Ashari Sorour, Karami Mohammad, Shokrzadeh Mohammad, Bagheri Abouzar, Ghandadi Morteza, Ranaee Mohammad, Dashti Ayat, Mohammadi Hamidreza
Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Toxicol Res (Camb). 2022 Mar 3;11(2):272-285. doi: 10.1093/toxres/tfac006. eCollection 2022 Apr.
This study aimed to evaluate the possible protective effects of quercetin, a natural flavonoid, against nephrotoxicity induced by Di (2-ethylhexyl) phthalate (DEHP) in kidney tissue of rats and human embryonic kidney (HEK) 293 cell line. The HEK-293 cells were treated with different concentrations of quercetin 24 h before treatment with monoethylhexyl phthalate (MEHP). Male rats were treated with 200-mg/kg DEHP, 200-mg/kg DEHP plus quercetin (50 and 100 mg/kg), and 200-mg/kg DEHP plus vitamin E (20 mg/kg) for 45 days by gavage. Quercetin treatment reduced cytotoxicity and oxidative damage inducing by MEHP in HEK-293 cells. The in vivo findings showed that 100-mg/kg quercetin significantly suppressed DEHP-induced kidney damage. For exploring the involved mechanisms, the expressions of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor kappa B (NFκB), and tumor necrosis factor alpha (TNFα) genes were determined via real-time Polymerase chain reaction (PCR) assay. High dose of quercetin significantly decreased the gene expressions of NF-κB and TNFα, whereas the alternations of Nrf2 and HO-1 gene expressions were not significant in quercetin groups in compared with DEHP group. These findings suggested that the suppression of DEHP-induced nephrotoxicity via quercetin is correlated, at least in part, with its potential to regulate NF-κB signaling pathway.
本研究旨在评估天然黄酮类化合物槲皮素对大鼠肾组织和人胚肾（HEK）293细胞系中邻苯二甲酸二（2-乙基己基）酯（DEHP）诱导的肾毒性的潜在保护作用。在用单乙基己基邻苯二甲酸酯（MEHP）处理前24小时，用不同浓度的槲皮素处理HEK-293细胞。雄性大鼠通过灌胃给予200mg/kg DEHP、200mg/kg DEHP加槲皮素（50和100mg/kg）以及200mg/kg DEHP加维生素E（20mg/kg），持续45天。槲皮素处理降低了MEHP在HEK-293细胞中诱导的细胞毒性和氧化损伤。体内研究结果表明，100mg/kg槲皮素显著抑制了DEHP诱导的肾损伤。为了探究其中涉及的机制，通过实时聚合酶链反应（PCR）测定法检测核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）、核因子κB（NFκB）和肿瘤坏死因子α（TNFα）基因的表达。高剂量的槲皮素显著降低了NF-κB和TNFα的基因表达，而与DEHP组相比，槲皮素组中Nrf2和HO-1基因表达的变化不显著。这些发现表明，槲皮素抑制DEHP诱导的肾毒性至少部分与其调节NF-κB信号通路的潜力相关。
