Alleviation of albumin glycation-induced diabetic cardiomyopathy by L-Arginine: Insights into Nrf-2 signaling.

In hyperglycemia, accelerated glycation and oxidative stress give rise to many diabetic complications, such as diabetic cardiomyopathy (DCM). Glycated human serum albumin (GHSA) has disturbed structural integrity and hampered functional capabilities. When GHSA accumulates around cardiac cells, Nrf-2 is dysregulated, aiding oxidative stress. L-Arginine (L-Arg) is prescribed to patients with diabetes and cardiovascular diseases. This research contributes to the mechanistic insights on antiglycation and antioxidant potential of L-Arg in alleviating DCM. HSA was glycated with methylglyoxal in the presence of L-Arg (20-640 mM). Structural and functional modifications of HSA were studied. L-Arg and HSA, GHSA interactions, and thermodynamics were determined by steady-state fluorescence. H9c2 cardiomyocytes were given treatments of GHSA-L-Arg along with the inhibitor of the receptor of AGEs. Cellular antioxidant levels, detoxification enzyme activities were measured. Gene, protein expressions, and immunofluorescence data examined the activation and nuclear translocation of Nrf-2 during glycation and oxidative stress. L-Arg protected HSA from glycation-induced structural and functional modifications. The binding affinity of L-Arg was more towards HSA (104 M-1). L-Arg, specifically at lower concentration (20 mM), upregulated Nrf-2 gene, protein expressions and facilitated its nuclear translocation by activating Nrf-2 signaling. The study concluded that L-Arg can be of therapeutic advantage in glycation-induced DCM and associated oxidative stress.

Protective effect of colchicine on albumin glycation and cellular oxidative stress: Insights into diabetic cardiomyopathy.

The present work elucidates the role of colchicine (COL) on albumin glycation and cellular oxidative stress in diabetic cardiomyopathy (DCM). Human serum albumin (HSA) was glycated with methylglyoxal in the presence of COL (2.5, 3.75, and 5 µM), whereas positive and negative control samples were maintained separately. The effects of COL on HSA glycation, structural and functional modifications in glycated HSA were analyzed using different spectroscopical and fluorescence techniques. Increased fructosamine, carbonyl, and pentosidine formation in glycated HSA samples were inhibited in the presence of COL. Structural conformation of HSA and glycated HSA samples was examined by field emission scanning electron microscopy, circular dichroism, Fourier transform infrared, and proton nuclear magnetic resonance analyses, where COL maintained both secondary and tertiary structures of HSA against glycation. Functional marker assays included ABTS•+ radical scavenging and total antioxidant activities, advanced oxidative protein product formation, and turbidimetry, which showed preserved functional properties of glycated HSA in COL-containing samples. Afterward, rat cardiomyoblast (H9c2 cell line) was treated with glycated HSA-COL complex (400 µg/mL) for examining various cellular antioxidants (nitric oxide, catalase, superoxide dismutase, and glutathione) and detoxification enzymes (aldose reductase, glyoxalase I, and II) levels. All three concentrations of COL exhibited effective anti-glycation properties, enhanced cellular antioxidant levels, and detoxification enzyme activities. The report comprehensively analyzes the potential anti-glycation and properties of COL during its initial assessment.

Lipoxin and glycation in SREBP signaling: Insight into diabetic cardiomyopathy and associated lipotoxicity.

Diabetes and cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Diabetes increases cardiovascular risk through hyperglycemia and atherosclerosis. Chronic hyperglycemia accelerates glycation reaction, which forms advanced glycation end products (AGEs). Additionally, hyperglycemia with enhanced levels of cholesterol, native and oxidized low-density lipoproteins, free fatty acids, and oxidative stress induces lipotoxicity. Accelerated glycation and disturbed lipid metabolism are characteristic features of diabetic heart failure. SREBP signaling plays a significant role in lipid and glucose homeostasis. AGEs increase lipotoxicity in diabetic cardiomyopathy by inhibiting SREBP signaling. While anti-inflammatory lipid mediators, lipoxins resolve inflammation caused by lipotoxicity by upregulating the PPARγ expression and regulating CD36. PPARγ connects the bridge between glycation and lipoxin in SREBP signaling. A summary of treatment modalities against diabetic cardiomyopathy is given in brief. This review indicates the novel therapeutic approach in the crosstalk between glycation and lipoxin in SREBP signaling.