Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India.
Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India.
Comp Biochem Physiol C Toxicol Pharmacol. 2022 Aug;258:109364. doi: 10.1016/j.cbpc.2022.109364. Epub 2022 May 4.
This study investigates the therapeutic activity of daidzein, an isoflavone that occurs naturally in plants and herbs, against gentamicin-induced nephrotoxicity in Madin-Darby canine kidney (MDCK) cells in-vitro and zebrafish model in-vivo. The in-vitro studies revealed that daidzein protected MDCK cells from gentamicin-induced inflammation by suppressing oxidative stress and apoptosis. The zebrafish were divided into groups and injected with gentamicin (140 mg/mL) to induce nephrotoxic conditions. After injection, renal dysfunction, nitric oxide production, antioxidant consumption, exaggerated apoptosis, and inflammation were all observed in the zebrafish model. We also observed that during kidney inflammation in zebrafish, pro-inflammatory cytokines such as cyclooxygenase (COX-2), tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β) are upregulated. Furthermore, daidzein treatment after gentamicin injection showed a strong protective anti-inflammatory effect. Daidzein activity was associated with an increase in antioxidant biomarkers such as superoxide dismutase (SOD) and glutathione reductase (GSH), whereas lipid peroxidation (LPO) and nitric oxide (NO) production were decreased in a dose-dependent factor. Moreover, histopathological alteration caused by gentamicin in zebrafish kidneys was normalized due to daidzein treatment. Daidzein also downregulated the pro-inflammatory cytokines gene expression in gentamicin-induced kidney inflammation in zebrafish. These results revealed that daidzein could potentially prevent nephrotoxic conditions through pro-inflammatory cytokines inhibition and its antioxidant property.
本研究调查了大豆黄酮（一种天然存在于植物和草药中的异黄酮）对庆大霉素诱导的 Madin-Darby 犬肾（MDCK）细胞体外和斑马鱼体内肾毒性的治疗活性。体外研究表明，大豆黄酮通过抑制氧化应激和细胞凋亡来保护 MDCK 细胞免受庆大霉素诱导的炎症。将斑马鱼分为几组，并注射庆大霉素（140mg/mL）以诱导肾毒性。注射后，在斑马鱼模型中观察到肾功能障碍、一氧化氮产生、抗氧化剂消耗、过度凋亡和炎症。我们还观察到，在斑马鱼肾脏炎症期间，促炎细胞因子如环加氧酶（COX-2）、肿瘤坏死因子（TNF-α）和白细胞介素-1β（IL-1β）上调。此外，庆大霉素注射后给予大豆黄酮显示出强烈的抗炎保护作用。大豆黄酮的活性与抗氧化生物标志物如超氧化物歧化酶（SOD）和谷胱甘肽还原酶（GSH）的增加有关，而脂质过氧化（LPO）和一氧化氮（NO）的产生则呈剂量依赖性降低。此外，由于大豆黄酮的治疗，庆大霉素引起的斑马鱼肾脏的组织病理学改变得到了正常化。大豆黄酮还下调了庆大霉素诱导的斑马鱼肾脏炎症中的促炎细胞因子基因表达。这些结果表明，大豆黄酮可能通过抑制促炎细胞因子及其抗氧化特性来预防肾毒性。
