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Abstract Title:

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

Abstract Source:

Comp Biochem Physiol C Toxicol Pharmacol. 2022 May 4 ;258:109364. Epub 2022 May 4. PMID: 35523404

Abstract Author(s):

Ajay Guru, Gokul Sudhakaran, Manikandan Velayutham, Raghul Murugan, Raman Pachaiappan, Ramzi A Mothana, Omar M Noman, Annie Juliet, Jesu Arockiaraj

Article Affiliation:

Ajay Guru

Abstract:

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 cytokinessuch 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.

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