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Thymoquinone protects against myocardial ischemia‐reperfusion injury via modulation of oxidant generation and nuclear factor‐kappaB‐mediated responses (1080.1)
Author(s) -
ElMahdy Mohamed,
Ismail Raed,
Hemann Craig,
ElSherbiny Gamal,
Abdelghany Tamer,
Helal Gouda,
Zweier Jay
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1080.1
Subject(s) - thymoquinone , reperfusion injury , ischemia , pharmacology , medicine , p38 mitogen activated protein kinases , reactive oxygen species , apoptosis , ligation , mapk/erk pathway , chemistry , cardiology , kinase , antioxidant , biochemistry
Understanding the mechanisms of natural compounds in modulating disease has moved to the forefront of cardiovascular research. Thymoquinone (TQ), a constituent of the volatile oil derived from Nigella sativa seeds, has demonstrated promising effects against ischemia‐reperfusion (IR) injury of different organs; however, the mechanism of TQ action on myocardial IR injury (m‐IRI) warrants more investigation. Rat hearts were either subjected to 30 min of global ischemia followed by 120 min of reperfusion using a Langendorff system, or to 30 min of left anterior descending coronary artery (LAD) ligation followed by 24h of reperfusion. TQ was infused ex‐vivo for 10 min either pre‐or post‐ischemia or IP‐injected for seven days prior to the surgery. TQ significantly reduced reactive oxygen species (ROS) generation, infarct size and apoptosis, and markedly enhanced coronary flow and ventricular function of the ischemic hearts. TQ attenuated the IR‐induced up‐regulation of SAPK/JNK, myocardial nuclear factor (NF)‐kappaB, TNF‐α, and P38‐MAPK expression and increased the Bcl‐2/Bax ratio. The data indicate that TQ inhibited ROS generation‐induced NF‐kappaB which led to inhibition of pro‐inflammatory cytokines and apoptosis, protecting the heart against IR injury. This study presents a new molecular mechanism of action and efficacy of TQ with promise as a natural compound in the management of m‐IRI. Grant Funding Source : NIH# 784 & Egyptian Government