Daidzein normalized gentamicin-induced nephrotoxicity and associated pro-inflammatory cytokines in MDCK and zebrafish: Possible mechanism of nephroprotection

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2022-08, Vol.258, p.109364-109364, Article 109364
• Main Authors: Guru, Ajay, Sudhakaran, Gokul, Velayutham, Manikandan, Murugan, Raghul, Pachaiappan, Raman, Mothana, Ramzi A., Noman, Omar M., Juliet, Annie, Arockiaraj, Jesu
• Format: Article
• Language: English
• Subjects: Anti-inflammation; Antioxidant; Daidzine nephroprotection; Gentamicin toxicity; Kidney
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2022.109364

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. [Display omitted] •Daidzein inhibited oxidative stress, inflammation, and apoptosis in induced MDCK cells and zebrafish model.•Daidzein reduced lipid peroxidation and increased antioxidant enzymes in both MDCK cells and zebrafish model stressed with gentamycin nephrotoxicity.•Histopathological changes normalized by daidzein in renal injury induced by gentamycin nephrotoxicity.•TNF-α, COX-2, IL-1β, and iNOs expression in zebrafish kidney challenged with gentamycin nephrotoxicity was suppressed by daidzein.