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Tytuł pozycji:

New insights into the protection of growth hormone in cisplatin-induced nephrotoxicity: The impact of IGF-1 on the Keap1-Nrf2/HO-1 signaling.

Tytuł:
New insights into the protection of growth hormone in cisplatin-induced nephrotoxicity: The impact of IGF-1 on the Keap1-Nrf2/HO-1 signaling.
Autorzy:
Mahran YF; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.. Electronic address: Jassie_.
Źródło:
Life sciences [Life Sci] 2020 Jul 15; Vol. 253, pp. 117581. Date of Electronic Publication: 2020 Mar 21.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
MeSH Terms:
Acute Kidney Injury/*prevention & control
Cisplatin/*adverse effects
Growth Hormone/*metabolism
Heme Oxygenase-1/*metabolism
Insulin-Like Growth Factor I/*metabolism
Kelch-Like ECH-Associated Protein 1/*metabolism
NF-E2-Related Factor 2/*metabolism
Acute Kidney Injury/chemically induced ; Acute Kidney Injury/pathology ; Animals ; Anti-Infective Agents/adverse effects ; Anti-Infective Agents/metabolism ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/metabolism ; Antioxidants/adverse effects ; Antioxidants/pharmacology ; Caspase 3/metabolism ; Cisplatin/metabolism ; Disease Models, Animal ; Epoxide Hydrolases/metabolism ; Growth Hormone/pharmacology ; HMGB Proteins/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; Human Growth Hormone ; Humans ; Kidney/drug effects ; Kidney/metabolism ; Kidney/pathology ; Male ; NF-kappa B/metabolism ; Oxidative Stress/drug effects ; Rats ; Signal Transduction
Contributed Indexing:
Keywords: Cisplatin; Growth hormone; HMGB-1; HO-1; IGF-1; Keap1; Nephrotoxicity; Nrf2
Substance Nomenclature:
0 (Anti-Infective Agents)
0 (Antineoplastic Agents)
0 (Antioxidants)
0 (HMGB Proteins)
0 (HSP70 Heat-Shock Proteins)
0 (Kelch-Like ECH-Associated Protein 1)
0 (NF-E2-Related Factor 2)
0 (NF-kappa B)
12629-01-5 (Human Growth Hormone)
67763-96-6 (Insulin-Like Growth Factor I)
9002-72-6 (Growth Hormone)
EC 1.14.14.18 (Heme Oxygenase-1)
EC 3.3.2.- (Epoxide Hydrolases)
EC 3.4.22.- (Caspase 3)
Q20Q21Q62J (Cisplatin)
Entry Date(s):
Date Created: 20200327 Date Completed: 20200615 Latest Revision: 20200615
Update Code:
20240105
DOI:
10.1016/j.lfs.2020.117581
PMID:
32209424
Czasopismo naukowe
Aims: Cisplatin (CDDP) is an effective antineoplastic agent, however, its serious nephrotoxicity limits therapeutic use. Human growth hormone (hGH) has proved antioxidant and anti-inflammatory activities. The present study aimed to investigate the nephroprotective effects of hGH against CDDP-induced nephrotoxicity and the mechanisms underlying this nephroprotection.
Main Methods: Male albino rats injected with CDDP (7 mg/kg) and nephrotoxicity indices, oxidative stress and inflammatory biomarkers (high mobility group box protein-1 (HMGB-1), soluble epoxide hydrolase (sEH), and nuclear factor-kappa B (NF-κB)) were assessed. Also, insulin-like growth factor-1 (IGF-1) and Nuclear factor-erythroid-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway were assessed.
Key Findings: hGH (1 mg/kg) improved kidney function and antioxidant systems and showed intact renal tubular epithelium. Cisplatin upregulated the HMGB-1/NF-κB and downregulated Nrf2/HO-1 pathways which were reversed by hGH and aligned with increased renal IGF-1 expression. Also, IGF-1/sEH crosstalk might be involved in hGH nephroprotection. Moreover, hGH downregulated HSP70 and caspase-3 expressions.
Significance: these results concluded that hGH can attenuate the inflammation and oxidative stress attained by CDDP probably through inhibition of Nrf2/HO-1 pathway. We also suggested that Keap1/Nrf2-mediated upregulation of the antioxidant HO-1 might inhibit HMGB-1/NF-κB signaling and thus provide the principal protection mechanism offered by hGH against CDDP-induced kidney injury.
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 © 2020 Elsevier Inc. All rights reserved.)

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