Genistein protects against doxorubicin-induced cardiotoxicity through Nrf-2/HO-1 signaling in mice model.

Abstract:

:Doxorubicin (DOX)-induced cardiomyopathy is a lethal disease. DOX-induced cardiotoxic effects are attributed towards increased redox status and apoptotic signaling. In this study, we show that genistein offers protection against DOX-induced cardio toxicity in the mice model. DOX-mediated increase in serum cardiac troponin and redox markers (ROS, LPO, 4-hydroxynonenal-protein adducts [HNE] levels) was significantly reduced by genistein treatment. Significantly increased TNF-α, IL-6, IL-8 expressions during DOX-induced inflammatory responses were down regulated by genistein treatment. Further, we found that genistein regulated antioxidant response through increased Nrf-2, HO-1, NQO1 protein expressions. In addition, DOX downregulated survival proteins (p-Akt, Bcl-2) with concomitant upregulation in Erk (1/2), Bax and cleaved caspase-3 expressions. The apoptotic activation was significantly downregulated by genistein treatment through suppression of apoptosis. Altogether, these findings show that genistein protects against DOX-induced cardiotoxic effects through activation of Nrf-2/HO-1 signaling.

journal_name

Environ Toxicol

journal_title

Environmental toxicology

authors

Bai Z,Wang Z

doi

10.1002/tox.22730

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

645-651

issue

5

eissn

1520-4081

issn

1522-7278

journal_volume

34

pub_type

杂志文章