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ORIGINAL ARTICLE
Year : 2022 | Volume
: 42
| Issue : 1 | Page : 11-15
Oxidant and antioxidant status in patients with female pattern hair loss with varying severity
Fathia M Khattab1, Amira S Al-Karamany2
1 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt
Correspondence Address:
MD Fathia M Khattab
Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, 44519
Egypt
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/ejdv.ejdv_38_19
Background Female pattern hair loss (FPHL), also known as female androgenic alopecia, is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including FPHL.
Aim This study was aimed to investigate the levels of oxidative stress biomarkers in patients with FPHL with varying severities.
Patients and methods The study involved 56 patients with FPHL and 46 healthy controls. Diagnosis was based on clinical examination and trichoscopic evaluation. Patients were grouped into three subgroups as follows: mild, moderate, and extensive. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase, total antioxidant capacity, and malondialdehyde (MDA).
Results Plasma levels of MDA in FPHL were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes superoxide dismutase and CAT were lower. Moreover, total antioxidant capacity was also low in patients with FPHL as compared with that of the controls. Higher MDA levels in the extensive FPHL subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the extensive FPHL subgroup, a significant negative correlation was observed between MDA and CAT levels.
Conclusion The data suggest that oxidative stress plays a key role in FPHL progress, which accelerates hair loss by causing microinflammation and fibrosis. The recognition of the effect of androgens and associated factors on the hair follicle cycle is essential for the development of new and effective treatment methods and may be employed as a biomarker index to assess the disease’s activity and to monitor its treatment.
Keywords: antioxidative, female pattern hair loss, oxidative
Female pattern hair loss (FPHL) is known as female androgenic alopecia. Androgens, growth factors, age, genetic susceptibility, racial factors, and local factors are incriminated in the pathogenesis of FPHL [1], and follicular miniaturization plays the leading role [2]. In the treatment of FPHL, limited success has been obtained with hair growth supporters and androgen metabolism modulators, which suggest that other pathogenic pathways may be considered [3].
Lipid peroxidation, glutathione derivatives, and nitric oxide are indicators of cellular destruction by reactive oxygen species (ROS) through oxidation [4]. All these markers have been identified to be significantly raised in patients with hair loss, providing evidence of the role of ROS in the mechanism of hair loss [5]. Lymphocytes-generated ROSs are also known to be closely correlated with the pathogenesis of a variety of inflammatory skin diseases [6],[7].
Antioxidant defense systems, such as the enzymes superoxide dismutase (SOD) and catalase (CAT), keep ROS production in check, thereby maintaining an appropriate cellular redox balance. Alterations in this redox balance resulting from elevated ROS levels and/or decreased antioxidant levels can lead to oxidative stress [8]. Lipid peroxidation, a process of oxidative degeneration of polyunsaturated fatty acids that are set into motion by ROS, leads to the formation of highly reactive aldehydes, such as malondialdehyde (MDA), and may be one of the reasons for cellular membrane damage [9].
In this study, we measured the levels of oxidative biomarkers in the plasma of patients with FPHL in Egyptian patients and compared them with respective levels in healthy controls. Furthermore, the study assessed the correlations between the levels of plasma oxidative biomarkers and disease severity.
Patients and methodsPatients
A total of 56 female patients with FPHL between the ages of 18 and 50 years were recruited from Outpatient Dermatology Zagazig University. Signed and informed consent was obtained from all the patients before the initiation of the study. The study was approved by the Ethical Review Committee.
Diagnosis was based on clinical examination and trichoscopic evaluation. Patients with varying disease severities (mild, moderate, and extensive) were included in the study. The Ludwig classification uses three stages to describe female pattern genetic hair loss: type I (mild), type II (moderate), and type III (extensive). Stage I begins with thinning on top of the head. In stage II, the scalp starts to show. All of the hair at the crown of the head may be lost when the hair loss progresses to stage III [10].
Based on this system, patients were graded into three groups as follows: mild, moderate, and extensive FPHL. Of the 56 patients evaluated, 17 patients were graded as mild, 20 were graded as moderate, and 19 patients were graded as extensive. Moreover, 47 healthy, unrelated female participants with mean age of 20.0±3.3 years from the same local region were selected as controls. Neither the patients nor the controls had received any topical and/or systemic drug therapy for at least 3 months before blood collection; none of them had any other coexistent disease.
Overall, 5 ml of peripheral blood was collected in EDTA tubes after 10–12 h of fasting. Plasma was separated by centrifugation at 2000 rpm for 5 min and stored at −80°C in aliquots for further use.
Determination of CAT and SOD activities in plasma
The activity of CAT in plasma was determined by adding 0.1 ml of plasma to an equal amount of 30% H2O2 and incubated for 3 min. Then, 3,5-dichloro-2-hydroxybenzene sulfonic acid and 4-aminophenazone were added, and the produced color was measured at 520 nm [11].
The plasma activity of SOD was measured according to the method described by Nishikimi et al. [12]. This assay relies on the ability of the enzyme to inhibit the phenazine methosulfate-mediated reduction of the nitroblue tetrazolium dye, and the produced color is measured at 560 nm.
Determination of plasma total antioxidant capacity
The level of plasma total antioxidant capacity (TAC) was measured by incubating 0.02 ml of plasma with 0.5 ml of reaction substrate for 10 min at 37°C. Then, the chromogen solution was added and incubated for a further 5 min. The change in color was measured at 505 nm [13].
Determination of plasma level of MDA
The lipid peroxidation end product, MDA, was measured in plasma according to the procedure described by Ohkawa et al. [14] The reaction mixture contained 0.1 ml of plasma, 0.2 ml of 8.1% SDS, 1.5 ml of 20% acetic acid, and 1.5 ml of 0.8% aqueous solution of thiobarbituric acid. A mixture of n-butanol and pyridine (15 : 1, v/v) was added, and the solution was mixed vigorously. After centrifugation at 4000 rpm for 10 min, the absorbance of the organic layer was measured at 532 nm.
Statistical analysis
It was performed using the IBM SPSS ver. 22.0 (IBM Co., Armonk, New York, USA). Quantitative data were expressed as mean±SD.
The following tests were used: Fisher exact test, Mann–Whitney test, Spearman’s correlation coefficient (r), and Wilcoxon signed ranks test. P values of less than 0.5 were considered to be significant.
ResultsThe results for the levels of oxidative stress biomarkers measured in the plasma of the FPHL patients are shown in [Table 1]. The mean activities of CAT and SOD, as well as the levels of TAC, were significantly lower in the plasma of patients as compared with that of those in the control group (P<0.0001). In contrast, the mean level of lipid peroxidation measured as MDA was significantly higher in the patients as compared with that of those in the control group (P<0.0001).
Table 1 Levels of oxidative biomarkers in patients with FBHL and controls[Table 2] illustrates the plasma levels of oxidative markers for the mild, moderate, and extensive FPHL subgroups. Results indicated that there were no significant differences in CAT levels in patients with FPHL of varying severity (P>0.05). However, the SOD levels were significantly lower in the extensive FPHL subgroup as compared with that of those in the mild and moderate subgroups (P<0.05). Similarly, the levels of SOD and TAC were significantly lower in the plasma of patients with extensive FPHL as compared with the levels in the mild and moderate FPHL (P<0.05). In contrast, the levels of the lipid peroxidative product MDA were significantly higher in the extensive FPHL subgroup as compared with the levels of those in the mild and moderate subgroups (P<0.05).
Table 2 Levels of oxidative biomarkers in patients with varying severities of FBHLThe correlations between the levels of plasma oxidative markers in patients with FPHL of differing severities are shown in [Table 3]. A positive correlation was observed between the activities of SOD and CAT in the plasma of FPHL. Furthermore, a positive correlation between the levels of TAC and CAT activity in the plasma of patients was noted. Interestingly, the levels of lipid peroxidation were found to be negatively correlated with the activities of CAT or SOD as well as with the TAC level in the plasma of FPHL. Therefore, further correlation studies were performed to investigate the effects of FPHL severity on the levels of oxidative and antioxidative biomarkers. A significant correlation between CAT activity and MDA levels in the plasma of patients with extensive FPHL was observed. However, no significant correlation was found in the mild and moderate FPHL subgroups.
Table 3 Correlation analysis of oxidative markers in the plasma of patients with FBHL Discussion FPHL frequently occurs in the second decade of life. The pathogenesis of this disease is multifactorial. Compelling evidence suggests that oxidative stress is involved in the onset of FPHL [15]. Oxidative stress results from disequilibrium between systemic signs of ROS and detoxifying and repairing the capacity of biological systems. Free radical production increases, whereas endogenous defense mechanisms decrease with aging. A key role of oxidative stress is also considered in hair graying and hair loss. Hair loss may be owing to nonandrogen signals in addition to androgens at an advanced age [16].
Human cells have both enzymatic and nonenzymatic antioxidant defense systems. The SOD-CAT system is a major enzymatic system that acts as the first line of defense against oxygen-derived free radicals; it controls ROS production by catalyzing the dismutation of the superoxide into hydrogen peroxide, which is further converted into water by CAT and is thus crucial in maintaining an appropriate cellular redox balance [17]. Alterations in this normal balance, which may occur owing to elevated ROS production and/or decreased antioxidant levels, can lead to a state of oxidative stress [18].
The results of this study demonstrated a significant elevation of plasma lipid peroxide levels in FPHL as compared with levels in healthy controls. In contrast, the activities of plasma SOD and CAT, as well as the level of TAC, were found to be significantly diminished in FPHLs as compared with those in healthy individuals. Previous studies have revealed that the level of lipid peroxidation increases in inflammatory diseases; moreover, its final product, MDA, is considered an indicator of the oxidative stress in the cells [19]. Then, the high plasma levels of MDA in our patients may be a result of cellular damage caused by ROS. The results suggest that FPHL is mediated, at least in part, by the increased generation of ROS, which may be attributed to reduced levels of antioxidant enzymes, including SOD or CAT [20]. In various diseases, it has been observed that the SOD-CAT system may be affected in a way of increasing and decreasing or in two different directions [21].
Similar to the present findings, Prie et al. [22] reported that serum levels of MDA in patients with androgenic alopecia were significantly higher than those of the controls. Moreover, they revealed significantly lower SOD activity in the patient group than in the control group.
Moreover, Cwynar et al. [23] reported that lipid peroxide levels were significantly increased in female patients with androgenic alopecia. However, in contrast, Amirnia et al. [24] found no statistical differences in MDA levels between patients with androgenic alopecia and normal individuals. Those two different results may be explained by the fact that the antioxidant system undergoes various interactions with environmental or genetic factors that affect its increase, decrease, or normal levels.
Moreover, the results revealed the association between the higher levels of oxidative stress biomarkers and the severity of FPHL among patients. The MDA levels were significantly elevated in the plasma of patients with extensive FPHL as compared with those in patients with mild and moderate FPHL. Moreover, SOD activity and TAC levels were significantly decreased in the plasma of patients with extensive FPHL as compared with the levels of patients with mild or moderate FPHL. No statistically significant difference was observed in CAT activity levels among patients with differing disease severity.
In contrast to the present results, Yenin et al. [25] did not identify a correlation between alopecia areata severity and the levels of antioxidant enzymes or MDA in the leukocytes. We assumed that this disagreement was most likely attributed to the difference in the source of samples used for measuring oxidative biomarker levels. In plasma, the levels of these markers do not indicate the origin of their production.
Data also revealed a significant negative correlation between CAT and MDA levels in patients with extensive FPHL, whereas no such significant correlation was noted for patients with mild or moderate FPHL. Moreover, no significant correlation was observed between SOD activity, TAC activity, and MDA levels in FPHL, irrespective of disease severity. These findings show that oxidative stress is involved in FPHL and may play an important role in its pathogenesis and development. Toxic molecules and ROS play a crucial part in the pathogenesis and severity of FPHL.In FPHL, the microinflammatory component is localized to the vicinity of the bulge stem cell niche. The inflammatory processes, the release of ROS, and inflammatory mediators alter the follicle immune milieu, and although not immediately destructive to the follicle, can over time dysregulate normal cycling dynamics and stem cell renewal [26].
ROS are also released from the lymphocytes in the inflamed tissues. The augmentation of ROS resulted in the exhaustion of the antioxidant enzymes, leading to the reduction of their plasma level. The alterations in oxidant/antioxidant status noted in this study may be utilized as a biomarker index for differentiating between varying levels of severity of FPHL and for evaluating the response to treatment.
This suggestion needs to be confirmed by conducting further studies on a larger number of patients with FPHL. The alterations in the antioxidant enzyme activities in the plasma of patients with FPHL might reflect a peripheral response of the hair follicle to increased oxidative stress. However, when antioxidants levels are measured in plasma, it is not possible to determine the origin of these enzymes.
ConclusionThis study showed that oxidative stress increases and antioxidant defense decreases in patients with FPHL. It appears likely that these changes are not the cause but rather the consequence of cutaneous inflammations. Thus, antioxidant oral supplementation or topical application may be an effective approach in improving the efficacy or avoiding the potentially damaging effects of the therapeutical agents. Further research is required for optimal planning of FPHL therapy, and it may be useful to include at least one antioxidant drug along with the currently used treatment combinations.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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