Ameliorative effect of lixisenatide on diabetic cardiovascular damage and its enhancement via ticagrelor co-administration in rats: possible role of eNOS and NrF2 /HO-1 signaling.
Pharmazie
; 79(6): 101-108, 2024 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-38877681
ABSTRACT
In this study, we hypothesized that lixisenatide (LIX) and ticagrelor (TIC) could have a protective effect against type 2 diabetes mellitus (T2DM)-induced vascular damage. Furthermore, we explored the possible additional protective effect of co-administering LIX and TIC in the treatment regimen. Methods:
50 male rats were divided into five groups, each comprising 10 rats C (control), D (T2DM rats), D + LIX (T2DM rats treated with LIX for 4 weeks), D + TIC (T2DM rats treated with TIC for 4 weeks), and D + LIX + TIC (T2DM rats treated with LIX + TIC for 4 weeks).Results:
The D group showed an increase in body weight, blood glucose, hemostatic model assessment for insulin resistance (HOMA-IR), aorta reactive oxygen species (ROS), and nuclear factor kappa B (NF-κ B), along with a reduction in serum insulin, aorta superoxide dismutase (SOD), glutathione reduced (GSH), nuclear factor erythroid-2 (NrF2), hemeoxygenase-1 (HO-1), and endothelial nitric oxide synthase (eNOS). Deterioration in the aorta histopathological condition, coupled with a noticeable impairment in vascular reactivity compared to the C group, was observed. A single administration of LIX showed a reduction in body weight, blood glucose, HOMA-IR, aorta ROS, and NF-κ B, accompanied by an increase in serum insulin, aorta SOD, GSH, NrF2, HO-1, and eNOS. Amelioration in the aorta histopathological condition and improved vascular reactivity compared to the D group were reported. Similarly, a single administration of TIC showed a reduction in aorta ROS and NF-κ B, along with an increase in aorta SOD, GSH, NrF2, HO-1, and eNOS. A slight amelioration was detected in the aorta histopathological condition, with improved vascular reactivity compared to the D group. The combined administration of LIX and TIC showed a reduction in aorta ROS and NF-κ B, along with an increase in aorta GSH, SOD, HO-1, and eNOS. This was combined with evident amelioration in the aorta histopathological condition and noticeable improvement in vascular reactivity compared to the single treatment with either LIX or TIC group.Conclusion:
The present study introduces clear evidence that the administration of LIX and TIC can improve metabolic and vascular complications of T2DM through modulating eNOS and NrF2 /HO-1 signaling. The combined administration of LIX and TIC produced more significant effects than a single treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Signal Transduction
/
Reactive Oxygen Species
/
Diabetes Mellitus, Experimental
/
Nitric Oxide Synthase Type III
/
NF-E2-Related Factor 2
/
Ticagrelor
Limits:
Animals
Language:
En
Journal:
Pharmazie
Journal subject:
FARMACIA
Year:
2024
Document type:
Article