16 July 2019 : Laboratory Research
Apigenin Protects Against Renal Tubular Epithelial Cell Injury and Oxidative Stress by High Glucose via Regulation of NF-E2-Related Factor 2 (Nrf2) PathwayJichen Zhang12BE, Xuemei Zhao1B, Hongling Zhu1B, Jingnan Wang1B, Junhua Ma1CE, Mingjun Gu1AG*
Med Sci Monit 2019; 25:5280-5288
BACKGROUND: Diabetic 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 AND METHODS: Human 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.
RESULTS: In 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.
CONCLUSIONS: Apigenin protects renal tubular epithelial cells against high glucose-induced injury through suppression of oxidative stress and inflammation via activation of the Nrf2 pathway.
Keywords: Acidosis, Renal Tubular, Apigenin, Hyperglycemia, NF-E2-Related Factor 2, Cell Line, Glucose, Heme Oxygenase-1, Kidney Tubules, Phosphatidylinositol 3-Kinases, Protective Agents, Proto-Oncogene Proteins c-akt
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