Conclusion
ISL can be proposed to be an effective protective therapy to prevent progression of DM-induced vascular injury and to preserve aortic integrity.
Methods
DM was induced in male Sprague-Dawley rats by single I.P. injection of STZ (50 mg/kg). ISL was administrated daily (20 mg/kg, orally) for 8 wks. Key findings: Diabetic group showed a significant aortic injury with evidence of atherosclerotic lesions development. Daily ISL (20 mg/kg, orally) administration for 8 wks significantly restored aortic oxidative/antioxidative stress homeostasis via modulating NrF-2/Keap-1/HO-1. Moreover, ISL treatment restored aortic levels of IL-10 and dampened aortic levels of IL-6 and TNF-α. Caspase-3 expression significantly declined as well. Further, ISL treatment successfully suppressed aortic endothelin-1 (ET-1) expression and restored NO contents, eNOS immunostaining paralleled with retraction in atherosclerotic lesions development, and lipid deposition with histopathological architectural preservation and restoration of almost normal aortic thickness.