The pyridoxamine action on Amadori compounds: A reexamination of its scavenging capacity and chelating effect

Adrover, Miquel; Vilanova, Bartolomé; Frau, Juan; Muñoz, Francisco; Donoso, Josefa

doi:10.1016/j.bmc.2008.04.002

Cited by 50 publications

(35 citation statements)

References 72 publications

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“…Second, by removing toxic carbonyl products derived from both glucose and lipids such as glyoxal and methylglyoxal (MG). Third, by sequestering reactive oxygen species [33], [41]. A variety of preclinical studies indicate that PYR improves kidney structure and function and has been tested for clinical utility in the treatment of diabetic nephropathy [42].…”

Section: Discussionmentioning

confidence: 99%

Combined Anti-Inflammatory and Anti-AGE Drug Treatments Have a Protective Effect on Intervertebral Discs in Mice with Diabetes

et al. 2013

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ObjectiveDiabetes and low back pain are debilitating diseases and modern epidemics. Diabetes and obesity are also highly correlated with intervertebral disc (IVD) degeneration and back pain. Advanced-glycation-end-products (AGEs) increase reactive-oxygen-species (ROS) and inflammation, and are one cause for early development of diabetes mellitus. We hypothesize that diabetes results in accumulation of AGEs in spines and associated spinal pathology via increased catabolism. We present a mouse model showing that: 1) diabetes induces pathological changes to structure and composition of IVDs and vertebrae; 2) diabetes is associated with accumulation of AGEs, TNFα, and increased catabolism spinal structures; and 3) oral-treatments with a combination of anti-inflammatory and anti-AGE drugs mitigate these diabetes-induced degenerative changes to the spine.MethodsThree age-matched groups of ROP-Os mice were compared: non-diabetic, diabetic (streptozotocin (STZ)-induced), or diabetic mice treated with pentosan-polysulfate (anti-inflammatory) and pyridoxamine (AGE-inhibitor). Mice were euthanized and vertebra-IVD segments were analyzed by μCT, histology and Immunohistochemistry.ResultsDiabetic mice exhibited several pathological changes including loss in IVD height, decreased vertebral bone mass, decreased glycosaminoglycan content and morphologically altered IVDs with focal deposition of tissues highly expressing TNFα, MMP-13 and ADAMTS-5. Accumulation of larger amounts of methylglyoxal suggested that AGE accumulation was associated with these diabetic degenerative changes. However, treatment prevented or reduced these pathological effects on vertebrae and IVD.ConclusionThis is the first study to demonstrate specific degenerative changes to nucleus pulposus (NP) morphology and their association with AGE accumulation in a diabetic mouse model. Furthermore, this is the first study to demonstrate that oral-treatments can inhibit AGE-induced ROS and inflammation in spinal structures and provide a potential treatment to slow progression of degenerative spine changes in diabetes. Since diabetes, IVD degeneration, and accumulation of AGEs are frequent consequences of aging, early treatments to reduce AGE-induced ROS and Inflammation may have broad public-health implications.

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Section: Discussionmentioning

confidence: 99%

Combined Anti-Inflammatory and Anti-AGE Drug Treatments Have a Protective Effect on Intervertebral Discs in Mice with Diabetes

et al. 2013

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“…It is reported as a potential drug candidate against protein glycation via multiple mechanisms such as reacting with Amadori compounds that act as precursors of AGEs, and chelating metal ions that catalyze Amadori reactions [110]. Pyrodoxamine has also been well known as a scavenger of several aldehydes generated from lipid peroxidation including MDA, GO and glycolaldehyde (GLA) [111].…”

Section: Impact On Healthmentioning

confidence: 99%

Acrolein scavengers: Reactivity, mechanism and impact on health

Zhu

Sun

Jiang

et al. 2011

Molecular Nutrition Food Res

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Acrolein (ACR) is an α,β-unsaturated aldehyde that exists extensively in the environment and (thermally processed) foods. It can also be generated through endogenous metabolism. Its high electrophilicity makes this aldehyde notorious for its facile reaction with biological nucleophiles, leading to the modification of proteins/DNA and depletion of glutathione. Recent studies also have revealed its roles in disturbing various cell signing pathways in biological systems. With growing evidences of ACR's implication in human diseases, strategies to eliminate its hazardous impacts are of great importance. One of the intervention strategies is the application of reactive scavengers to directly trap ACR. Some known ACR scavengers include sulfur (thiol)-containing and nitrogen (amino)-containing compounds as well as the newly emerging natural polyphenols. In this review, the interactions between ACR and its scavengers are highlighted. The discussion about ACR scavengers is mainly focused on their chemical reactivity, trapping mechanisms as well as their roles extended to biological relevance. In addition to their direct trapping effect on ACR, these scavengers might possess multiple functions and offer additional benefits against ACR-induced toxicity. A comprehensive understanding of the mechanism involved may help to establish ACR scavenging as a novel therapeutic intervention against human diseases that are associated with ACR and/or oxidative stress.

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“…This compound was not approved by the US Food and Drug Administration due to adverse side effects in diabetic patients during Phase III clinical trials, and the search for safer alternatives continues. Pyridoxamine (Vitamin B6, Pyridorin) and thiamin pyrophosphate are potential alternatives to aminoguanidine, as the former suppresses the formation CML [94–96]. Furthermore, these compounds are also good metal ion chelators and attenuate oxidative stress.…”

Section: Antioxidant Therapy In Alzheimer’s Disease and Diabetesmentioning

confidence: 99%

Oxidative Stress in Diabetes and Alzheimer's Disease

Reddy

Zhu

Perry

et al. 2009

JAD

240

145

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Oxidative stress plays a major role in diabetes as well as in Alzheimer's disease and other related neurological diseases. Intracellular oxidative stress arises due to the imbalance in the production of reactive oxygen/reactive nitrogen species and cellular antioxidant defense mechanisms. In turn, the excess reactive oxygen/reactive nitrogen species mediate the damage of proteins and nucleic acids, which have been shown to have direct and deleterious consequences in diabetes and Alzheimer's disease. Oxidative stress also contributes to the production of advanced glycation end products through glycoxidation and lipid peroxidation. The advanced glycation end products and lipid peroxidation products are ubiquitous to diabetes and Alzheimer's disease and serve as markers of disease progression in both disorders. Antioxidants and advanced glycation end products inhibitors, either induced endogenously or exogenously introduced, may counteract with the deleterious effects of the reactive oxygen/reactive nitrogen species and thereby, in prevention or treatment paradigms, attenuate or substantially delay the onset of these devastating pathologies.

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The pyridoxamine action on Amadori compounds: A reexamination of its scavenging capacity and chelating effect

Cited by 50 publications

References 72 publications

Combined Anti-Inflammatory and Anti-AGE Drug Treatments Have a Protective Effect on Intervertebral Discs in Mice with Diabetes

Combined Anti-Inflammatory and Anti-AGE Drug Treatments Have a Protective Effect on Intervertebral Discs in Mice with Diabetes

Acrolein scavengers: Reactivity, mechanism and impact on health

Oxidative Stress in Diabetes and Alzheimer's Disease

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