Genistein Prevents Nitric Oxide Deficiency-Induced Cardiac Dysfunction and Remodeling in Rats

Anuson Poasakate; Putcharawipa Maneesai; Siwayu Rattanakanokchai; Sarawoot Bunbupha; Terdthai Tong-Un; Poungrat Pakdeechote

doi:10.3390/antiox10020237

Genistein Prevents Nitric Oxide Deficiency-Induced Cardiac Dysfunction and Remodeling in Rats

Antioxidants (Basel). 2021 Feb 4;10(2):237. doi: 10.3390/antiox10020237.

Authors

Anuson Poasakate¹, Putcharawipa Maneesai¹, Siwayu Rattanakanokchai², Sarawoot Bunbupha³, Terdthai Tong-Un¹, Poungrat Pakdeechote^{1

4}

Affiliations

¹ Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
² Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
³ Faculty of Medicine, Mahasarakham University, Maha Sarakham 44000, Thailand.
⁴ Research Institute for Human High Performance and Health Promotion, Khon Kaen University, Khon Kaen 40002, Thailand.

Abstract

Genistein is an isoflavone found in soybeans. This study evaluates the protective effects of genistein on N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension, cardiac remodeling, and dysfunction in rats. Male Wistar rats were treated with L-NAME 40 mg/kg/day together for 5 weeks, with or without genistein at a dose of 40 or 80 mg/kg/day or lisinopril 5 mg/kg/day (n = 8 per group). Genistein prevented L-NAME-induced hypertension in rats. Increases in the left ventricular weight, metalloproteinase-2, metalloproteinase-9, and collagen type I intensity were observed in L-NAME rats, and these changes were attenuated in the genistein-treated group. Genistein reduced circulating angiotensin-converting enzyme activity and angiotensin II concentrations in L-NAME rats. L-NAME increased plasma and cardiac malondialdehyde and vascular superoxide generations, as well as reductions of serum and cardiac catalase activities in rats. Plasma nitrate/nitrite were protected in the genistein-treated group. Genistein prevented the L-NAME-induced overexpression of angiotensin II receptor type I (AT₁R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 2 (gp91^phox), and transforming growth factor beta I (TGF-β1) in hypertensive rats. In conclusion, genistein exhibited a cardioprotective effect in hypertensive rats in this study. The molecular mechanisms might be mediated by suppression of oxidative stress through the Ang II/AT₁R/NADPH oxidase/TGF-β1 signaling pathway.

Keywords: MMP-2; MMP-9; cardiac function; collagen type I; fibrosis; genistein.

Abstract

Grants and funding