The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons

Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diab...

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Main Authors: Cezary Watala, Kamil Karolczak, Karolina Siewiera, Magdalena Labieniec-Watala
Format: Article
Language:English
Published: MDPI AG 2013-11-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/18/11/13769
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author Cezary Watala
Kamil Karolczak
Karolina Siewiera
Magdalena Labieniec-Watala
author_facet Cezary Watala
Kamil Karolczak
Karolina Siewiera
Magdalena Labieniec-Watala
author_sort Cezary Watala
collection DOAJ
description Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amido)amine (PAMAM) dendrimers (G2, G3 and G4) have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer’s disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia.
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spelling doaj.art-3221b76ed1f849bdaa194ed9969db60a2022-12-21T19:27:58ZengMDPI AGMolecules1420-30492013-11-011811137691381110.3390/molecules181113769The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and ConsCezary WatalaKamil KarolczakKarolina SiewieraMagdalena Labieniec-WatalaDiabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amido)amine (PAMAM) dendrimers (G2, G3 and G4) have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer’s disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia.http://www.mdpi.com/1420-3049/18/11/13769PAMAM dendrimersdiabetes mellitushyperglycaemiamitochondria functionbioenergeticsnon-enzymatic glycosylationdiabetic markersin vivo study
spellingShingle Cezary Watala
Kamil Karolczak
Karolina Siewiera
Magdalena Labieniec-Watala
The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons
Molecules
PAMAM dendrimers
diabetes mellitus
hyperglycaemia
mitochondria function
bioenergetics
non-enzymatic glycosylation
diabetic markers
in vivo study
title The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons
title_full The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons
title_fullStr The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons
title_full_unstemmed The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons
title_short The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons
title_sort janus face of pamam dendrimers used to potentially cure nonenzymatic modifications of biomacromolecules in metabolic disorders a critical review of the pros and cons
topic PAMAM dendrimers
diabetes mellitus
hyperglycaemia
mitochondria function
bioenergetics
non-enzymatic glycosylation
diabetic markers
in vivo study
url http://www.mdpi.com/1420-3049/18/11/13769
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