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G protein-coupled estrogen receptor selective agonist, G1, improves the molecular and biochemical markers in a cisplatin mouse model of CKD.
Ahmed, Hala A; Shaaban, Ahmed A; Makled, Mirhan N; Ibrahim, Tarek M.
Afiliación
  • Ahmed HA; Pharmacology and Biochemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Egypt; Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt.
  • Shaaban AA; Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt; Faculty of Pharmacy, Jerash University, Jerash, 26150, Jordan.
  • Makled MN; Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt. Electronic address: Mirhan_makled@hotmail.com.
  • Ibrahim TM; Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt.
Chem Biol Interact ; 398: 111065, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-38795875
ABSTRACT
Multiple cycles of cisplatin result in a permanent loss of kidney function with severe and life-limited chronic kidney disease (CKD) after successful cisplatin therapy. Recently, studies have showed that the activation of G-protein coupled estrogen receptor (GPER) could protect against kidney disease. This study aimed to test the potential of the G1 compound, a GPER selective agonist, to prevent CKD development after cisplatin therapy. Male C57BL/6 mice were exposed to 2 cycles of 2.5 mg/kg cisplatin in a regimen miming clinical exposure (1 injection daily for 5 days, followed by a 16-day recovery period between cycles). G1 (50 or 100 µg/kg) was administered daily for 6 weeks. G1 dose-dependently improved kidney function biomarkers (serum creatinine, creatinine clearance, and protein excretion) and histopathological changes compared to the cisplatin-treated group. Collagen 3 expression was dose-dependently decreased in G1-treated groups that was parallel to the reduction of fibrosis in Masson's trichrome-stained sections. G1 administration also increased total antioxidant capacity (TAC) and nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced the level of malondialdehyde and the proinflammatory cytokine, tumor necrosis factor-α. In addition, G1 downregulated the expression of inflammasome NLRP3 and nuclear factor kappa B p65 (NF-κB p65) in a dose-dependent manner. In conclusion, these data suggest that G1 could be a new therapeutic tool for CKD prevention post cisplatin therapy. These effects might be mediated through the activation of Nrf2 and the inhibition of NF-κB/NLRP3 signaling.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Receptores Acoplados a Proteínas G / Modelos Animales de Enfermedad / Insuficiencia Renal Crónica / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Receptores Acoplados a Proteínas G / Modelos Animales de Enfermedad / Insuficiencia Renal Crónica / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Irlanda