4-Hydroxynonenal – major bioactive marker of lipid peroxidation

  • Neven Zarkovic Rudjer Boskovic Institute
  • Kamelija Zarkovic University of Zagreb School of Medicine Clinical Hospital Centre Zagreb, Division of Pathology


While oxidative stress is generally considered mostly as pathogenic component of stress and age associated diseases, reactive aldehydes such as 4-hydroxy-2-nonenal (HNE) are considered mostly as the end-products of lipid peroxidation, which act as a “second toxic messenger of free radicals”. However, findings of growth regulating activities of HNE that overlapped with the development of the first monoclonal and polyclonal antibodies specific for the HNE-protein adducts led to the introduction of qualitative and quantitative determinations of the HNE presence in various (patho)physiological processes and to the change of consideration of the aldehyde’s bioactivities from toxicity into cell signaling, growth regulation and hormesis.

Thus, the progress in the fields of the redox signaling and broad bioactivities or reactive oxygen and nitrogen species changed our overall approach to oxidative stress and to consideration of HNE not only as toxic but more general as a “second messenger of free radicals” and the growth regulating factor. Moreover, findings of the HNE-protein adducts in various organs under physiological circumstances support the concept of “oxidative homeostasis”, which implies that oxidative stress and lipid peroxidation are not only pathological but also physiological processes. Accordingly, HNE could play important role in oxidative homeostasis, while complementary research approaches might reveal the relevance of the aldehydic-protein adducts as major bioactive markers of oxidative stress, lipid peroxidation and oxidative homeostasis.


4-Hydroxynonenal, lipid peroxidation, oxidative stress, pathophysiology, reactive aldehydes aling, growth regulation and hormesis.





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