Acne vulgaris is a common inflammatory skin condition of the pilosebaceous unit that affects most individuals between 12 and 25 years of age [1]. It manifests in two forms: classic acne, which usually appears at the age of 14, and late-onset acne, which occurs around the age of 30. Although females are more prone to acne, males are more likely to develop severe forms [2].

The major pathogenic factors that contribute to the onset and progression of acne lesions are the alteration of the keratinization process, increased sebum production, colonization with Cutibacterium acnes (C. acnes, formerly: Propionibacterium acnes), and inflammation. However, it is worth noting that genetic factors also play a significant role ^[3][4][5][3,4,5]. Altered keratinization can lead to the formation of comedones, while changes in sebum composition such as a reduction in the amount of linoleic acid can cause hyperkeratinization ^[6][7][6,7]. Hormones, especially androgens, are powerful inductors of sebaceous gland secretion and modulate keratinocyte proliferation ^[1][2][1,2]. Excessive sebum production creates a favorable environment for bacterial growth, which, in turn, leads to inflammation [7].

The skin microbiome is a community of microorganisms that reside on the skin and plays a crucial role in maintaining skin homeostasis. C. acnes is a Gram-positive anaerobic microorganism that is part of the normal flora and contributes to the pathogenesis of acne [8]. Changes in the skin microbiome, which in most cases involve a decrease in microbial diversity and an increase in pathogenic bacteria, play a significant role in the appearance of acne lesions [9]. Although initially believed that C. acnes hyperproliferation is essential in the pathogenesis of acne, in fact, the severity of acne is associated with the loss of diversity of C. acnes phylotypes. Phylotype IA1 is dominant in patients with acne. The loss of C. acnes phylotype diversity acts as a promoter of immune system activation at the skin level. When a skin explant is incubated with only phylotype IA1, there is an increase in the expression of inflammation markers such as interleukin 6 (IL-6), IL-8, IL-10, and IL-17. This is in contrast to incubation with a combination of phylotypes IA1 + II + III, which does not lead to such upregulation [10]. It seems that C. acnes in acne lesions is more virulent than the strains isolated from normal skin. Acne-related strains have the ability to release porphyrins that lead to the formation of reactive oxygen species (ROS) and trigger an inflammatory process in keratinocytes, which is associated with an oxidant–antioxidant imbalance [10].

ROS have deleterious effects on cell components (protein-derived enzymes, lipid-rich membranes, nucleic acids, and carbohydrates), causing functional and structural alterations. Depending on the molecular targets of ROS action, OS markers show a wide variety. Therefore, they can be divided into four main classes: markers of lipid peroxidation, DNA oxidative damage, protein oxidation, and carbohydrate oxidation. The antioxidant molecules also represent an important source of biomarkers to evaluate OS ^[11][12][11,12]. Table 1 summarizes the main markers of OS used in clinical practice.

The most used markers to assess lipid peroxidation are malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and isoprostanes. MDA is a stable aldehyde originating from the breakdown of polyunsaturated fatty acids during the lipid peroxidation process ^[17][18][17,18]. It is a highly reactive compound and by interacting with proteins may alter their structure, resulting in neoepitopes, responsible for the initiation of an inflammatory process. Its toxic activity was linked to mutagenic effects [19]. Another aldehyde, 4-HNE, acts as a secondary messenger for OS, regulating various signaling pathways and gene expression [19]. Isoprostanes are compounds structurally similar to prostaglandins, but are generated independently of cyclooxygenase through the peroxidation of arachidonic acid by a non-enzymatic pathway. F2 isoprostanes represent the most significant group of isoprostanes [20].

One of the primary effects of OS is the oxidative damage of DNA; nuclear DNA is particularly vulnerable to OS. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) is a crucial marker of DNA oxidation, and high levels have been detected in various types of tumors [21]. Another common marker of nucleic acid oxidation is 7,8-dihydro-8-oxoguanine (8oxoGuo), a product of RNA oxidation. 8oxoGuo promotes protein synthesis deregulation and the generation of structurally modified proteins [22].

Protein oxidation leads to thiol oxidation, aromatic hydroxylation, and carbonyl group formation [23]. Carbonyl groups are commonly used to detect protein oxidation, but cannot exactly indicate the source of OS [24]. Thiols are found in the structure of amino acids (e.g., cysteine) and proteins, and exert an antioxidant activity [25]. During periods of OS, thiols interact with prooxidant molecules, leading to their transformation into compounds that have reduced reactivity. Thiols enter the oxidation reaction and generate disulfides through the transfer of excess electrons from ROS to thiols. Disulfides participate in the augmentation of OS and weaken the antioxidant system [26]. Thiol–disulfide exchange reactions are crucial in cellular homeostasis. The transformation of thiols into disulfides is a reversible reaction ^[27][28][27,28]. To evaluate thiol disulfide homeostasis, specific markers are used including native thiol, total thiol, and disulfides [29]. In recent years, a new marker for protein oxidation, namely, ischemia-modified albumin (IMA), has been intensively studied. Albumin, the primary protein found in human plasma, is crucial for maintaining body homeostasis. Its deficiency has been linked to higher mortality rates and an increased risk of acute coronary heart disease. The albumin can bind certain metals such as cobalt, copper, and nickel to its amino terminal end. When the body undergoes ischemia or OS, the structure of the amino terminal end of albumin is altered. This altered version of albumin is known as IMA ^[30][31][30,31].

Advanced glycation end products (AGEs) are a diverse group of compounds generated by irreversible nonenzymatic reactions including carbohydrates, proteins, lipids, or nucleic acids [32]. Pentosidine, carboxymethyllysine, and methylglyoxal are the most widely known AGEs and are used as biomarkers [32]. Although they are produced continuously under physiological conditions, they do not accumulate due to receptor systems that bind and remove them. When high amounts of AGEs accumulate, they can cause various effects such as an alteration in vasoregulation, the accumulation of extracellular matrix, inflammation, and dysregulated expression of growth factors ^[33][34][33,34]. The receptor for advanced glycation end products (RAGE) is a transmembrane receptor expressed in small amounts in tissues, but its expression increases when its ligands accumulate. The interaction between AGEs and RAGE leads to the augmentation of OS and the development of an inflammatory process by interrupting normal intracellular signaling pathways [35].

Measuring the concentrations of oxidant species is difficult, time-consuming, and expensive, therefore, considering that the effects of oxidant molecules are additive, the determination of total oxidant status (TOS) is preferable [36]. Along the same line, due to the difficulty of measuring different antioxidant molecules individually and considering their cumulative antioxidant effects, the total antioxidant status (TAS) of a sample is measured. OSI levels are calculated using the following formula: OSI (arbitrary units) = TOS (µmol H2O2Eq/L)/TAS (µmol Trolox Eq/L) [37].