دورية أكاديمية
Crocin attenuates cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β activity: Involvement of miRNA-9 and miRNA-29.
| العنوان: | Crocin attenuates cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β activity: Involvement of miRNA-9 and miRNA-29. |
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| المؤلفون: | Khedr LH; Pharmacology & Toxicology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt. Electronic address: lobna.hatem@miuegypt.edu.eg., Rahmo RM; Pharmacology & Toxicology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt., Farag DB; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt., Schaalan MF; Pharmacy Practice & Clinical Pharmacy Department, Faculty of Pharmacy, Translational and Clinical Research Unit, Misr International University (MIU), Cairo, Egypt., El Magdoub HM; Biochemistry Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt. |
| المصدر: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2020 Jun; Vol. 140, pp. 111307. Date of Electronic Publication: 2020 Apr 04. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 8207483 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-6351 (Electronic) Linking ISSN: 02786915 NLM ISO Abbreviation: Food Chem Toxicol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Exeter : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1982- |
| مواضيع طبية MeSH: | Antineoplastic Agents/*toxicity , Carotenoids/*pharmacology , Cisplatin/*toxicity , Liver/*drug effects , Membrane Proteins/*metabolism , NF-kappa B/*metabolism , Toll-Like Receptor 4/*metabolism , Transforming Growth Factor beta/*metabolism, Animals ; Liver/metabolism ; Male ; Molecular Docking Simulation ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Signal Transduction/drug effects |
| مستخلص: | TLR4-induced mitigation of the BMP down-regulation and activin membrane bound inhibitor (BAMBI) and the consequent enhancement of the transforming growth factor-beta (TGF-β) profibrogenic signaling has not yet been studied in cisplatin (CIS)-induced hepatotoxicity. miRNA-9 and29 have been previously reported to modulate TLR4 signaling via either tempering the expression of nuclear factor kappa-B p50 (NF-κB p50) or downregulation of extracellular matrix genes respectively. Hence we aimed to investigate the involvement of TLR4-induced modulation of TGF-β receptor 1 (TGF-βR1) signaling as well as the implication of miRNA-9 and 29 in CIS-induced hepatotoxicity. Moreover, we examined the ability of the phytochemical; crocin (CROC); to interact with either TLR4 or TGF-βR1 through a molecular docking study and subsequently explore its capability to attenuate CIS-induced hepatotoxicity. CROC pretreatment ameliorated the CIS-induced enhancement of TLR4 and TGF-β signaling and enhanced the expression of BAMBI, miRNA-9 and 29. Accordingly, it may be assumed that the protective effect of CROC against CIS-induce hepatotoxicity is mediated via the crosstalk of TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β1 activity in addition to the up-regulation of miRNA-9 and 29. These findings came in alignment with our molecular docking results; emphasizing the molecular antagonistic activity of CROC in both TLR4 and TGF-βR1. 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. Data are presented as mean ± S.E.M (n = 8). For comparisons among groups, one-way ANOVA followed by the post hoc “Tukey's Multiple Comparison Test” was utilized. *p < 0.05 significant in comparison to CONT, (#)p < 0.05 significant in comparison to CIS. CONT: Control, CROC: Crocin (200 mg/kg i.p.), CIS: Cisplatin (5 mg/kg i.p). (−): Nil, (+): Mild/less than 20% of examined sections, (++): Moderate/21–40% of examined sections and (+++): sever/more than 40% of examined sections. (Copyright © 2020 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: BAMBI; Cisplatin; Crocin; Hepatotoxicity; Molecular docking; TGF-βR1; TLR4 |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Bambi protein, rat) 0 (Membrane Proteins) 0 (NF-kappa B) 0 (Tlr4 protein, rat) 0 (Toll-Like Receptor 4) 0 (Transforming Growth Factor beta) 36-88-4 (Carotenoids) 877GWI46C2 (crocin) Q20Q21Q62J (Cisplatin) |
| تواريخ الأحداث: | Date Created: 20200408 Date Completed: 20210219 Latest Revision: 20210219 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.fct.2020.111307 |
| PMID: | 32259551 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-6351 |
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| DOI: | 10.1016/j.fct.2020.111307 |