4-Hydroxy-2-nonenal, a lipid peroxidation product, as a biomarker in diabetes and its complications: challenges and opportunities

Abstract

Over 30 million Americans are diagnosed with diabetes and this number is only expected to increase. There are various causes that induce complications with diabetes, including oxidative stress. In oxidative stress, lipid peroxidation-derived reactive carbonyl species such as 4-hydroxy-2-nonenal (4-HNE) is shown to cause damage in organs that leads to diabetic complications. We provided evidence to show that 4-HNE or/and 4-HNE-protein adducts are elevated in various organ systems of diabetic patients and animal models. We then discussed the advantages and disadvantages of different methodologies used for the detection of 4-HNE in diabetic tissues. We also discussed how novel approaches such as electrochemistry and nanotechnology can be used for monitoring 4-HNE levels in biological systems in real-time. Thus, this review enlightens the involvement of 4-HNE in the pathogenesis of diabetes and its complications and efficient methods to identify it. Furthermore, the article presents that 4-HNE can be developed as a biomarker for end-organ damage in diabetes such as diabetic cardiac complications.

Keywords:

• Diabetes
• diabetic cardiac complications
• reactive carbonyl species
• 4-hydroxy-2-nonenal (4-HNE)
• electrochemistry

Author contributions

All authors have made substantial contributions to the manuscript. SSP provided the conception and design for the manuscript and edited the manuscript. DD and AG performed the literature search, data analysis, and drafted the manuscript. BR drafted the figures, edited and submitted the manuscript. AR drafted a figure and edited the manuscript. XZ, GP and RAT provided their critical inputs while reviewing the manuscript. All authors approved the final version of manuscript for submission.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

SSP is supported by a grant from the National Heart, Lung, and Blood Institute [grant no. 1R01HL139877-01A1] and an internal grant from Henry Ford Health System [grant no. A10249].