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Pioglitazone ameliorates sepsis-associated encephalopathy through SIRT1 signaling pathway.
Shehata, Alaa H; Anter, Aliaa F; Mohamed Naguib Abdel Hafez, Sara; Rn Ibrahim, Ahmed; Kamel, Eman S; Ahmed, Al-Shaimaa F.
Afiliación
  • Shehata AH; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
  • Anter AF; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
  • Mohamed Naguib Abdel Hafez S; Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia, Egypt.
  • Rn Ibrahim A; Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt; Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
  • Kamel ES; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, USA; Department of Clinical Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt.
  • Ahmed AF; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt. Electronic address: Shaimaa.faissal@minia.edu.eg.
Int Immunopharmacol ; 139: 112757, 2024 Sep 30.
Article en En | MEDLINE | ID: mdl-39067401
ABSTRACT
Sepsis is a severe immune response to an infection. It is associated with multiple organ dysfunction syndrome (MODs) along with systemic and neuronal inflammatory response. This study focused on the acute neurologic dysfunction associated with sepsis by exploring the role of PPARγ/SIRT1 pathway against sepsis. We studied the role of this axis in ameliorating sepsis-associated encephalopathy (SAE) and its linked neurobehavioral disorders by using pioglitazone (PIO). This PPARγ agonist showed neuroprotective actions in neuroinflammatory disorders. Sepsis was induced in mice by LPS (10 mg/kg). Survival rate and MODs were assessed. Furthermore, behavioral deficits, cerebral oxidative, inflammatory, and apoptotic markers, and the cerebral expression level of SIRT1 were determined. In this study, we observed that PIO attenuated sepsis-induced cerebral injury. PIO significantly enhanced survival rate, attenuated MODs, and systemic inflammatory response in septic mice. PIO also promoted cerebral SIRT1 expression and reduced cerebral activation of microglia, oxidative stress, HMGB, iNOS, NLRP3 and caspase-3 along with an obvious improvement in behavioral deficits and cerebral pathological damage induced by LPS. Most of the neuroprotective effects of PIO were abolished by EX-527, a SIRT1 inhibitor. These results highlight that the neuroprotective effect of PIO in SAE is mainly SIRT1-dependent.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Lipopolisacáridos / Fármacos Neuroprotectores / Sirtuina 1 / Encefalopatía Asociada a la Sepsis / Pioglitazona Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Lipopolisacáridos / Fármacos Neuroprotectores / Sirtuina 1 / Encefalopatía Asociada a la Sepsis / Pioglitazona Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Países Bajos