Dihydromyricetin protects against gentamicin-induced nephrotoxicity via upregulation of renal SIRT3 and PAX2.

Autor: Matouk AI; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt. Electronic address: asmaa.ahmed@mu.edu.eg., Awad EM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt., Mousa AAK; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada., Abdelhafez SMN; Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia, Egypt., Fahmy UA; Center of Research Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia., El-Moselhy MA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt; Clinical Pharmacy and Pharmacology Department, Ibn Sina National College for Medical Studies, Jeddah 21589, Saudi Arabia., Abdel-Naim AB; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia., Anter A; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Jan 01; Vol. 336, pp. 122318. Date of Electronic Publication: 2023 Nov 29.
DOI: 10.1016/j.lfs.2023.122318
Abstrakt: Aim: Gentamicin-induced nephrotoxicity limits its widespread use as an effective antibacterial agent. Oxidative stress, inflammatory cytokines and apoptotic cell death are major participants in gentamicin-induced nephrotoxicity. We therefore, investigated whether dihydromyricetin (DHM), the antioxidant and anti-inflammatory flavonoid, could protect against the nephrotoxic effects of gentamicin.
Methods: Male Wistar rats administrated gentamicin (100 mg/kg/day, i.p.) for 8 days. DHM (400 mg/kg, p.o.) was concurrently given with gentamicin for 8 days. Control group received the vehicle of DHM and gentamicin. Histopathological examinations, biochemical measurements and immunohistochemical analyses were done at the end of the study.
Key Findings: Treatment with DHM improved the gentamicin induced deterioration of renal functions; serum levels of urea, creatinine and cystatin-C as well as urinary levels of Kim-1 and NGAL, the sensitive indicators for early renal damage, were declined. Additionally, DHM abrogated gentamicin-induced changes in kidney morphology. These nephroprotective effects were possibly mediated via decreasing renal gentamicin buildup, activating the antioxidant enzymes GSH, SOD and CAT and decreasing lipid peroxidation and nitric oxide levels. Further, DHM suppressed renal inflammation and apoptotic cell death by decreasing the expression of nuclear factor-kappa B (NF-κB), TNF-alpha and caspase-3. These effects were correlated to the upregulation of renal SIRT3 expression. Also, DHM activated the regeneration and replacement of injured tubular cells with new ones via enhancing PAX2 expression.
Significance: DHM is a promising therapeutic target that could prevent acute renal injury induced by gentamicin and help renal tubular cells to recover through its antioxidant, anti-inflammatory and antiapoptotic properties.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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