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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.241 5-Year IF: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2019029341
pages 143-152

Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity

Miao Chen
Department of Cardiology, The Second People's Hospital of Yunnan Province, Kunming, Yunnan, China
Vijaya Paul Samuel
Department of Anatomy, RAK College of Medicine, RAK Medical and Health Sciences University, Ras Al Khaimah, UAE
Yi Wu
Guizhou 2nd Provincial People's Hospital, Guizhou, China
Minyan Dang
Department of Scientific Research, Innoscience Research SDN BHD, Subang Jaya, 47650, Selangor, Malaysia
Yukiat Lin
Department of Scientific Research, Innoscience Research SDN BHD, Subang Jaya, 47650, Selangor, Malaysia
Raghava Sriramaneni
Department of Human Oncology, University of Wisconsin, Madison, WI, USA
Sushil Kumar Sah
Birat Medical College, Biratnagar, Nepal
Gopala Krishna Chinnaboina
AM Reddy Memorial College of Pharmacy, Narasaraopet, Guntur, India
Guangping Zhang
Cardiovascular Medicine Department, Shaanxi Traditional Chinese Medicine Hospital, No. 2 Xihuamen Street, Lianhu District, Xi'an, Shaanxi Province, China

ABSTRACT

The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.

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