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Therapeutic potential of proteases in acute lung injury and respiratory distress syndrome via TLR4/Nrf2/NF-kB signaling modulation.
Anwar, Hend Mohamed; Salem, Gad Elsayed Mohamed; Abd El-Latief, Hanan M; Osman, Amany Abd Elhameid; Ghanem, Sahar K; Khan, Haroon; Chavanich, Suchana; Darwish, Alshaymaa.
Afiliação
  • Anwar HM; Department of Biochemistry, Egyptian Drug Authority (EDA), Former National Organization for Drug Control and Research (NODCAR), Giza 11221, Egypt.
  • Salem GEM; Reef Biology Research Group, Department of Marine Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • Abd El-Latief HM; Zoology Department, Women's College for Arts, Science and Education, Ain Shams University, Cairo, Egypt.
  • Osman AAE; Zoology Department, Women's College for Arts, Science and Education, Ain Shams University, Cairo, Egypt.
  • Ghanem SK; Pharmacology and Toxicology Department, Faculty of Pharmacy, Sohag University, Egypt.
  • Khan H; Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan. Electronic address: haroonkhan@awkum.edu.pk.
  • Chavanich S; Reef Biology Research Group, Department of Marine Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; Aquatic Resources Research Institute, Chulalongkorn University, Bangkok, Thailand. Electronic address: suchana.c@chula.ac.th.
  • Darwish A; Biochemistry Department, Faculty of Pharmacy, Sohag University, Sohag, Egypt. Electronic address: alshaymaa.Darwish@pharm.sohag.edu.eg.
Int J Biol Macromol ; 267(Pt 1): 131153, 2024 May.
Article em En | MEDLINE | ID: mdl-38574930
ABSTRACT
The COVID-19 pandemic has drawn attention to acute lung injury and respiratory distress syndrome as major causes of death, underscoring the urgent need for effective treatments. Protease enzymes possess a wide range of beneficial effects, including antioxidant, anti-inflammatory, antifibrotic, and fibrinolytic effects. This study aimed to evaluate the potential therapeutic effects of bacterial protease and chymotrypsin in rats in mitigating acute lung injury induced by lipopolysaccharide. Molecular docking was employed to investigate the inhibitory effect of bacterial protease and chymotrypsin on TLR-4, the receptor for lipopolysaccharide. Bacterial protease restored TLR-4, Nrf2, p38 MAPK, NF-kB, and IKK-ß levels to normal levels, while chymotrypsin normalized TLR-4, IKK-ß, IL-6, and IL-17 levels. The expression of TGF-ß, caspase-3, and VEGF in the bacterial protease- and chymotrypsin-treated groups was markedly reduced. Our results suggest that both therapies ameliorate LPS-induced acute lung injury and modulate the TLR4/Nrf2/NF-k signaling pathway. Each protease exhibited distinct mechanisms, with bacterial protease showing a better response to oxidative stress, edema, and fibrosis, whereas chymotrypsin provided a better response in the acute phase and innate immunity. These findings highlight the potential of each protease as a promising therapeutic option for acute lung injury and respiratory distress syndrome.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Transdução de Sinais / Lipopolissacarídeos / NF-kappa B / Fator 2 Relacionado a NF-E2 / Receptor 4 Toll-Like / Lesão Pulmonar Aguda Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Transdução de Sinais / Lipopolissacarídeos / NF-kappa B / Fator 2 Relacionado a NF-E2 / Receptor 4 Toll-Like / Lesão Pulmonar Aguda Idioma: En Ano de publicação: 2024 Tipo de documento: Article