Apigenin Protects Against Renal Tubular Epithelial Cell Injury and Oxidative Stress by High Glucose via Regulation of NF-E2-Related Factor 2 (Nrf2) Pathway.

Abstract

BackgroundDiabetic nephropathy (DN) is a disease characterized by oxidative stress and apoptosis of renal tubular epithelial cells driven by hyperglycemia. Apigenin is a flavonoid compound that possesses potent anti-apoptotic properties. The present study aimed to explore the protective effects and underlying mechanisms of apigenin on renal tubular epithelial cells exposed to hyperglycemia.Material/MethodsHuman renal epithelial cell HK-2 were incubated to D-glucose to establish in vitro DN model. The cell viability, lactate dehydrogenase (LDH) release, apoptosis and oxidative stress were evaluated. qRT-PCR was performed to determine the mRNA levels of NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Western blot analysis was performed to measure the protein expressions of Nrf2.ResultsIn HK-2 cells, high glucose reduced cell viability in a concentration- and time-dependent manner. Apigenin suppressed the decrease in cell viability and increase in supernatant LDH release at 100 and 200 μM after 48-h treatment. Apigenin reduced apoptotic rate and pro-inflammatory cytokines production. Apigenin suppressed oxidative stress and increased mRNA expressions of Nrf2 and HO-1. Inhibition of Nrf2 using small interfering RNA (siRNA), or cotreatment with LY294002, an inhibitor of PI3K/Akt, abolished the protective effect on high glucose-induced injury, oxidative stress, and pro-inflammatory cytokines production by apigenin. LY294002 also attenuated the increase in Nrf2 protein by apigenin in high glucose-treated HK-2 cells.ConclusionsApigenin protects renal tubular epithelial cells against high glucose-induced injury through suppression of oxidative stress and inflammation via activation of the Nrf2 pathway.