## 4 Discussion
The inhalation of PM\({}_{2.5}\) triggers an oxidative stress-induced inflammatory response characterized by increased lipid peroxidation and a depletion of the antioxidant defense system, leading to decreased GSH, CAT, and SOD activity [1, 2, 3, 13, 16, 72,73]. As a consequence of the inflammatory response, there is an upsurge in the secretion of cytokines, such as TNF-\(\alpha\), IL-6, CXCL1, and CXCL2 [1, 2, 3, 16, 72, 73]. Indeed, lipid peroxidation is an autocatalytic process that results in the oxidative degradation of cell membranes [74,75]. Destruction of the cell membrane by lipid peroxidation promotes the formation of toxic reactive aldehyde metabolites and cell death represented by MDA, i.e., free radicals [76,77]. Oxidative damage can affect a range of biological macromolecules, including but not limited to proteins, DNA, and lipids, as a result of exposure to various forms of ROS [77,78]. During the lipid peroxidation process, the amount of MDA produced is used to determine the lipid peroxidation index [77]. As an endogenous antioxidant, it serves as a representative molecule that effectively eliminates ROS even at low concentrations within cells, thereby controlling tissue damage [79]. SOD is also an endogenous antioxidant enzyme that acts as part of a cell's enzymatic defense system, and CAT is a representative endogenous antioxidant enzyme that converts toxic hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)) to harmless water (H\({}_{2}\)O) [80]. The decrease in GSH, SOD and CAT activity indicates the failure of compensatory action due to oxidative stress induced by inhalation of PM\({}_{2.5}\)[1, 2, 3, 13, 16]. PM\({}_{2.5}\) causes an increase in the level of chemotactic cytokines CXCL1 and CXCL2 in blood and respiratory tissues as part of an inflammatory response [16,72,73]. NF-kB is recognized as having an important role in inflammation associated with some adhesion molecules, ROS, and binds to promoters encoded in IL-6, IL-1, and TNF-\(\alpha\) to trigger their transcription [81,82]. It also regulates various cytokine expressions, including IL-6, IL-10, CXCL1, and CXCL2, which are directly related to the inflammatory responses [83]. The amount of TNF-\(\alpha\), IL-6, CXCL1, and CXCL2 increases with an increase in NF-kB expression even during PM\({}_{2.5}\)-induced lung injury [16,72]. Furthermore, p38 MAPK, PI3K, and Akt signaling pathways are involved in ROS-induced oxidative stress caused by PM\({}_{2.5}\)-induced lung injury [42,84]. In particular, Akt activity triggers an inflammatory response by increasing the secretion of inflammatory chemotactic factor CXCL1 through an increase in NF-kB expression [85]. PTEN is a representative tumor suppressor gene, and abnormalities in PTEN cause the pathogenesis of several malignant tumors [86, 87, 88]. The MAPK signaling pathway regulates the expression of PTEN [89]. In other words, the inhibition of the MAPK signaling pathway maintains PTEN expression and significantly reduces the occurrence of malignant tumors [88,90]. The possibility of malignant tumor formation increases in PM\({}_{2.5}\).treated lung tissues, as there is a significant decrease in the expression of the tumor suppressor gene PTEN [91; 92]. In the current study, the intranasal injection of PM\({}_{2.5}\) (1 mg/kg) showed significant lipid peroxidation in lung tissue, increased MDA and ROS levels, decreased GSH, CAT, and SOD activity, increased inflammatory cytokines TNF-\(\alpha\), IL-6, CXCL-1, and -2, together with inflammation-related NF-\(\kappa\)B and oxidative stress, increased PI3K, Akt, and p38 MAPK expression, and decreased PTEN expression. Meanwhile, oxidative stress and inflammatory lung damage through PM\({}_{2.5}\)-induced NF-\(\kappa\)B, p38 MAPK, and PI3K/Akt expression decreased in a dose-dependent manner in all three IAP-extract-administered groups. The IAP400 group showed anti-inflammatory and antioxidant activity comparable to that in the DEXA group, suppressing PM\({}_{2.5}\)-induced sub-acute lung injury.