Hyperoside protects human kidney‑2 cells against oxidative damage induced by oxalic acid

Abstract

The majority of renal calculi (kidney stones) are calcium stones. Oxidative damage to renal tubular epithelial cells induced by reactive oxygen species (ROS) is the predominant cause of calcium oxalate stone formation. Hyperoside (Hyp) is a flavonol glycoside extracted from medicinal plants and appears to exhibit potent antioxidant activity in various cells. The aim of the present study was to investigate the protective effect of Hyp on renal cells exposed to oxidative stress simulated by oxalic acid (OA), and to determine whether the underlying mechanism involves the nuclear factor E2‑related factor2 (Nrf2)‑antioxidative response element signaling pathway. The study determined the indicators of high oxidative stress, including ROS and hydrogen peroxide (H2O2) in human kidney‑2 cells and the results demonstrated that the levels of ROS, as evaluated by flow cytometry, and H2O2 were significantly increased following treatment with OA (5 mmol/l) for 24 h (OA group), compared with those in the untreated control group. The increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in these cells explained this observation, as it is a major source of ROS. The results demonstrated that, in the OA group, the adhesion of calcium oxalate crystals and lactate dehydrogenase (LDH) were significantly increased, and MTT assay demonstrated that cell viability was inhibited, compared with the control, which indicated that severe injury of cells was induced by OA. However, when the cells were pre‑treated with Hyp prior to treatment with OA (drug group), the levels of ROS and H2O2, and the activities of NADPH oxidase and LD were increased, and the adhesion of calcium oxalate crystals to cells was reduced, compared with the OA group. Western blot analysis and reverse transcription‑quantitative polymerase chain reaction demonstrated that the protein and mRNA expression levels of Nrf2, heme oxygenase‑1 (HO‑1) and NAD(P)H: quinineoxidoreductase 1 (NQO1) in the Hyp groups were significantly increased, compared with those in the OA group, with the exception of Nrf2 mRNA. These results suggested that Hyp had a marked protective effect on renal cells against the oxidative damage and cytotoxicity simulated by OA. This is the first report, to the best of our knowledge, demonstrating that the ability of Hyp to enhance the endogenous functions of antioxidation and detoxification in cells may involve the Nrf2/HO‑1/NQO1 pathway.

Hyperoside Attenuates Bleomycin-Induced Pulmonary Fibrosis Development in Mice

“…Hyp is known to exert many pharmacological actions, including antioxidant and anti-fibrosis effects (Ye et al, 2017;Zou et al, 2017). Studies have shown that Hyp protects against oxidative damage and cytotoxicity induced by oxalic acid in human kidney-2 cells (Chen et al, 2018). Hyp has also been revealed to prevent heart failure-induced liver fibrosis (Guo et al, 2019).…”

Regulation on Calcium Oxalate Crystallization and Protection on HK-2 Cells of Tea Polysaccharides with Different Molecular Weights

“…After the cells were injured, excessive ROS was generated by affecting NADPH oxidase activity. ROS accumulation in cells will cause oxidative stress reaction [31]. TPS preprotection can significantly reduce the ROS level of cells ( Figure 10), thereby improving the antioxidant capacity of cells.…”

Hyperoside protects against cerebral ischemia-reperfusion injury by alleviating oxidative stress, inflammation and apoptosis in rats

“…Previous studies have found that hyperoside also has inhibits oxidative stress, reduces inflammatory response and apoptosis [11][12][13], and it is oxidative stress, inflammatory response and apoptosis that are closely related to the occurrence and development of cerebral I/R injury [14,15]. The protective effect of hyperoside against the cerebral I/R injury has been reported, but the underlying mechanism has not been clarified [16,17].…”