Hyperlipidemia-Mediated Increased Advanced Lipoxidation End Products Formation, an Important Factor Associated with Decreased Erythrocyte Glucose-6-Phosphate Dehydrogenase Activity in Mild Nonproliferative Diabetic Retinopathy

Choudhuri, Subhadip; Roy, Pijush Kanti; Mitra, Bhaskar; Sen, Susruta; Sarkar, Rajarshi; Das, Mandrita; Biswas, Dibyendu; Ghosh, Pranab; Biswas, Asok; Chakraborty, Shaibal; Mondal, Lakshmi Kanta

doi:10.1016/j.jcjd.2016.07.007

Cited by 12 publications

(11 citation statements)

References 31 publications

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“…Further higher levels of TCH, LDL-C, and TG were found in MNPDR patients compared to DNR. Our results are in conformity with a study by Choudhuri et al. (2017) showing the alteration of TCH, LDL-C, and TG levels among DNR and MNPDR subjects compared to HC.…”

Section: Discussionsupporting

confidence: 93%

Visual contrast sensitivity could be an early marker of diabetic retinopathy

Pramanik

Chowdhury

Ganguly

et al. 2020

Heliyon

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The present study aimed to explore the early predictive marker of diabetic retinopathy (DR) and to elucidate the associated demographic, metabolic, and ocular factors. We enrolled 43 type 2 diabetic subjects with mild non-proliferative retinopathy (MNPDR), 30 diabetic subjects with no retinopathy (DNR), and 35 healthy controls (HC). The study groups showed no significant alteration in central macular thickness (CMT) and visual acuity (VA). The contrast sensitivity (CS) score was found to be significantly lower among DNR and MNPDR subjects compared to HCs (p < 0.0001). Between MNPDR and DNR subjects, the CS score was significantly lower in the former (p = 0.0036). CS score discriminated DNR subjects from HC, with 74% accuracy for the optimal threshold 0.71. The associated area under the ROC curve (AUC) is 0.82 (p < 0.0001) while the discrimination rule has 66% sensitivity and 80% specificity. The CS score also discriminated MNPDR subjects from DNR with 64% accuracy for the optimal threshold 0.53. The associated AUC is 0.65 (p < 0.023) and the rule has 86% sensitivity and 33% specificity. According to best subset regression analysis, not only glycaemic parameters but also lipid parameters [low-density lipoprotein cholesterol (LDL-C) (p = 0.045) and triglycerides (TG) (p = 0.0005)] were found to be significant predictors of CS. CMT (p = 0.058) was another marginally significant predictor of CS. CS may be used as an early predictive marker for DR. So, not only hyperglycemia, but also hyperlipidemia seems to significantly affect retinal CS function in diabetes.

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Section: Discussionsupporting

confidence: 93%

Visual contrast sensitivity could be an early marker of diabetic retinopathy

Pramanik

Chowdhury

Ganguly

et al. 2020

Heliyon

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“…The ALE component like HLY also found to be increased with the pathogenesis and severity of DR in the present study. A previous study by [36] reported a significant elevation of ALE levels among DNR and MNPDR subjects compared to HCs. Moreover, significant elevation of HLY in the vitreous and serum of patients with PDR was also observed by Izuta et al [37], which is following our findings.…”

Section: Discussionmentioning

confidence: 78%

Role of Lipid, Protein-Derived Toxic Molecules, and Deficiency of Antioxidants behind the Pathogenesis of Diabetic Retinopathy (DR) in Type 2 Diabetes Mellitus

Pramanik¹,

Mondal²,

Chowdhury³

et al. 2022

Diabetic Eye Disease - From Therapeutic Pipeline to the Real World

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To determine the role of NADPH-oxidase mediated formation of different lipid, protein-derived molecules, and depletion of vitamin-C level in vitreous behind the endothelial dysfunction-induced vascular endothelial growth factor secretion and pathogenesis of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Fourteen T2DM patients with mild non-proliferative diabetic retinopathy (MNPDR), 11 patients without diabetic retinopathy (DNR), 17 T2 DM subjects with high-risk proliferative diabetic retinopathy (HRPDR), and 5 healthy individuals without DM underwent vitreous analysis for estimation NADPH oxidase, lipid peroxide like malondialdehyde (MDA), 4-Hydroxy-noneal (HNE) and advanced lipoxidation end product (ALE) like Hexanoyl-lysine (HLY), protein carbonyl compound (PCC), Vitamin-C and concentration of vascular endothelial growth factor (VEGF) secretion following standard spectrophotometric methods and enzyme-linked immunosorbent assay (ELISA). Vitreous concentration of NADPH-oxidase, different protein and lipid-derived molecule, and VEGF were found to be significantly elevated among DNR and of DR subjects with different grades compared to HC subjects whereasthe vitamin-C level was found to be decreased among different DR subjects and DNR subjects in comparison to healthy individuals. Oxidative stress-mediated lipid and protein-derived biomolecules not only add important mediators in the pathogenesis of DR, but also accelerate the progression and severity of microangiopathy.

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“…When an antibody-based technique is chosen, the recognition site is crucial. Thus, there are a number of antibodies (monoclonal and polyclonal) that recognized MDA-modified proteins which have been used for immunohistochemistry [ 34 , 35 , 36 ], immunoblot analysis [ 37 , 38 , 39 , 40 , 41 ], two-dimensional PAGE analysis [ 42 ], and ELISA [ 36 , 43 , 44 ]. All these approaches have the limitation that they do not per se provide information about the specific modified protein or the precise site of modification within the protein [ 15 ].…”

Section: Methods To Detect and Quantify Mdalys In Proteinsmentioning

confidence: 99%

“…Likewise, it is remarkable that the higher MDALys concentration is reported in long-lived tissues like brain and heart which, in addition, have higher energy demands, and share identical traits to mitochondria: High lipid content, high degree of unsaturation, and high flux of mitochondrial free radical generation. During the last 30 years, this post-translational modification has also been detected in several pathological models including metabolic diseases such as chronic iron overload [87], metabolic syndrome [88], and type 2 diabetes and its complications [44,52,89,90]; in vascular diseases like atherosclerosis [50,91,92]; and in a diversity of neurodegenerative diseases such as Alzheimer's disease [34,42], Incidental Lewy Body Disease [35], Creutzfeldt-Jakob Disease [93], Pick's disease [38], Lewy Body diseases [48], familial Parkinson's disease [46], and X-adrenoleukodystrophy [94,95]. In all these cases the pathological state presented increased steady-state levels of MDALys ascribed to alteration in lipid profiles and/or oxidative stress.…”

Section: Protein Lipoxidation By Mda In Physiological and Pathological Modelsmentioning

confidence: 99%

The Advanced Lipoxidation End-Product Malondialdehyde-Lysine in Aging and Longevity

et al. 2020

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The nonenzymatic adduction of malondialdehyde (MDA) to the protein amino groups leads to the formation of malondialdehyde-lysine (MDALys). The degree of unsaturation of biological membranes and the intracellular oxidative conditions are the main factors that modulate MDALys formation. The low concentration of this modification in the different cellular components, found in a wide diversity of tissues and animal species, is indicative of the presence of a complex network of cellular protection mechanisms that avoid its cytotoxic effects. In this review, we will focus on the chemistry of this lipoxidation-derived protein modification, the specificity of MDALys formation in proteins, the methodology used for its detection and quantification, the MDA-lipoxidized proteome, the metabolism of MDA-modified proteins, and the detrimental effects of this protein modification. We also propose that MDALys is an indicator of the rate of aging based on findings which demonstrate that (i) MDALys accumulates in tissues with age, (ii) the lower the concentration of MDALys the greater the longevity of the animal species, and (iii) its concentration is attenuated by anti-aging nutritional and pharmacological interventions.

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Hyperlipidemia-Mediated Increased Advanced Lipoxidation End Products Formation, an Important Factor Associated with Decreased Erythrocyte Glucose-6-Phosphate Dehydrogenase Activity in Mild Nonproliferative Diabetic Retinopathy

Cited by 12 publications

References 31 publications

Visual contrast sensitivity could be an early marker of diabetic retinopathy

Visual contrast sensitivity could be an early marker of diabetic retinopathy

Role of Lipid, Protein-Derived Toxic Molecules, and Deficiency of Antioxidants behind the Pathogenesis of Diabetic Retinopathy (DR) in Type 2 Diabetes Mellitus

The Advanced Lipoxidation End-Product Malondialdehyde-Lysine in Aging and Longevity

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