Reactive Carbonyl Species as Potential Pro-Oxidant Factors Involved in Lichen Planus Pathogenesis

Abstract

The constant generation of reactive carbonyl species (RCSs) by lipid peroxidation during aerobic metabolism denotes their involvement in cell homeostasis. Skin represents the largest organ of the body that is exposed to lipid peroxidation. Previous studies have suggested the involvement of oxidative stress in the development of lichen planus (LP), a chronic inflammatory skin condition with a complex pathogenesis. The aim of our study is to investigate a panel of pro-oxidants (4-hydroxy-nonenal (4-HNE), thiobarbituric acid reactive substances (TBARS), and malondialdehyde (MDA)), the total antioxidant status (TAS), and thiol-disulfide homeostasis parameters (TDHP), including total thiol (TT), native thiol (NT), disulfides (DS), DS/NT ratio, DS/TT ratio, and NT/TT ratio. The comparative determinations of serum levels of 4-HNE, TBARS, and MDA in patients with LP (n = 31) and controls (n = 26) show significant differences between the two groups (4-HNE: 7.81 ± 1.96 µg/mL vs. 6.15 ± 1.17 µg/mL, p < 0.05, TBARS: 4.23 ± 0.59 µmol/L vs. 1.99 ± 0.23 µmol/L, p < 0.05, MDA: 32.3 ± 6.26 ng/mL vs. 21.26 ± 2.36 ng/mL). The serum levels of TAS are lower in LP patients compared to the control group (269.83 ± 42.63 µmol/L vs. 316.46 ± 28.76 µmol/L, p < 0.05). The serum levels of TDHP are altered in LP patients compared to controls (NT: 388.10 ± 11.32 µmol/L vs. 406.85 ± 9.32., TT: 430.23 ± 9.93 µmol/L vs. 445.88 ± 9.01 µmol/L, DS: 21.06 ± 1.76 µmol/L vs. 19.52 ± 0.77µmol/L). Furthermore, a negative association between pro-oxidants and TAS is identified (4-HNE – rho = −0.83, p < 0.01, TBARS – rho = −0.63, p < 0.01, and MDA – rho = −0.69, p < 0.01). Understanding the mechanisms by which bioactive aldehydes exert their biological effects on the skin could help define effective therapeutical strategies to counteract the cytotoxic effects of these reactive metabolic intermediates.

Oxidative Stress in Cutaneous Lichen Planus—A Narrative Review

“…MDA and 4-HNE are among the most important reactive carbonyl species resulting from lipid peroxidation [ 53 ]. Lipid peroxidation products such as MDA and 4-HNE can alter cellular homeostasis.…”

“…Two studies evaluated protein oxidation in patients with CLP and used markers thiol disulfide homeostasis parameters (native thiol, total thiol, and disulfide) [ 52 , 53 ]. Kalkan et al analyzed thiol disulfide homeostasis in 81 patients with CLP.…”

“…However, in a previous study, we found significantly lower levels of NT and TT and increased levels of DS in patients with CLP compared to the control group. These results may be the consequence of increased levels of pro-oxidants that exhausted the antioxidant systems [ 53 ].…”

“…The increased consumption of thiols and a high pro-oxidant potential of the serum lead to cell damage and could be a key step in the onset and progression of LP lesions. Under oxidative stress conditions, many processes, including cell proliferation, apoptosis, detoxification, and antioxidant defense, are altered [ 53 ].…”

Risk of metabolic syndrome in patients with lichen planus: A systematic review and meta-analysis

“…Some researchers are of the view that chronic inflammatory markers are useful predictors of cardiovascular events [31]. Notably, oxidative stress injury is implicated as an important pathogenetic contributor to MS. Mitran et al reported increased lipid peroxidation and impairment of the antioxidant defense mechanism in patients with LP [32].…”