Resveratrol reduces cardiac NLRP3-inflammasome activation and systemic inflammation to lessen doxorubicin-induced cardiotoxicity in juvenile mice

Zaid H. Maayah, Abrar S. Alam, Shingo Takahara, Shubham Soni, Mourad Ferdaoussi, Nobutoshi Matsumura, Beshay N. Zordoky, David D. Eisenstat, Jason R.B. Dyck

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1681-1695
Number of pages15
JournalFEBS Letters
Volume595
Issue number12
DOIs
StatePublished - Jun 2021

Bibliographical note

Funding Information:
This work was supported by a grant from the Canadian Institutes of Health Research (CIHR) to JRBD and a grant from the Women and Children’s Health Research Institute (WCHRI) Hair Massacure Fund, University of Alberta to JRBD and DDE. JRBD is a Canada Research Chair in Molecular Medicine. ZHM is the recipient of the Alberta Innovates Health Solutions and CIHR postdoctoral fellowship awards. DDE holds the Muriel & Ada Hole Kids with Cancer Society Chair in Pediatric Oncology, University of Alberta. BNZ is supported by the National Heart, Lung, and Blood Institute grant R01HL151740 and the National Institutes of Health’s National Center for Advancing Translational Sciences grant UL1TR002494. SS is supported by Graduate Student Scholarships from WCHRI and Alberta Innovates.

Funding Information:
This work was supported by a grant from the Canadian Institutes of Health Research (CIHR) to JRBD and a grant from the Women and Children?s Health Research Institute (WCHRI) Hair Massacure Fund, University of Alberta to JRBD and DDE. JRBD is a Canada Research Chair in Molecular Medicine. ZHM is the recipient of the Alberta Innovates Health Solutions and CIHR postdoctoral fellowship awards. DDE holds the Muriel & Ada Hole Kids with Cancer Society Chair in Pediatric Oncology, University of Alberta. BNZ is supported by the National Heart, Lung, and Blood Institute grant R01HL151740 and the National Institutes of Health?s National Center for Advancing Translational Sciences grant UL1TR002494. SS is supported by Graduate Student Scholarships from WCHRI and Alberta Innovates.

Publisher Copyright:
© 2021 Federation of European Biochemical Societies.

Keywords

  • cancer
  • doxorubicin
  • heart
  • inflammation
  • NLRP3
  • resveratrol

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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