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Resveratrol reduces cardiac NLRP3‐inflammasome activation and systemic inflammation to lessen doxorubicin‐induced cardiotoxicity in juvenile mice
Author(s) -
Maayah Zaid H.,
Alam Abrar S.,
Takahara Shingo,
Soni Shubham,
Ferdaoussi Mourad,
Matsumura Nobutoshi,
Zordoky Beshay N.,
Eisenstat David D.,
Dyck Jason R.B.
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14091
Subject(s) - cardiotoxicity , doxorubicin , medicine , cardiomyopathy , inflammation , resveratrol , systemic inflammation , inflammasome , pharmacology , juvenile , heart failure , chemotherapy , biology , genetics
Doxorubicin (DOX) is a very effective anticancer agent that is widely used in pediatric cancer patients. Nevertheless, DOX is known to have cardiotoxic effects that may progress to cardiomyopathy later in life. We have recently shown that cotreatment of resveratrol (RES) with DOX in juvenile mice attenuates late‐onset hypertension‐induced cardiomyopathy. However, the molecular mechanism responsible for these changes remains unknown. Herein, we show that the cardiac NLRP3 inflammasome plays a crucial role in regulating cardiac injury in a DOX ‐treated juvenile mouse model and the detrimental effects of hypertension in these mice later in life. We further demonstrate that RES significantly reduces systemic inflammation to contribute to the improvements observed in DOX ‐induced cardiac injury in young mice and late‐onset hypertension‐induced cardiomyopathy.