[PPAR gamma agonist rosiglitazone alleviates hypoxia/reoxygenation-induced oxidative stress and apoptosis in rat cardiac myocytes].
OBJECTIVE
To observe the effects of different concentrations of PPAR gamma agonist rosiglitazone on hypoxia/reoxygenation-induced oxidative stress, cell viability and apoptosis in rat cardiac myocytes.


METHODS
Cultured rat cardiac myocytes were divided into 5 groups, namely group I (normal group), group II (20 micromo/L ROS group), group III (I/R group), group IV (I/R+20 micromo/L ROS group), and group V (I/R+80 micromo/L ROS group). Group IV and group V were treated with rosiglitazone 12 h before hypoxia/reoxygenation. The changes in cell morphology were observed under optical and transmission electron microscopy, and levels of malondialdehyde (MDA), superoxide dismutase (SOD) activity, and lactate dehydrogenase (LDH) content were determined after the treatment. MTT assay was performed to assess the cell viability and flow cytometry was used to analyze the cell apoptosis.


RESULTS
Hypoxia/reoxygenation resulted in significantly increased MDA and LDH contents and apoptosis of the cardiac myocytes (P<0.05), but lowered SOD activity and the cell viability (P<0.05). The MDA and LDH contents and apoptotic rate were significantly lower but SOD content and cell vitality significantly higher in groups IV and V than in group III (P<0.05). Group V showed significantly lower MDA and LDH contents and apoptotic rate but higher but SOD content and cell vitality than group IV (P<0.05). Electron microscopy revealed obvious apoptotic changes in group III, and only mild changes were found in group V.


CONCLUSIONS
Rosiglitazone can significantly reduce hypoxia/reoxygenation-induced oxidative stress in cardiac myocytes, improve the cell viability and dose-dependently reduce the apoptotic rate of the cardiac myocytes.
Yao
You-jie
YJ
Department of Cardiology, Second Affiliated Hospital of Sun Yat-sen University, Guangzhou 510120, China. yaoyoujie @126.com
Geng
Deng-feng
DF
Wang
Jing-feng
JF
Yang
Min-hua
MH
Zhang
Yu-ling
YL
Nie
Ru-qiong
RQ
Zhou
Shu-xian
SX
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D013482:Superoxide Dismutase / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D010100:Oxygen