Advanced glycation end products and diabetic nephropathy: a comparative study using diabetic and normal rats with methylglyoxal-induced glycation

Rodrigues, Lisa; Matafome, Paulo; Crisóstomo, Joana; Santos-Silva, Daniela; Sena, Cristina M.; Pereira, Paulo; Seiça, Raquel

doi:10.1007/s13105-013-0291-2

Cited by 33 publications

(27 citation statements)

References 27 publications

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“…Consistent with in vitro data, alterations of podocyte adhesion to the basal membrane were observed in diabetic rats, due to the loss of integrin function, as well as tubulointerstitial fibrosis . Our group has recently compared the effects of dietary MG supplementation with diabetic rats and observed similar glomerular effects of MG with the endogenous lesions of diabetic rats . Accordingly, decreased kidney GLO1 expression and increased MG formation during ischemia–reperfusion were observed to result in tubulointerstitial lesions.…”

Section: Pathophysiological Relevance Of Methylglyoxal In Metabolic Dsupporting

confidence: 81%

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

Matafome

Rodrigues

Sena

et al. 2016

Medicinal Research Reviews

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Glucose and fructose metabolism originates the highly reactive byproduct methylglyoxal (MG), which is a strong precursor of advanced glycation end products (AGE). The MG has been implicated in classical diabetic complications such as retinopathy, nephropathy, and neuropathy, but has also been recently associated with cardiovascular diseases and central nervous system disorders such as cerebrovascular diseases and dementia. Recent studies even suggested its involvement in insulin resistance and beta-cell dysfunction, contributing to the early development of type 2 diabetes and creating a vicious circle between glycation and hyperglycemia. Despite several drugs and natural compounds have been identified in the last years in order to scavenge MG and inhibit AGE formation, we are still far from having an effective strategy to prevent MG-induced mechanisms. This review summarizes the endogenous and exogenous sources of MG, also addressing the current controversy about the importance of exogenous MG sources. The mechanisms by which MG changes cell behavior and its involvement in type 2 diabetes development and complications and the pathophysiological implication are also summarized. Particular emphasis will be given to pathophysiological relevance of studies using higher MG doses, which may have produced biased results. Finally, we also overview the current knowledge about detoxification strategies, including modulation of endogenous enzymatic systems and exogenous compounds able to inhibit MG effects on biological systems.

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Section: Pathophysiological Relevance Of Methylglyoxal In Metabolic Dsupporting

confidence: 81%

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

Matafome

Rodrigues

Sena

et al. 2016

Medicinal Research Reviews

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“…In vivo, it has recently been demonstrated that long-term MGO administration (14 weeks) to normal rats leads to structural changes in the adipose tissue microvasculature, hypoadiponectinaemia and lipolysis. These effects are associated with increased tissue glycation and impaired expression of apoptotic and angiogenic markers, but not with insulin resistance [174,175]. In contrast, shortterm MGO administration (8 weeks) causes much less severe effects, despite the fact that tissue accumulation of CEL takes place [176,177].…”

Section: Obesitymentioning

confidence: 99%

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

2015

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The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

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“…Glyoxal is a product of cellular peroxidation and protein glycation. Advanced glycation endproducts (AGEs) are associated with the progression of diabetic nephropathy and increased pro-inflammatory cytokines such as IL-1β, which can both be ameliorated by methylglyoxal trapping [16, 17, 18, 19]. Also, diabetics tend to excrete more oxalate than healthy individuals [20, 21, 22].…”

Section: Oxalate – Endogenous Productionmentioning

confidence: 99%

Oxalate, inflammasome, and progression of kidney disease

Ermer

Eckardt²,

Aronson³

et al. 2016

Current Opinion in Nephrology and Hypertension

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Purpose of review Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis and progressive renal failure. It has long been known that as glomerular filtration rate (GFR) becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary etiology. Recent findings The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the nucleotide-binding domain, leucine-rich repeat inflammasome 3 (also known as NALP3, NLRP3 or cryopyrin), resulting in release of Interleukin-1β and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure. Summary The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials.

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Advanced glycation end products and diabetic nephropathy: a comparative study using diabetic and normal rats with methylglyoxal-induced glycation

Cited by 33 publications

References 27 publications

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

Oxalate, inflammasome, and progression of kidney disease

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