Genistein Ameliorates Ischemia/Reperfusion-Induced Renal Injury in a SIRT1-Dependent Manner

Abstract

Renal ischemia/reperfusion (I/R) injury continues to be a complicated situation in clinical practice. Genistein, the main isoflavone found in soy products, is known to possess a wide spectrum of biochemical and pharmacological activities. However, the protective effect of genistein on renal I/R injury has not been well investigated. In the current study, we explore whether genistein exhibits its renal-protective effects through SIRT1 (Sirtuin 1) in I/R-induced mice model. We found the treatment of genistein significantly reduced renal I/R-induced cell death, simultaneously stimulating renal cell proliferation. Meanwhile, SIRT1 expression was up-regulated following the administration of genistein in renal region. Furthermore, pharmacological inhibition or shRNA-mediated depletion of SIRT1 significantly reversed the protective effect of genistein on renal dysfunction, cellular damage, apoptosis, and proliferation following I/R injury, suggesting an indispensible role of the increased SIRT1 expression and activity in this process. Meanwhile, the reduced p53 and p21 expression and increased PCNA (Proliferating Cell Nuclear Antigen) expression were blocked after the depletion of SIRT1 compared with the genistein treatment group in the renal I/R process. Hence, our results provided further experimental basis for the potential use of genistein for the treatment of kidney disease with deficiency of SIRT1 activity.

Renalase Attenuates Mouse Fatty Liver Ischemia/Reperfusion Injury through Mitigating Oxidative Stress and Mitochondrial Damage via Activating SIRT1

“…SIRT1, a class III histone deacetylase whose activity is dependent on NAD + , regulates a wide array of cellular processes, including oxidative stress, metabolism, apoptosis, and aging by deacetylating both histone and nonhistone proteins [61]. SIRT1 plays a protective role against IR injury in the heart [61], kidney [62], brain [63], and liver [64]. Previous studies have demonstrated that SIRT1 deacetylates its downstream targets, including NF-κB, Foxos, p53, and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), to regulate apoptosis, inflammation, and oxidative stress and protect organs from IR injury [65].…”

A novel method for the highly efficient biotransformation of genistein from genistin using a high-speed counter-current chromatography bioreactor

“…Ohwi and Sophora japonica L. Genistein is structurally similar to estrogen and has a number of biological properties that can prove benecial in alleviating a variety of health conditions including kidney disease, menopausal symptoms, neuronal loss, Alzheimer's disease, and cancer. [1][2][3][4][5][6][7] Because of this broad range of biological properties, genistein has gained attention as a food additive and dietary supplement. Currently, there is an enormous demand for genistein in health and food products.…”

Anti‐Inflammatory and Antioxidative Properties of Isoflavones Provide Renal Protective Effects Distinct from Those of Dietary Soy Proteins against Diabetic Nephropathy

“…[ 22 ] Isoflavones supplementation failed to inhibit hyperglycaemia in KKAy mice, unlike in type 1 diabetes model, probably due to a pancreatic injury in this T2D model. Additionally, genistein reduced renal tubular cell death caused by ischemia/reperfusion injury [ 23 ] and cisplatin‐induced injury. [ 24 ] Furthermore, genistein attenuates epithelial–mesenchymal transition and inhibits profibrotic protein expression in renal tubular cells stimulated by parathyroid hormones.…”