Eat Your Broccoli: Oxidative Stress, NRF2, and Sulforaphane in Chronic Kidney Disease

Abstract

The mainstay of therapy for chronic kidney disease is control of blood pressure and proteinuria through the use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) that were introduced more than 20 years ago. Yet, many chronic kidney disease (CKD) patients still progress to end-stage kidney disease-the ultimate in failed prevention. While increased oxidative stress is a major molecular underpinning of CKD progression, no treatment modality specifically targeting oxidative stress has been established clinically. Here, we review the influence of oxidative stress in CKD, and discuss regarding the role of the Nrf2 pathway in kidney disease from studies using genetic and pharmacologic approaches in animal models and clinical trials. We will then focus on the promising therapeutic potential of sulforaphane, an isothiocyanate derived from cruciferous vegetables that has garnered significant attention over the past decade for its potent Nrf2-activating effect, and implications for precision medicine.

Keywords: GSTM1; Nrf2; chronic kidney disease; oxidative stress; sulforaphane.

Figure 1

(A) Glucoraphanin content in the seeds of various Brassica vegetables. Data summarized from West et al. [88]. (B) Antioxidant ability of extracts of various Brassica vegetables, measured as quinone reductase activity induced in Hepa 1c1c7 murine hepatoma cells. Data summarized from Prochaska et al. [89].

Figure 2

Sulforaphane targets Nrf2 pathway to prevent kidney disease progression. Glucoraphanin in cruciferous vegetables is hydrolyzed to sulforaphane by the enzyme myrosinase or by the gut microbiome. Sulforaphane inhibits the KEAP-1-mediated degradation of Nrf2, allowing Nrf2 to migrate from the cell cytoplasm into the nucleus where it binds to the antioxidant responsive element (ARE) in the promoter regions of Nrf2 target genes, thereby increasing their transcription, and hence their activities. The result is a decrease in ROS and factors involved in inflammation and fibrosis. Image of cruciferous vegetables taken from https://www.eatright.org/food/vitamins-and-supplements/nutrient-rich-foods/the-beginners-guide-to-cruciferous-vegetables. Image of healthy and diseased kidney taken from https://www.nephrologyspecialistsoftulsa.com/chronic-kidney-disease.php.