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Atherosclerosis has been linked to chronic inflammatory processes. Changes in the levels of lipoproteins, especially low-density lipoprotein or its variants, as well as inflammatory markers are risk factors for the atherosclerosis. In the present study, an experimental model of rheumatoid arthritis was developed by administrating collagen suspension intradermally in the tail region of Wistar albino rats. At the same time, a suspension of hesperidin (50 mg/kg body weight) and daidzein (20 mg/kg body weight) was orally administrated. The compounds were given in the morning and evening for 21 days. Levels of inflammatory markers in the homogenate of knee joints of experimental rats as well as plasma lipoproteins were investigated. The administration of hesperidin and daidzein caused significant (p < 0.001) decrease in articular elastase activity, TNF-α, and malondialdehyde levels. Further, arthritis scoring and histological findings supported the anti-inflammatory actions of the test compounds. Interestingly, the test compounds also lowered the plasma low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglyceride but increased the level of high-density lipoprotein cholesterol. The test compounds thus ameliorated the risk factors of atherosclerosis. Furthermore, antioxidant roles of hesperidin as well as daidzein were evident from decrease in free radical load demonstrated as increase in total antioxidant level in plasma of arthritic animals treated with hesperidin and daidzein. In a separate in vitro experiment, enhanced free radical scavenging activity of hesperidin was demonstrated against 2,2-diphenyl-1-picrylhydrazyl and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid. The anti-inflammatory, hypolipidemic, and antioxidant actions of the naturally occurring test compounds, particularly hesperidin, seem to be quite effective against rheumatoid arthritis and atherosclerosis. Thus, their consumption may be helpful in prevention or at least delaying the onset of these diseases in susceptible individuals.

Carbamylation (or carbamoylation) is a non-enzymatic modification of biomolecules mediated by cyanate, a dissociation product of urea. Proteins are more sensitive to carbamylation. Two major sites of carbamylation reaction are: N -amino moiety of a protein N-terminus and the N -amino moiety of proteins' lysine residues. In kidney diseases, urea accumulates and the burden of carbamylation increases. This may lead to alteration in the structure and function of many important proteins relevant in maintenance of homeostasis. Carbamylated proteins namely, carbamylated-haemoglobin and carbamylated-low density lipoprotein (LDL) have been implicated in hypoxia and atherosclerosis, respectively. Furthermore, carbamylation of insulin, oxytocin, and erythropoietin have caused changes in the action of these hormones vis-à-vis the metabolic pathways they control. In this short review, authors have compiled the data on role of carbamylated proteins, enzymes, hormones, LDL, and so on, in human diseases. © 2018 IUBMB Life, 70(4):267-275, 2018.

Structural and functional changes in albumin are of particular interest as numerous studies in vivo have reported a strong involvement of glycated-HSA in the development and progression of chronic diabetic complications. Non-enzymatic addition of glucose molecules to a protein induces structural changes in it. These changes depend on the degree of glycation. In this study, conformational changes in glycated-HSA and its antioxidant capacity were evaluated. HSA was purified from diabetic patients with/without CKD and healthy subjects. Glycation induced an increase in the molecular mass of HSA as determined by mass spectroscopy. Further secondary and tertiary structural changes were observed by UV, circular dichroism (CD) spectroscopy, Fourier transform infrared spectroscopy (FTIR), tryptophan and 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence. The mean α-helix content was found to be 59.46% for normal HSA and it was reduced down to 45.63% in HSA isolated from diabetic patients without CKD and to 37.48% in CKD-HSA. FTIR analysis showed Amide I and Amide II band shifting in HSA of diabetic patients without and with CKD. These findings indicate the secondary structure changes in glycated HSA. The tertiary structure is also affected by in vivo glycation as confirmed by intrinsic fluorescence and ANS fluorescence results. Consequently, these structural changes associated with glycation provoked a reduction in the free thiol group and a strong increment of protein carbonyl contents and the fructosamine level in glycated HSA. Antioxidant activity was evaluated by a RBC hemolysis test. The result indicates that the free radical scavenging capacities of HSA were decreased in diabetic patients with or without CKD. Our study revealed that structural and functional features of glycated HSA, isolated from diabetic patients with and without CKD were significantly different from the HSA isolated from non-diabetic subjects. Moreover these changes were more prominent in HSA isolated from diabetic patients with CKD. These findings suggest that active sites of HSA may not be available under extensive glycation, leading to the impairment of its important functions. Thus glycated HSA may be involved in the pathogenesis of diabetes and its complications such as chronic kidney disease.