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Angiotensin 1-7 mitigates rhabdomyolysis induced renal injury in rats via modulation of TLR-4/NF-kB/iNOS and Nrf-2/heme­oxygenase-1 signaling pathways.
Abdel-Hakeem, Elshymaa A; Abdel Hafez, Sara Mohamed Naguib; Kamel, Bothina A; Abdel-Hamid, Heba A.
Afiliación
  • Abdel-Hakeem EA; Department of Medical Physiology, Faculty of Medicine, Minia University, 61111 Minia, Egypt. Electronic address: shady@mu.edu.eg.
  • Abdel Hafez SMN; Department of Histology and Cell Biology, Faculty of Medicine, Minia University, 61111 Minia, Egypt.
  • Kamel BA; Department of Biochemistry, Faculty of Medicine, Minia University, 61111 Minia, Egypt.
  • Abdel-Hamid HA; Department of Medical Physiology, Faculty of Medicine, Minia University, 61111 Minia, Egypt.
Life Sci ; 303: 120678, 2022 Aug 15.
Article en En | MEDLINE | ID: mdl-35654118
AIMS: Rhabdomyolysis (RM) is a critical condition with a high mortality rate, but effective management is still deficient. Till date, there are no studies that have addressed the effect of angiotensin 1-7 in this condition, hence, the rationale of this study was to evaluate the potential protective effect of Angiotensin 1-7 (Ang1-7), on rhabdomyolysis (RM) induced kidney injury in rats and detecting the underlying mechanistic insights. MAIN METHODS: Forty adult male albino rats were divided into groups; the control group, RM group, RM+Ang1-7 group, and RM+Ang1-7+ A779 group. Sera and urine samples were collected for analysis of renal and muscle injury markers. Kidney tissues were taken for estimation of oxidative, inflammatory, and apoptotic markers as well as angiotensin-II (Ang II) and Ang1-7. Renal histology and expression of inducible nitric oxide synthase-1 (iNOS), real-time PCR for angiotensin-converting enzyme-2 (ACE-2), nuclear erythroid factor-2 (Nrf-2), Toll like receptor 4 (TLR-4) and NF-kB in kidney tissues were also measured. KEY FINDINGS: Induction of RM caused renal oxidative stress injury, inflammation, apoptosis and marked deterioration in kidney functions as well as reduction of Ang1-7 and raised Angiotensin-II level in kidney tissues. Administration of Ang1-7 to the RM group reversed all the affected parameters which were blocked by A779 administration (Mas receptor blocker). SIGNIFICANCE: We concluded that Ang1-7 could be a potential therapeutic agent that could mitigate RM-induced renal injury. The underlying mechanisms may involve Stimulation of the ACE-2/Ang1-7/MasR axis and modulation of TLR-4/NF-kB/iNOS and Nrf-2/heme­oxygenase -1 pathways.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rabdomiólisis / FN-kappa B Límite: Animals Idioma: En Revista: Life Sci Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rabdomiólisis / FN-kappa B Límite: Animals Idioma: En Revista: Life Sci Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos