Chlorinative stress in age-related diseases: a literature review

Abstract

Aging is an agglomerate of biological long-lasting processes that result being inevitable. Main actors in this scenario are both long-term inflammation and oxidative stress. It has been proved that oxidative stress induce alteration in proteins and this fact itself is critically important in the pathophysiological mechanisms leading to diseases typical of aging. Among reactive species, chlorine ones such as hypochlorous acid (HOCl) are cytotoxic oxidants produced by activated neutrophils during chronic inflammation processes. HOCl can also cause damages by reacting with biological molecules. HOCl is generated by myeloperoxidase (MPO) and augmented serum levels of MPO have been described in acute and chronic inflammatory conditions in cardiovascular patients and has been implicated in many inflammatory diseases such as atherosclerosis, neurodegenerative conditions, and some cancers. Due to these data, we decided to conduct an up-to-date review evaluating chlorinative stress effects on every age-related disease linked; potential anti-oxidant countermeasures were also assessed. Results obtained associated HOCl generation to the aging processes and confirmed its connection with diseases like neurodegenerative and cardiovascular pathologies, atherosclerosis and cancer; chlorination was mainly linked to diseases where molecular (protein) alteration constitute the major suspected cause: i.e. inflammation, tissue lesions, DNA damages, apoptosis and oxidative stress itself. According data collected, a healthy lifestyle together with some dietary suggestion and/or the administration of nutracetical antioxidant integrators could balance the effects of chlorinative stress and, in some cases, slow down or prevent the onset of age-releated diseases.

Origin and pathophysiology of protein carbonylation, nitration and chlorination in age-related brain diseases and aging

“…Thus, the toxicity of HOCl towards central nervous system tissue was shown [ 153 – 155 ]. Furthermore, MPO was reported to be expressed with increased levels in the cerebral tissue of patients affected by AD [ 156 ] and 3-chlorotyrosine as a biomarker of HOCl production was detected in proteins from AD hippocampus. The level of 3-chlorotyrosine in the samples from diseased brain was three-fold higher compared to control samples [ 150 ].…”

Diethyl Selenodiglycolate: An Eco-Friendly Synthetic Antioxidant with Potential Application to Inflammatory Disorders

“…37 However, excessive production of HOCl either in sterile conditions or in unsolved inflammation is associated with tissue damage and chronic inflammatory diseases, including arthritis, 38 cystic fibrosis 39 and neurodegenerative 40,41 and cardiovascular disease. 42 The constant rate reaction of diethyl selenodiglycolate with HOCl was measured comparing to a standardized sulfide (Fmoc-Met) demonstrating a very high kinetic constant. The oxidant-scavenger capacity of selenide was ) were incubated in the absence or presence of different concentrations of diethyl selenodiglycolate (0.5, 1.0, 10, 25 and 50 µM) in PBS/glucose at 37 °C and activated with PMA (100 ng mL −1 ).…”

The Cu(II) reductase RclA protectsEscherichia coliagainst the combination of hypochlorous acid and intracellular copper

“…Copper accumulates in host tissues during inflammation (72, 73), as do RCS (74, 75). Our discovery that even very low concentrations of extracellular copper can protect bacteria against RCS both in vitro and in vivo adds a new and important facet to understanding copper’s role in innate immunity.…”