It is widely accepted that life in the human organism must be in balance and that too much of anything is harmful. Aerobic cells that cannot survive without oxygen can also be damaged by too much oxygen. Joseph Priestley was the first to realize that oxygen has the potential to harm humans. This happens due to the excessive production of ROS[21], which is an essential part of the normal functioning of our body. Under normal conditions, oxidants and antioxidants are in balance.
OS arises as a result of the increase in the production speed of ROS, i.e., oxidants or the insufficiency of the antioxidant defense mechanism that can compensate for this increase. Exogenous stimuli, such as ultraviolet radiation, trauma, and stress, and endogenous stimuli, including cellular metabolism, proliferation, differentiation, apoptosis, and immune reactions cause the accumulation of ROS[22]. ROS have been associated with antimicrobial defense, inflammation, cancer, radiation damage, photobiological damage, and aging. As a result, DNA base damage, protein oxidation, and lipid peroxidation occur, and the balance of the cell is disrupted and destroyed[7, 21, 22]. Recently, it has been reported that internal electromagnetic field distributions spread during the formation reactions of ROS and may lead to cellular genetic changes and consequently DNA damage[23]. There are many enzymatic (superoxide dismutase, catalase, glutathione peroxidase) or non-enzymatic (such as glutathione, vitamin C, E, beta-carotene) pathways of antioxidant defense[24].
Previous research reported the role of OS in the etiopathogenesis of some skin diseases, such as vitiligo, psoriasis and Behçet's disease[7–9]. Studies supporting the role of OS in the pathogenesis of AA are also increasing[7–11]. While there are pioneering studies on this subject investigating lipid peroxidation products and antioxidant enzyme levels[5, 7, 10], recent studies have also focused on TAS, TOS and OSI levels[6, 10, 11].
In patients with AA, antioxidant enzyme levels were found to be lower based on plasma and erythrocyte samples by Naziroğlu and Kokcam[25], blood and scalp tissue samples by Abdel Fattah et al.[26] and serum samples by Koca et al[27]. Additionally, aforementioned studies showed an elevation in lipid peroxidation. In contrast, two studies examining scalp tissues in patients with AA reported higher antioxidant levels[28, 29].
The literature also contains studies examining TAS, TOS and OSI levels in AA[6, 10, 11]. Bakry et al. [6] evaluated serum malondialdehyde (MDA), TAS, TOS and OSI in three patient groups, namely patch-type AA, alopecia totalis, and alopecia universalis. They found an increase in the MDA, TOS and OSI values and a decrease in the TAS value and concluded that these parameters were related to disease severity. Bilgili et al. [10] also reported an increase in the TOS and OSI values and a decrease in the TAS value. In a detailed study of 60 patients with AA and 50 controls, Dizen-Namdar et al. [11] reported that the TOS and OSI values were higher in the AA group, but there was no significant difference between the two groups in terms of TAS. In our study, OS was evaluated to be higher in the AA group based on higher TOS and OSI values and the lower TAS value. This supports the results of Bakry et al. [6] and Bilgili et al[10]. In contrast, in a study by Motor et al.[15], no significant different was found in any of the three values between the patient and control groups.
Increasing ROS activate the intracellular antioxidant defense mechanism. Thus, the activation of superoxide dismutase (SOD) and glutathione peroxidase enzymes increases[26, 28]. It is considered that the increase in these antioxidant enzyme values increases in response to OS, and this indicates that the antioxidant defense system works adequately[29]. However, excessively increased oxidative radicals in the cell may reduce the antioxidant protective mechanism and cause an increase in OS[30, 31]. In our study, although disease severity was mild and the duration of the disease was short, antioxidant protection was significantly decreased, and TOS was significantly increased. Increased TOS and decreased TAS reflect a high oxidative stress state in cells and indicate inflammation and cell destruction.
It has been reported that exposure to OS disrupts the structure and function of the SOD enzyme, which can cause antigenic stimulation and initiate autoimmunity[16]. Mitochondrial membrane damage caused by OS also results in apoptosis by secreting enzymes and is effective in the emergence of autoimmunity[32, 33]. Low TAS values in AA cases in our study indicate a high oxidant status that exceeds antioxidant defense or defective antioxidant activity. In light of other studies, this suggests that OS may have a primary role in the etiopathology of AA[10, 11, 15].
Ischemia can lead to ROS production through the proinflammatory chain. It has been reported that while IMA increases in polycystic ovarian syndrome, diabetic nephropathy, multiple sclerosis, and some cancers, it does not increase in immune system disorders, gastrointestinal diseases, and non-ischemic heart diseases[18, 34–37].
Few studies have also reported high serum IMA levels in some dermatological diseases associated with OS, such as psoriasis[8], vitiligo[38], Behçet's disease[39], AA[12], and telogen effluvium[40]. In another study, it was reported that increased IMA levels in patients with AA might be associated with the antioxidant/oxidant imbalance and cardiovascular disease risk[19]. In our patient group, the serum IMA level was associated with an insignificant increase compared to the healthy population. In a recent meta-analysis[41], a total of 18 studies investigating the relationship between OS and AA were examined and the results indicated that patients with AA had impaired oxidative balance, pointing to increased levels of serum MDA, nitric oxide, and TOS, as well as decreased levels of serum SOD, paraoxonase, glutathione peroxidase, and TAS[38]. Our study supports this meta-analysis and provides additional information on IMA values in mild AA cases.
In meta-analysis by Prakash Acharya et al, the serum TAC was lower and serum TOC was higher in the AA group compared to the study group, whereas there were no significant differences in the level of serum OSİ between AA group and healthy control group. In addition, oxidative damage products were also found to be higher in the AA group in comparison to the control group[41].
In a recent study evaluating the serum proinflammatory cytokine levels, which could be considered as a signature of oxidative stress, serum levels of interferon γ (IFN-γ), interleukin- (IL-) 1β, and IL-6 were found higher(p < 0,05) in the AA group compared to the control group[42].
The main limitation of our study was the small number of patients with AA. However, our patient group included only new-onset focal AA cases and did not include other forms of the disease, such as alopecia totalis and alopecia universalis. This homogeneity was an advantage because the results were obtained from a focal group and may not be considered as a limitation. Secondly, we were not able to investigate the endogenous or exogenous factors that increased OS in our patients. Therefore, the causal relationship between OS and the levels of antioxidative vitamins and trace elements that can be given as treatment could not be clearly determined. Lastly, we evaluated the patients only at baseline and not after treatment with antioxidants.