Lipid Peroxidation End-Products as Modulators of Catabolic and Inflammatory Responses in Arthritis: A Review

Lipid peroxidation (LPO) is a free radical-related process occurring in biologic systems under enzymatic or nonenzymatic control, e.g. for the generation of lipid-derived aldehydes. There is increasing evidence that these aldehydes are causally involved in the pathogenesis of numerous diseases including diabetes, heart failure, atherosclerosis, and neurodegenerative process. 4-hydroxynonenal (HNE) is the most important aldehyde involved in oxidant injury. Classically, HNE was described for a long time as a marker of extensive oxidative stress in various tissues. Recent studies, however, showed that HNE can modulate cellular metabolism, inflammatory responses, as well as apoptosis via its effects on signaling/transcription regulation and protein modification. Interestingly, these pathological processes are all implicated to various degrees in arthritis, but no study has specifically reported the potential role of these aldehydes in rheumatic diseases. Therefore, this review focuses on the relevance of oxidative stress-induced HNE production to the pathophysiology of arthritis at inflammatory and catabolic levels.