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Objectives: Diabetic cardiomyopathy is a known complication of diabetes mellitus. Herein, we aimed to determine whether glycemic control mediated by sitagliptin, a dipeptidyl peptidase-4 inhibitor, can ameliorate diabetic myocardial abnormalities by modulating TGF-β signaling via the SMAD and integrin-linked kinase (ILK) pathways. Methods: Four groups of male Wistar albino rats were used, with six rats in each group. Two nondiabetic and two diabetic (produced by a single intraperitoneal dose of streptozotocin (55 mg/kg)) groups were administered either normal saline or sitagliptin (100 mg/kg) orally for 6 weeks. Subsequently, HW/BW ratios and cardiac enzymes were assessed, along with a histological examination of cardiac tissues. Levels of TGF-β, collagen I, p-SMAD2/3, TNF-α, MMP-9, and ILK were detected. Results: Compared with the diabetic control group, sitagliptin-treated diabetic rats exhibited considerably reduced HW/BW ratios and troponin I and creatine kinase-MB levels, with improvements in histopathological changes in cardiac tissues. TGF-β, collagen I, p-SMAD2/3, TNF-α, and MMP-9 levels were significantly decreased in the sitagliptin-treated diabetic group, whereas ILK was elevated following sitagliptin treatment. Conclusion: Sitagliptin could afford cardioprotective effects for the first time by altering ILK-associated TGF-β/SMAD signaling pathways. Thus, sitagliptin may be a promising therapeutic target for the prevention of diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury. Rats were allocated into four groups: two nondiabetic groups, control rats and ST rats (100 mg/kg), and two diabetic groups induced by STZ, and they received either normal saline or ST for 90 days. Diabetic rats showed significant hyperglycemia, hyperlipidemia, and elevation in liver enzymes. After STZ induction, the results revealed remarkable increases in hepatic oxidative stress, inflammation, and hepatocyte degeneration. In addition, STZ upregulated the immunoreactivity of NF-κB/p65, NLRP3, and mTOR but downregulated IKB-α in liver tissue. The use of ST mitigated metabolic and hepatic changes induced by STZ; it also reduced oxidative stress, inflammation, and hepatocyte degeneration. The normal expression of NF-κB/p65, NLRP3, mTOR, and IKB-α were restored with ST treatment. Based on that, our study revealed for the first time the hepatoprotective effect of ST that is mediated by controlling inflammation, oxidative stress, and mTOR/NF-κB/NLRP3 signaling. [ABSTRACT FROM AUTHOR]

Isoproterenol (ISO), a chemically synthesized catecholamine, belongs to β-adrenoceptor agonist used to treat bradycardia. The β-adrenergic agonist is an essential regulator of myocardial metabolism and contractility; however, excessive exposure to ISO can initiate oxidative stress and inflammation. This study aims to investigate the molecular mechanisms underlying ISO-induced cardiac remodeling, the protective efficacy of resveratrol (RSVR), and its liposomal formulation (L-RSVR) against such cardiac change. Wistar albino rats were evenly divided into 4 groups. Control group, ISO group received ISO (50 mg/kg, s.c.) twice a week for 2 weeks, and RSVR- and L-RSVR-treated groups in which rats received either RSVR or L-RSVR (20 mg/kg/day, p.o.) along with ISO for 2 weeks. ISO caused a significant elevation of the expression levels of BAX and MEF2 mRNA, S100A1 and cytochrome C proteins, as well as DNA fragmentation in cardiac tissue compared to the control group. Treatment with either RSVR or L-RSVR for 14 days significantly ameliorated the damage induced by ISO, as evidenced by the improvement of all measured parameters. The present study shows that L-RSVR provides better cardio-protection against ISO-induced cardiac injury in rats, most likely through modulation of cardiac S100A1 protein expression and inhibition of inflammation and apoptosis. [ABSTRACT FROM AUTHOR]