Gold Nanoparticle‐Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An <i>In Vivo</i> Study in a Diabetic Animal Model

Ahmad, Saheem; Khan, Mohd Sajid; Alouffi, Sultan; Khan, Saif; Khan, M. Salman; Akasha, Rihab; Faisal, Mohammad; Shahab, Uzma

doi:10.1155/2021/5591851

Cited by 11 publications

(4 citation statements)

References 51 publications

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“…In the past, AGEs inhibitors such as aminoguanidine, pyridoxamine and alagebrium were considered to have renal protective effects. However, due to side effects and other reasons, research has been stagnant [33,34,35]. In our study, the median values of baseline AGEs are similiar in the three diabetic groups, after 12 weeks of SGLT2 inhibitor treatment, AGEs dramatically decreased in three groups compared to baseline.…”

Section: Discussionmentioning

confidence: 46%

SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway

Zeng,

Tian,

Liang

et al. 2023

Preprint

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Aims To estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients. Material and methods 68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR < 30mg/g), T2DM with microalbuminuria group (30 ≤ UACR ≤ 300mg/g), T2DM with macroalbuminuria group (UACR＞300mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), Angiotensin-II (Ang-II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels. Results After 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P < 0.001), respectively. Partial correlations showed that 8-OHdG were highly relevant to the baseline 24-h proteinuria (r = 0.389, p = 0.001), The reduction of OHdG (Δ8-OHdG) were positively correlated with the decrease of proteinuria (Δ24-h proteinuria) after 12 weeks of SGLT2i treatment (r = 0.283, P = 0.031). There was no significant correlation between 24-h proteinuria and AGEs in baseline (r=-0.059, p = 0.640) as well as between ΔAGEs and Δ24-h proteinuria (r = 0.022, p = 0.872) after12 weeks of SGLT2i treatment in T2DM patients. Conclusions SGLT2i may reduce proteinuria in diabetic nephropathy patients, potentially by inhibiting renal tubule oxidative stress, but not through the AGEs pathway and does not induce RAAS activation. Trial registration This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.

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Section: Discussionmentioning

confidence: 46%

SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway

Zeng,

Tian,

Liang

et al. 2023

Preprint

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“…Its high level is found in erythrocytes upon diabetic hyperglycemia [ 27 , 37 ]. The antiglycation activity of HNO was compared with that of aminoguanidine, which is known as an effective AGE scavenger [ 38 , 39 ], and was used as standard antiglycating agent (positive control).…”

Section: Resultsmentioning

confidence: 99%

Antiglycation and Antioxidant Effect of Nitroxyl towards Hemoglobin

et al. 2022

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Donors of nitroxyl and nitroxyl anion (HNO/NO−) are considered to be promising pharmacological treatments with a wide range of applications. Remarkable chemical properties allow nitroxyl to function as a classic antioxidant. We assume that HNO/NO− can level down the non-enzymatic glycation of biomolecules. Since erythrocyte hemoglobin (Hb) is highly susceptible to non-enzymatic glycation, we studied the effect of a nitroxyl donor, Angeli’s salt, on Hb modification with methylglyoxal (MG) and organic peroxide―tert-butyl hydroperoxide (t-BOOH). Nitroxyl dose-dependently decreased the amount of protein carbonyls and advanced glycation end products (AGEs) that were formed in the case of Hb incubation with MG. Likewise, nitroxyl effectively protected Hb against oxidative modification with t-BOOH. It slowed down the destruction of heme, formation of carbonyl derivatives and inter-subunit cross-linking. The protective effect of nitroxyl on Hb in this system is primarily associated with nitrosylation of oxidized Hb and reduction of its ferryl form, which lowers the yield of free radical products. We suppose that the dual (antioxidant and antiglycation) effect of nitroxyl makes its application possible as part of an additional treatment strategy for oxidative and carbonyl stress-associated diseases.

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“…Therefore, AG is an important pre-Amadori inhibitor. AG is toxic at higher concentrations and has been forbidden in human clinical trials [ 100 ]. AG inhibits the development of diabetic complications in animal models of diabetes but does not inhibit the formation of late glycation end products of skin collagen in diabetic rats [ 101 ].…”

Section: Inhibitors Of Agesmentioning

confidence: 99%

Research Advances on the Damage Mechanism of Skin Glycation and Related Inhibitors

Zheng

et al. 2022

Nutrients

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Our skin is an organ with the largest contact area between the human body and the external environment. Skin aging is affected directly by both endogenous factors and exogenous factors (e.g., UV exposure). Skin saccharification, a non-enzymatic reaction between proteins, e.g., dermal collagen and naturally occurring reducing sugars, is one of the basic root causes of endogenous skin aging. During the reaction, a series of complicated glycation products produced at different reaction stages and pathways are usually collectively referred to as advanced glycation end products (AGEs). AGEs cause cellular dysfunction through the modification of intracellular molecules and accumulate in tissues with aging. AGEs are also associated with a variety of age-related diseases, such as diabetes, cardiovascular disease, renal failure (uremia), and Alzheimer’s disease. AGEs accumulate in the skin with age and are amplified through exogenous factors, e.g., ultraviolet radiation, resulting in wrinkles, loss of elasticity, dull yellowing, and other skin problems. This article focuses on the damage mechanism of glucose and its glycation products on the skin by summarizing the biochemical characteristics, compositions, as well as processes of the production and elimination of AGEs. One of the important parts of this article would be to summarize the current AGEs inhibitors to gain insight into the anti-glycation mechanism of the skin and the development of promising natural products with anti-glycation effects.

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Gold Nanoparticle‐Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An In Vivo Study in a Diabetic Animal Model

Cited by 11 publications

References 51 publications

SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway

SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway

Antiglycation and Antioxidant Effect of Nitroxyl towards Hemoglobin

Research Advances on the Damage Mechanism of Skin Glycation and Related Inhibitors

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