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Ameliorate impacts of scopoletin against vancomycin-induced intoxication in rat model through modulation of Keap1-Nrf2/HO-1 and IκBα-P65 NF-κB/P38 MAPK signaling pathways: Molecular study, molecular docking evidence and network pharmacology analysis.
- Source :
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International immunopharmacology [Int Immunopharmacol] 2022 Jan; Vol. 102, pp. 108382. Date of Electronic Publication: 2021 Nov 28. - Publication Year :
- 2022
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Abstract
- Nephrotoxicity is an indication for the damage of kidney-specific detoxification and excretion mechanisms by exogenous or endogenous toxicants. Exposure to vancomycin predominantly results in renal damage and losing the control of body homeostasis. Vancomycin-treated rats (200 mg/kg/once daily, for seven consecutive days, i.p.) revealed significant increase in serum pivotal kidney function, oxidative stress, and inflammatory biomarkers. Histologically, vancomycin showed diffuse acute tubular necrosis, denudation of epithelium and infiltration of inflammatory cells in the lining tubular epithelium in cortical portion. In the existing study, the conservative consequences of scopoletin against vancomycin nephrotoxicity was investigated centering on its capacity to alleviate oxidative strain and inflammation through streamlining nuclear factor (erythroid-derived-2) like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling and prohibiting the nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (p38 MAPK) pathway. With respect to vancomycin group, scopoletin pretreatment (50 mg/kg/once daily, i.p.) efficiently reduced kidney function, oxidative stress biomarkers and inflammatory mediators. Moreover, histological and immunohistochemical examination of scopoletin-treated group showed remarkable improvement in histological structure and reduced vancomycin-induced renal expression of iNOS, NF-κB and p38 MAPK. In addition, scopoletin downregulated (Kelch Like ECH Associated Protein1) Keap1, P38MAPK and NF-κB expression levels while upregulated renal expression levels of regulatory protein (IκBα), Nrf2 and HO-1. Furthermore, molecular docking and network approach were constructed to study the prospect interaction between scopoletin and the targeted proteins that streamline oxidative stress and inflammatory pathways. The present investigations elucidated that scopoletin co-treatment with vancomycin may be a rational curative protocol for mitigation of vancomycin-induced renal intoxication.<br /> (Copyright © 2021. Published by Elsevier B.V.)
- Subjects :
- Animals
Cytokines blood
Heme Oxygenase (Decyclizing) genetics
Heme Oxygenase (Decyclizing) immunology
Kelch-Like ECH-Associated Protein 1 genetics
Kelch-Like ECH-Associated Protein 1 immunology
Kidney drug effects
Kidney immunology
Kidney pathology
Kidney Diseases chemically induced
Kidney Diseases immunology
Kidney Diseases pathology
Male
NF-E2-Related Factor 2 genetics
NF-E2-Related Factor 2 immunology
NF-KappaB Inhibitor alpha genetics
NF-KappaB Inhibitor alpha immunology
Nitric Oxide Synthase Type II immunology
Protective Agents pharmacology
Rats, Wistar
Scopoletin pharmacology
Transcription Factor RelA genetics
Transcription Factor RelA immunology
p38 Mitogen-Activated Protein Kinases genetics
p38 Mitogen-Activated Protein Kinases immunology
Rats
Anti-Bacterial Agents
Kidney Diseases drug therapy
Protective Agents therapeutic use
Scopoletin therapeutic use
Signal Transduction drug effects
Vancomycin
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 102
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34848155
- Full Text :
- https://doi.org/10.1016/j.intimp.2021.108382