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The newly synthesized compounds (NCHDH and NTHDH) attenuates LPS-induced septicemia and multi-organ failure via Nrf2/HO1 and HSP/TRVP1 signaling in mice.
Khan, Ashraf Ullah; Muhammad Khan, Amir; Khan, Adnan; Shal, Bushra; Aziz, Abdul; Ahmed, Muhammad Naeem; Khan, Salman.
Afiliação
  • Khan AU; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
  • Muhammad Khan A; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
  • Khan A; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
  • Shal B; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
  • Aziz A; Department of Chemistry, The University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan.
  • Ahmed MN; Department of Chemistry, The University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan.
  • Khan S; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: skhan@qau.edu.pk.
Chem Biol Interact ; 329: 109220, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32763245
ABSTRACT
The sepsis is considered as serious clinic-pathological condition related with high rate of morbidity and mortality in critical care settings. In the proposed study, the hydrazides derivatives N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (1-2) (NCHDH and NTHDH) were investigated against the LPS-induced sepsis in rodents. The NCHDH and NTHDH markedly improved the physiological sign and symptoms associated with the sepsis such as mortality, temperature, and clinical scoring compared to negative control group, which received only LPS (i.p.). The NCHDH and NTHDH also inhibited the production of the NO and MPO compared to the negative control. Furthermore, the treatment control improved the histological changes markedly of all the vital organs. Additionally, the Masson's trichrome and PAS (Periodic Acid Schiff) staining also showed improvement in the NCHDH and NTHDH treated group in contrast to LPS-induced group. The antioxidants were enhanced by the intervention of the NCHDH and NTHDH and the level of the MDA and POD were attenuated marginally compared to the LPS-induced group. The hematology study showed marked improvement and the reversal of the LPS-induced changes in blood composition compared to the negative control. The synthetic function of the liver and kidney were preserved in the NCHDH and NTHDH treated group compared to the LPS-induced group. The NCHDH and NTHDH markedly enhanced the Nrf2, HO-1 (Heme oxygenase-1), while attenuated the Keap1 and TRPV1 expression level as compared to LPS treated group. Furthermore, the NCHDH and NTHDH treatment showed marked increased in the mRNA expression level of the HSP70/90 proteins compared to the negative control.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Sepse / Hidrazinas / Insuficiência de Múltiplos Órgãos Tipo de estudo: Estudo observacional Limite: Animais Idioma: Inglês Revista: Chem Biol Interact Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Paquistão

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Sepse / Hidrazinas / Insuficiência de Múltiplos Órgãos Tipo de estudo: Estudo observacional Limite: Animais Idioma: Inglês Revista: Chem Biol Interact Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Paquistão
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