Redox imbalance in biological systems is associated with a complex interplay of oxidative pathways leading to more or less extensive degradation and breakdown of important cellular constituents including chiefly lipids, such as polyunsaturated fatty acids (PUFAs), as well as carbohydrates and proteins, among others. PUFA oxidation is a central event in lipid peroxidation and is associated with a chain reaction involving peroxide intermediates. These latter eventually break down to give α,β-unsaturated aldehydes, including 4-hydroxy-2-nonenal (HNE), acrolein, crotonaldehyde, and dialdehydes, such as malondialdehyde, glyoxal and methylglyoxal. Oxidative stressrelated aldehydes (OSRAs) are currently recognized to play a complex and crucial role in the onset and progression of several disease states, including vascular diseases, neurodegeneration and cancer. An important role of aldehydes in lipofuscinogenesis and age-related disorders has also been demonstrated. Besides being the measurable end product of lipid peroxidation and oxidative cell injury, aldehydes can act themselves as amplifiers of damaging events through covalent reaction with cellular targets such as proteins and nucleic acids. HNE, for example, has been implicated in a variety of cytopathological effects associated to oxidative stress and is currently one of the best recognized and most studied cytotoxic products of lipid peroxidation. The ability of glyoxal to cause interstrand DNA crosslinks is another remarkable example for the active role of aldehydes in mediating toxic mechanism in disease states, and the activation of the glyoxalase system to control glyoxal-mediated cell damage is indirect evidence of the impact of these processes on the progression of disease. Several conditions have been associated with an increase in the levels of endogenous aldehydes, including Fanconi anaemia, and the impact of this phenomenon may vary from one disease to the other depending on levels and potential targets involved, as well as the underlying specific pathways of toxicity. Starting from an initial survey of the basic mechanisms of aldehyde generation from lipid peroxidation and other oxidative processes following the onset of redox imbalance, this chapter aims at addressing a number of central issues in oxidative stress-related disorders: 1) what are the mechanisms of OSRAs toxicity in the progression and final outcome of the disease? 2) What are the main targets of OSRAs and what is the role of these interactions in the etiopathogenesis of oxidative stress-related disease states? 3) Can OSRA quantitation yield clues about the advancement and outcome of diseases? Far from being comprehensive, the present survey seeks rather to provide an inspiring and critical perspective of the biomedical relevance of aldehydes as markers of redox imbalance and their potential diagnostic and prognostic value with special reference to Fanconi anaemia and rare cancer-prone diseases

Aldehydes as markers of redox imbalance in fanconi anemia and in other oxidative stress-related disorders / Manini, Paola; D'Ischia, Marco. - (2015), pp. 69-92.

Aldehydes as markers of redox imbalance in fanconi anemia and in other oxidative stress-related disorders

MANINI, PAOLA;D'ISCHIA, MARCO
2015

Abstract

Redox imbalance in biological systems is associated with a complex interplay of oxidative pathways leading to more or less extensive degradation and breakdown of important cellular constituents including chiefly lipids, such as polyunsaturated fatty acids (PUFAs), as well as carbohydrates and proteins, among others. PUFA oxidation is a central event in lipid peroxidation and is associated with a chain reaction involving peroxide intermediates. These latter eventually break down to give α,β-unsaturated aldehydes, including 4-hydroxy-2-nonenal (HNE), acrolein, crotonaldehyde, and dialdehydes, such as malondialdehyde, glyoxal and methylglyoxal. Oxidative stressrelated aldehydes (OSRAs) are currently recognized to play a complex and crucial role in the onset and progression of several disease states, including vascular diseases, neurodegeneration and cancer. An important role of aldehydes in lipofuscinogenesis and age-related disorders has also been demonstrated. Besides being the measurable end product of lipid peroxidation and oxidative cell injury, aldehydes can act themselves as amplifiers of damaging events through covalent reaction with cellular targets such as proteins and nucleic acids. HNE, for example, has been implicated in a variety of cytopathological effects associated to oxidative stress and is currently one of the best recognized and most studied cytotoxic products of lipid peroxidation. The ability of glyoxal to cause interstrand DNA crosslinks is another remarkable example for the active role of aldehydes in mediating toxic mechanism in disease states, and the activation of the glyoxalase system to control glyoxal-mediated cell damage is indirect evidence of the impact of these processes on the progression of disease. Several conditions have been associated with an increase in the levels of endogenous aldehydes, including Fanconi anaemia, and the impact of this phenomenon may vary from one disease to the other depending on levels and potential targets involved, as well as the underlying specific pathways of toxicity. Starting from an initial survey of the basic mechanisms of aldehyde generation from lipid peroxidation and other oxidative processes following the onset of redox imbalance, this chapter aims at addressing a number of central issues in oxidative stress-related disorders: 1) what are the mechanisms of OSRAs toxicity in the progression and final outcome of the disease? 2) What are the main targets of OSRAs and what is the role of these interactions in the etiopathogenesis of oxidative stress-related disease states? 3) Can OSRA quantitation yield clues about the advancement and outcome of diseases? Far from being comprehensive, the present survey seeks rather to provide an inspiring and critical perspective of the biomedical relevance of aldehydes as markers of redox imbalance and their potential diagnostic and prognostic value with special reference to Fanconi anaemia and rare cancer-prone diseases
2015
1634822978
Aldehydes as markers of redox imbalance in fanconi anemia and in other oxidative stress-related disorders / Manini, Paola; D'Ischia, Marco. - (2015), pp. 69-92.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/639760
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