CysLTR1 antagonism by montelukast can ameliorate diabetes-induced aortic and testicular inflammation.
Int Immunopharmacol
; 125(Pt A): 111127, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37907048
ABSTRACT
AIMS:
Montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, is emerging as an attractive strategy to curtail diabetic complications; however, its role in aortic and testicular tissues is unknown. This study investigated the effect of CysLTR1 antagonism by montelukast on toll-like receptor (TLR)4 and nuclear factor kappa B (NF-κB) pathways in diabetes-induced aortic and testicular injury.METHODS:
Adult male Sprague-Dawley rats were made diabetic with Streptozotocin (STZ, 55 mg/kg). Following this, Streptozotocin-induced diabetic (SD) rats were administered montelukast (10 and 20 mg/kg, orally) for 8 weeks. Blood glucose, serum malondialdehyde (MDA), inflammatory markers, and histopathology were evaluated.RESULTS:
Montelukast showed protection against diabetic complications, as evidenced by the ameliorative effect against STZ-induced alterations in oxidative stress as indicated by serum MDA levels. Moreover, montelukast conferred a significant decrease in the aortic and testicular levels of CysLTR1, TLR4, and NF-κB with a subsequent decrease in the levels of NOD-like receptor family pyrin domain containing (NLRP)3, caspase 1, interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α. Additionally, administration of montelukast resulted in autophagy stimulation, as shown by decreased p62/Sequestosome (SQSTM)1 levels. Finally, montelukast protection resulted in normal thickness of whole aortic wall, regular tunica (t.) intima, mild vacuolation of smooth muscle fibers in aorta, increased size of seminiferous tubules, and increased spermatogenesis in testis as demonstrated by histopathology.CONCLUSIONS:
The protective effect of montelukast against diabetes-induced aortic and testicular injury is due to its antioxidant, anti-inflammatory, and autophagy stimulation characteristics.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complicações do Diabetes
/
Diabetes Mellitus
Limite:
Animals
Idioma:
En
Revista:
Int Immunopharmacol
Ano de publicação:
2023
Tipo de documento:
Article