Nephroprotective activity of natural products against chemical toxicants: The role of Nrf2/ARE signaling pathway

Abstract

Nephropathy can occur following exposure of the kidneys to oxidative stress. Oxidative stress is the result of reactive oxygen species (ROS) formation due to intracellular catabolism or exogenous toxicant exposure. Many natural products (NPs) with antioxidant properties have been used to demonstrate that oxidative damage‐induced nephrotoxicity can be ameliorated or at least reduced through stimulation of the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway. Nrf2 is a basic leucine zipper (bZip) transcription factor that regulates gene expression of the antioxidant response elements (ARE). Nrf2 is involved in the cellular antioxidant‐detoxification machinery. Nrf2 activation is a major mechanism of nephroprotective activity for these NPs, which facilitates its entry into the nucleus, primarily by inhibiting Kelch like‐ECH‐associated protein 1 (Keap1). The purpose of this article was to review the peer‐reviewed literature of NPs that have shown mitigating effects on renal disorder by stimulating Nrf2 and thereby suggesting potential new therapeutic or prophylactic strategies against kidney‐damaging xenobiotics.

The Cytotoxicity and Nephroprotective Activity of the Ethanol Extracts of Angelica keiskei Koidzumi Stems and Leaves against the NAPQI-Induced Human Embryonic Kidney (HEK293) Cell Line

“…In the body, NAPQI binds to selenium protein and glutamine synthetase at the S3 segment of the proximal tubule, which causes an increase of xanthine oxidase (XOD) activity; thus, the production of reactive oxygen species (ROS) is also enhanced [ 14 , 15 ]. Excess ROS production and its exposure to the kidney leads to oxidative stress and is followed by nephropathy and eventually kidney failure [ 8 , 16 ]. In this study, we investigated the cytotoxicity and nephroprotective activity of the ethanol extract of A .…”

“…Many natural products with antioxidant properties have been reported to have advantageous effects in the remedy of nephrotoxicity [ 8 ]. Angelica keiskei Koidzumi or ashitaba (a Japanese word which means tomorrow leaf) has been believed in improving health, particularly protecting the liver and kidney system, and achieving longevity.…”

Estimation the protective role of Andrographis paniculata aqueous extracts on nephrotoxicity in male rabbits treated with butylated hydroxytoluene (BHT)

“…The most significant destructive renal effects result from exposure to foreign substances or drugs, toxins, and induction of the oxidative stress. This may be followed by activation of different factors and pathways influencing and involved in kidney tissue damage, for example, nuclear factor kappa B (NF-kB) or increased production of the inflammatory cytokines like the Tumor necrosis factor and IL-6 Those changes could result in an imbalance between those inflammatory factors and cell's antioxidant defense, eventually leading to serious disorders and disease (Molaei et al,2021). The body's exposure to the BHT has led to kidneys being greatly affected due to the toxicity.…”

Resveratrol as an Adjunctive Therapy for Excessive Oxidative Stress in Aging COVID-19 Patients

“…Under normal physiological conditions, Keap1 blocks Nrf2 by retaining Nrf2 in the cytoplasm, thereby targeting it for proteasomal degradation. However, oxidative stress affects the structure of Keap1, making it incapable of inhibiting Nrf2 and retaining it in the cytoplasm [256]. Nrf2 may also be activated by the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, particularly in response to RSV [257].…”