Free radical studies of components of the extracellular matrix: contributions to protection of biomolecules and biomaterials from sterilising doses of ionising radiation

Abstract

The purpose of the current review is show how the principles and techniques of radiation chemistry have enabled the direct reactions of free radicals with biomolecules and biomaterials to be investigated at the molecular level. In particular, the review focusses on the free radical-induced fragmentation of glycosaminoglycans. Glycosaminoglycans are large linear polysaccharides consisting of repeating disaccharide units and are important components of the extracellular matrix (ECM) either in free form (hyaluronan) or as a component of proteoglycans. Oxidative damage of the extracellular matrix components by either enzymatic or non-enzymatic pathways may have implications for the initiation and progression of a range of human diseases. These include arthritis, kidney disease, cardiovascular disease, lung disease, periodontal disease and chronic inflammation. Oxidative damage to hyaluronan by reactive oxidative species and thus the potential mechanism of damage to the ECM and its role in human pathologies is reviewed with particular focus on damage initiated by potential in vivo free radicals such as superoxide, carbonate and hydroxyl radicals. Such knowledge has also allowed radiation protecting systems to be developed so that sterilising doses of radiation can be delivered to sensitive biomolecules such as proteins and glycosaminoglycans, and also to sensitive biomaterials such as tissue allografts.

A critical review of recent knowledge of alcohol's effects on the immunological response in different tissues

“…Hyaluronic acid (HA) is an extracellular matrix glycosaminoglycan of variable molecular weight that can function as a pro‐ or anti‐inflammatory signaling molecule. For example, HA synthesis and fragmentation are increased in chronic respiratory diseases and in the bronchoalveolar lavage fluid of ARDS patients (Hallgren et al, 1989), potentially through amplified hyaluronidase activity and oxidant generation during inflammation (Parsons, 2018; Rees et al, 2008). In vitro and in vivo models of EtOH exposure include a murine alveolar macrophage cell line, MH‐S cells, treated with 0.08% EtOH for 3 days or a 12‐week EtOH feeding model (20% w/v in drinking water) in C57BL/6J mice (Morris et al, 2021).…”