Abstract
Oxidative stress (OS) in renal tubular epithelial cells (RTECs) is induced by calcium oxalate (CaOx) stones and plays an important role in the pathology of CaOx nephrolithiasis. The nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important endogenous antioxidant pathway. Flavonoids are compounds with 2-phenylchromone as the basic mother nucleus and are natural antioxidant components of Lysimachia christinae. Our previous studies demonstrated that the total flavonoids from L. christinae (TFL) reduced calcium and oxalic acid concentrations in urine, thus inhibiting CaOx stone formation. We also showed that TFL can reduce OS in renal tissue. However, whether TFL inhibit the formation of CaOx stones through the Nrf2/ARE pathway requires further investigation. Here, we found that TFL protected against injury to a renal cell line and renal tissue, reduced CaOx-induced OS in renal tissue, and reduced CaOx crystal formation. In addition, TFL significantly increased nuclear Nrf2 and the expression of the downstream antioxidant genes heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1). Furthermore, TFL increased superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) content, thereby alleviating OS in RTECs. Silencing Nrf2 expression blocked the protective effect of TFL on CaOx-induced OS. Taken together, our findings indicate that TFL reduce CaOx-induced OS in renal tissue by activating the Nrf2/ARE pathway.
Highlights
Calcium oxalate (CaOx) stones account for more than 70% of renal calculi [1]. e causes of urinary stones are extremely complex
To elucidate the mechanisms underlying this phenomenon, we investigated whether the protective antioxidant effects of total flavonoids from L. christinae (TFL) on renal tissue are mediated by nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway modulation, thereby preventing renal calculus formation
After confirming that TFL reduced oxidative stress (OS) in renal tissue using in vitro and in vivo CaOx stone models, we investigated the effect of TFL on the Nrf2-ARE pathway
Summary
Calcium oxalate (CaOx) stones account for more than 70% of renal calculi [1]. e causes of urinary stones are extremely complex. ROS-induced RTEC injury and subsequent OS are closely related to the formation of renal calculi and may even be an important initiating event. E Nrf activator dimethyl fumarate can alleviate calcium deposition and renal tissue injury induced by hyperoxaluria in rats and downregulate the expression of bone morphogenetic protein 2 and osteopontin [14]. Our previous study demonstrated that TFL reduced calcium and oxalic acid concentrations in the urine, inhibiting CaOx stone formation [18]. We investigated whether TFL reduced renal tissue OS induced by CaOx stone formation via Nrf2/ARE pathway activation. TFL treatment significantly increased SOD activity and decreased malondialdehyde (MDA) content in HK-2 cells, thereby reducing OS in RTECs. Silencing Nrf expression blocked the protective effect of TFL on CaOx-induced OS. Us, TFL reduce CaOx-induced OS in renal tissue by activating the Nrf2/ARE pathway Silencing Nrf expression blocked the protective effect of TFL on CaOx-induced OS. us, TFL reduce CaOx-induced OS in renal tissue by activating the Nrf2/ARE pathway
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