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Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity
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
Guizhou 2nd Provincial People's Hospital, Guizhou, China
Department of Scientific Research, Innoscience Research SDN BHD, Subang Jaya, 47650, Selangor, Malaysia
Department of Scientific Research, Innoscience Research SDN BHD, Subang Jaya, 47650, Selangor, Malaysia
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
Cardiovascular Medicine Department, Shaanxi Traditional Chinese Medicine Hospital, No. 2 Xihuamen Street, Lianhu District, Xi'an, Shaanxi Province, China
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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