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Sitagliptin attenuates cardiomyopathy by modulating the JAK/STAT signaling pathway in experimental diabetic rats.

Al-Rasheed NM, Al-Rasheed NM, Hasan IH, Al-Amin MA, Al-Ajmi HN, Mahmoud AM - Drug Des Devel Ther (2016)

Bottom Line: However, little is known about the involvement of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway modulation in the cardioprotective effects of sitagliptin.The current study aimed to investigate the protective effects of sitagliptin against diabetic cardiomyopathy (DCM), focusing on the modulation of the JAK/STAT pathway.In conclusion, these results confer an evidence that sitagliptin has great therapeutic potential on DCM through down-regulation of the JAK/STAT signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University.

ABSTRACT
Sitagliptin, a dipeptidyl peptidase-4 inhibitor, has been reported to promote cardioprotection in diabetic hearts by limiting hyperglycemia and hyperlipidemia. However, little is known about the involvement of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway modulation in the cardioprotective effects of sitagliptin. The current study aimed to investigate the protective effects of sitagliptin against diabetic cardiomyopathy (DCM), focusing on the modulation of the JAK/STAT pathway. Diabetes was induced by streptozotocin injection, and rats received sitagliptin orally and daily for 90 days. Diabetic rats exhibited hyperglycemia, hyperlipidemia, and a significant increase in heart-to-body weight (HW/BW) ratio. Serum troponin I and creatine kinase MB, cardiac interleukin-6 (IL-6), lipid peroxidation, and nitric oxide levels showed significant increase in diabetic rats. In contrast, both enzymatic and nonenzymatic antioxidant defenses were significantly declined in the heart of diabetic rats. Histopathological study revealed degenerations, increased collagen deposition in the heart of diabetic rats. Sitagliptin alleviated hyperglycemia, hyperlipidemia, HW/BW ratio, histological architecture, oxidative stress, and inflammation, and rejuvenated the antioxidant defenses. In addition, cardiac levels of pJAK2 and pSTAT3 were increased in diabetic rats, an effect which was remarkably decreased after sitagliptin treatment. In conclusion, these results confer an evidence that sitagliptin has great therapeutic potential on DCM through down-regulation of the JAK/STAT signaling pathway.

No MeSH data available.


Related in: MedlinePlus

Effect of sitagliptin on histological changes in the heart of control and diabetic rats.Notes: Photomicrographs of H&E-stained heart sections of (A) control rats; (B) sitagliptin-treated rats showing normal heart tissue with normal features of myocardium cells, blood vessels, and endomysium; (C) diabetic rats revealing focal areas of myocardium degeneration (red arrow) and many myocardium cells degeneration (black arrow); and (D) sitagliptin-treated diabetic rats showing few myocardial cell degenerations (black arrow). Magnification ×400.Abbreviation: H&E, hematoxylin and eosin.
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f5-dddt-10-2095: Effect of sitagliptin on histological changes in the heart of control and diabetic rats.Notes: Photomicrographs of H&E-stained heart sections of (A) control rats; (B) sitagliptin-treated rats showing normal heart tissue with normal features of myocardium cells, blood vessels, and endomysium; (C) diabetic rats revealing focal areas of myocardium degeneration (red arrow) and many myocardium cells degeneration (black arrow); and (D) sitagliptin-treated diabetic rats showing few myocardial cell degenerations (black arrow). Magnification ×400.Abbreviation: H&E, hematoxylin and eosin.

Mentions: Histopathological examination of the H&E-stained heart sections of control rats showed normal heart tissue with normal features of myocardium cells, blood vessels, and endomysium (Figure 5A). Heart sections from sitagliptin-treated rats revealed apparently normal endocardium, myocardium, and endomysium (Figure 5B). On the other hand, sections in the heart of STZ-induced diabetic rats showed focal areas of myocardium degeneration and many myocardium cell degeneration (Figure 5C). Diabetic rats treated with sitagliptin (Figure 5D) showed few myocardial cell degenerations.


Sitagliptin attenuates cardiomyopathy by modulating the JAK/STAT signaling pathway in experimental diabetic rats.

Al-Rasheed NM, Al-Rasheed NM, Hasan IH, Al-Amin MA, Al-Ajmi HN, Mahmoud AM - Drug Des Devel Ther (2016)

Effect of sitagliptin on histological changes in the heart of control and diabetic rats.Notes: Photomicrographs of H&E-stained heart sections of (A) control rats; (B) sitagliptin-treated rats showing normal heart tissue with normal features of myocardium cells, blood vessels, and endomysium; (C) diabetic rats revealing focal areas of myocardium degeneration (red arrow) and many myocardium cells degeneration (black arrow); and (D) sitagliptin-treated diabetic rats showing few myocardial cell degenerations (black arrow). Magnification ×400.Abbreviation: H&E, hematoxylin and eosin.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4933570&req=5

f5-dddt-10-2095: Effect of sitagliptin on histological changes in the heart of control and diabetic rats.Notes: Photomicrographs of H&E-stained heart sections of (A) control rats; (B) sitagliptin-treated rats showing normal heart tissue with normal features of myocardium cells, blood vessels, and endomysium; (C) diabetic rats revealing focal areas of myocardium degeneration (red arrow) and many myocardium cells degeneration (black arrow); and (D) sitagliptin-treated diabetic rats showing few myocardial cell degenerations (black arrow). Magnification ×400.Abbreviation: H&E, hematoxylin and eosin.
Mentions: Histopathological examination of the H&E-stained heart sections of control rats showed normal heart tissue with normal features of myocardium cells, blood vessels, and endomysium (Figure 5A). Heart sections from sitagliptin-treated rats revealed apparently normal endocardium, myocardium, and endomysium (Figure 5B). On the other hand, sections in the heart of STZ-induced diabetic rats showed focal areas of myocardium degeneration and many myocardium cell degeneration (Figure 5C). Diabetic rats treated with sitagliptin (Figure 5D) showed few myocardial cell degenerations.

Bottom Line: However, little is known about the involvement of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway modulation in the cardioprotective effects of sitagliptin.The current study aimed to investigate the protective effects of sitagliptin against diabetic cardiomyopathy (DCM), focusing on the modulation of the JAK/STAT pathway.In conclusion, these results confer an evidence that sitagliptin has great therapeutic potential on DCM through down-regulation of the JAK/STAT signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University.

ABSTRACT
Sitagliptin, a dipeptidyl peptidase-4 inhibitor, has been reported to promote cardioprotection in diabetic hearts by limiting hyperglycemia and hyperlipidemia. However, little is known about the involvement of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway modulation in the cardioprotective effects of sitagliptin. The current study aimed to investigate the protective effects of sitagliptin against diabetic cardiomyopathy (DCM), focusing on the modulation of the JAK/STAT pathway. Diabetes was induced by streptozotocin injection, and rats received sitagliptin orally and daily for 90 days. Diabetic rats exhibited hyperglycemia, hyperlipidemia, and a significant increase in heart-to-body weight (HW/BW) ratio. Serum troponin I and creatine kinase MB, cardiac interleukin-6 (IL-6), lipid peroxidation, and nitric oxide levels showed significant increase in diabetic rats. In contrast, both enzymatic and nonenzymatic antioxidant defenses were significantly declined in the heart of diabetic rats. Histopathological study revealed degenerations, increased collagen deposition in the heart of diabetic rats. Sitagliptin alleviated hyperglycemia, hyperlipidemia, HW/BW ratio, histological architecture, oxidative stress, and inflammation, and rejuvenated the antioxidant defenses. In addition, cardiac levels of pJAK2 and pSTAT3 were increased in diabetic rats, an effect which was remarkably decreased after sitagliptin treatment. In conclusion, these results confer an evidence that sitagliptin has great therapeutic potential on DCM through down-regulation of the JAK/STAT signaling pathway.

No MeSH data available.


Related in: MedlinePlus