republic of Korea.
Seung Il
SI
Kim
Department of Urology, School of Medicine, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
Jae-Sung
JS
Lim
Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Daejeon 305-333, Republic of Korea ; Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea.
Gun-Hwa
GH
Kim
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D000493:Allopurinol; D014969:Xanthine Oxidase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases