## 3 Oxidative Stress Biomarkers Involved in Psoriasis Inflammation
### Paraaxonase (PON)  
Paraaxonase (PON), a serum enzyme bound to high-density lipoprotein (HDL), plays a crucial role in hydrolyzing organic phosphates and lipid peroxides, thereby protecting against LDL oxidation and potentially reducing disease risks [27; 28]. The paraoxonase family comprises PON1, PON2, and PON3, all of which are connected with mitochondria-associated membranes (MAMs) [29]. MAMs have a crucial function in multiple cellular processes, such as regulating mitochondrial metabolism by safeguarding mitochondrial membranes against oxidative stress. This ensures the correct functioning of mitochondria and helps to decrease the formation of mtROS [29]. Among the variants of PON, psoriasis patients were found to have lower PON1 activity in their blood compared to healthy individuals, indicating that psoriasis is linked to oxidative stress and a weakened antioxidant system. This may contribute to the development and advancement of psoriasis and its associated complications [30]. PON1 is a glycoprotein with a molecular weight of 43-45 kDa and it is situated on the q21-q22 region of the long arm of chromosome 7 in humans [31]. The two primary variations of PON1 are L55M and Q192R, in which Leucine (L) at position 55 is substituted with Methionine (M), and Glutamine (Q) at position 192 is replaced with Arginine (R), respectively [30]. The paraoxonase activities of the 55 M and 192 R isozymes have been documented to exhibit lower levels compared to the 55 L and 192 Q enzymes [32]. There is an inverse relationship between serum PON1 activity and serum HDL susceptibility to oxidation in individuals [30]. The PON1 gene displays genetic variations that impact the activity, stability, and selectivity of the enzyme. A study investigates the association between PON1 polymorphisms (rs662 and rs854560) and psoriasis susceptibility in a western Mexico population involving 104 psoriasis patients and 124 controls [27]. The results demonstrate elevated lipid profile levels in patients, accompanied by reduced paraoxonase and arylesterase activity. According to the study conducted by [PERSON] et al. (2020), the G allele of rs662 is correlated with a higher chance of developing psoriasis, whereas the T allele of rs854560 is connected with a reduced susceptibility to the condition. In addition, a research study examines the correlation between the PON1 55 M allele and psoriasis in a case-control study involving 100 individuals with psoriasis and 100 healthy individuals [33]. The presence of the PON1 55 M allele was determined to be associated with psoriasis using polymerase chain reaction-restriction fragment length polymorphism. Patients with the PON1 M allele showed increased levels of MDA, as well as decreased arylesterase (ARE) activity. This indicates a connection between oxidative stress, impaired antioxidant defense, and the development of psoriasis [33]. Reduced PON1 activity in individuals with psoriasis implies its role in disease pathology, contributing to oxidative stress and inflammation by disrupting the balance between ROS production and antioxidant defenses. Studies have demonstrated correlations between PON levels, disease severity, and chronic inflammation markers in psoriasis patients. In correlation with psoriasis severity, [PERSON] et al. observed diminished activity of PON1 and arylesterase and they also noted a negative relationship between lipoprotein levels and PON1 activity, indicating that individuals with higher lipoprotein levels may experience increased susceptibility to oxidative damage [34]. Similarly, lower PON1 activity correlated with higher lipoprotein levels, exacerbating oxidative stress susceptibility in psoriasis patients [35]. This decrease, which was positively correlated with the severity of the condition, might be the consequence of ROS-induced antioxidant inactivation [35]. Furthermore, its robust antioxidant capabilities enable it to neutralize ROS and hydrolyze lipid peroxides, thereby mitigating oxidative stress.