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Tytuł:
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Concerted outcome of metformin and low dose of radiation in modulation of cisplatin induced uremic encephalopathy via renal and neural preservation.
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Autorzy:
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Hasan HF; Radiation Biology Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt. Electronic address: hes_.
Rashed LA; Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
El Bakary NM; Radiation Biology Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
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Źródło:
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Life sciences [Life Sci] 2021 Jul 01; Vol. 276, pp. 119429. Date of Electronic Publication: 2021 Mar 27.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
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MeSH Terms:
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Gamma Rays*
Biomarkers/*metabolism
Brain Diseases/*prevention & control
Cisplatin/*toxicity
Metformin/*pharmacology
Neuroprotective Agents/*pharmacology
Uremia/*prevention & control
Animals ; Antineoplastic Agents/toxicity ; Brain Diseases/chemically induced ; Brain Diseases/metabolism ; Brain Diseases/pathology ; Dose-Response Relationship, Radiation ; Glutathione/metabolism ; Hypoglycemic Agents/pharmacology ; Male ; NF-kappa B/metabolism ; Oxidative Stress ; Rats ; Tumor Necrosis Factor-alpha/metabolism ; Uremia/chemically induced ; Uremia/metabolism ; Uremia/pathology
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Contributed Indexing:
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Keywords: Cisplatin; Low dose radiation; Metformin; Uremic encephalopathy
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Substance Nomenclature:
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0 (Antineoplastic Agents)
0 (Biomarkers)
0 (Hypoglycemic Agents)
0 (NF-kappa B)
0 (Neuroprotective Agents)
0 (Tumor Necrosis Factor-alpha)
9100L32L2N (Metformin)
GAN16C9B8O (Glutathione)
Q20Q21Q62J (Cisplatin)
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Entry Date(s):
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Date Created: 20210331 Date Completed: 20210503 Latest Revision: 20210503
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Update Code:
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20240105
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DOI:
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10.1016/j.lfs.2021.119429
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PMID:
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33785333
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Aim: The therapeutic expediency of cisplatin was limited due to its nephrotoxic side effects, so this study planned to assess the nephrotic and neuroprotective impact of metformin (MET) and low-dose radiation (LDR) in cisplatin-prompted kidney injury and uremic encephalopathy (UE).
Methods: The effect of the 10-day MET treatment (200 mg/kg, orally) and/or fractionated LDR (0.25 Gy, of the total dose of 0.5 Gy, 1st and 7th day, respectively) on (5 mg/kg, intraperitoneally) cisplatin as a single dose was administered at the 5th day. Serum urea, creatinine and renal kidney injury molecule-1 were measured for the assessment of kidney function. Furthermore, the antioxidant potential in the renal and brain tissues was evaluated through, malondialdehyde and reduced glutathione estimation. Moreover, renal apoptotic markers: AMP-activated protein kinase, lipocalin, B-cell lymphoma 2 associated X protein, B-cell lymphoma 2, P53 and beclin 1 were estimated. UE was evaluated through the determination of serum inflammatory markers: nuclear factor kappa B, tumor-necrosis factor-α and interleukin 1 beta likewise, the cognitive deficits were assessed via forced swimming test, gamma-aminobutyric acid, n-methyl-d-aspartate and neuronal nitric oxide synthases besides AMP-activated protein kinase, light chain 3 and caspase3 levels in rats' cerebella.
Key Findings: The obtained results revealed a noticeable improvement in the previously mentioned biochemical factors and behavioral tasks that was reinforced by histopathological examination when using the present remedy.
Significance: metformin and low doses of radiation afforded renoprotection and neuroprotection against cisplatin-induced acute uremic encephalopathy.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
