(1) Background: Ozone exposure is a promising tool for treating liver damage since it is known to control the release of free radicals and increase the expression of antioxidant enzymes. The objective is to investigate the main intracellular pathways activated after exposure to ozone, considering the dosage of antioxidant enzymes and markers of oxidative stress. (2) Methods: This systematic review was performed based on the PRISMA guidelines and using a structured search in MEDLINE (PubMed), Scopus, and Web of Science. Bias analysis and methodological quality assessments were examined using the SYRCLE Risk of Bias tool. (3) Results: Nineteen studies were selected. The results showed that the exposure to ozone has a protective effect on liver tissue, promoting a decrease in inflammatory markers and a reduction in oxidative stress in liver tissue. In addition, ozone exposure also promoted an increase in antioxidant enzymes. The morphological consequences of controlling these intracellular pathways were reducing the tissue inflammatory process and reducing areas of degeneration and necrosis. (4) Conclusions: Ozone exposure has a beneficial effect on models of liver injury through the decrease in oxidative stress in tissue and inflammatory markers. In addition, it regulates the Nrf2/ARE antioxidant pathway and blocks the NF-κB inflammatory pathway.

(1) Background: This study evaluated the potential of a synthetic peptide (SGHPGAMGPVGPR), identified in the bullfrog (Lithobates catesbeianus) skin, in regulating inflammation and oxidative stress using RAW 264.7 macrophages; (2) Methods: Molecular docking determined its optimal interaction with cyclooxygenase (COX-2) an enzyme related to the production of prostaglandins, which play a crucial essential role in the inflammatory response. The peptide was commercially synthesized company, and its antioxidant capacity was assessed using DPPH and FRAP assays. Cell viability, nitric oxide (NO) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione s-transferase (GST) activity, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) gene expression and cell production were additionally quantified. (3) Results: The peptide SGHPGAMGPVGPR, designated as P1, exhibited remarkable free radical scavenging capacity, antioxidant, and anti-inflammatory activities. No significant difference was observed in SOD and CAT activity in P1-treated macrophages, likely due to downregulation in the Nrf2/HO-1 pathway. Reduced GST activity was observed in these cells, which was potentially associated with TNF-α downregulation; (4) Conclusions: These findings suggest that P1 modulates the antioxidant response through pathways independent of classical antioxidant enzymes. Furthermore, decreased IL-6, COX2, and nuclear factor kappa B (NF-κB) expression was observed, indicating the involvement of a key pathway in the regulation of the OxInflammation process.

Purinergic signalling plays a central regulatory role on cell proliferation, migration, differentiation, survival, and inflammation. However, the impact of purinergic modulators-based therapies on tissue repair is still overlooked. By using a systematic review framework, we investigated the therapeutic relevance of purinergic agonists and antagonists in animal models of skin wound healing. Following PRISMA guidelines, PubMed/Medline, Scopus, Web of Science, Embase, and CINAHL databases were searched, identifying 12 in vivo preclinical studies. Risk of bias was assessed using the SYRCLE tool. Topical or oral administration of CGS-21680 (4-[{ N -ethyl-5 ’ -carbamoyladenos-2-yl}aminoethyl] phenylpropionic acid), UTP (Uridine-5'-triphosphate), NECA (5'-N-ethylcarboxamidoadenosine), ATP (adenosine triphosphate), PDRN (polydeoxyribonucleotide), ADP (Adenosine-5'-diphosphate) and TMPS (Thymidine 5'-O-monophosphorothioate) agonists stimulated wound contraction, fibroblast and keratinocyte proliferation, angiogenesis, and collagen biosynthesis. These effects were associated with activation of Nrf2 (Nuclear factor erythroid 2–related factor 2), MAPK (Mitogen-Activated Protein Kinase), and ERK/CREB pathways, inflammation and oxidative/nitrosative stress down-regulation, and increased anti-inflammatory/regulatory cytokines (IL-10, IL-13, TGF-β) and growth factors (FGF, EGF). Conversely, the purinergic antagonists DMPX (3,7-dimethyl-1-propargylxanthine), CSC (8-(3-chlorostyryl) caffeine), SUR (Suramin), ENP (enprofylline), caffeine, CLOP (clopidogrel), MRS 2179 (2′-deoxy-N6-methyladenosine-3′,5′-bisphosphate), and MRS 2395 (2-Chloro-3′,5′-O-(benzoyl-β,γ-methylene) adenosine 5′-triphosphate), as well as genetic knockout for purinergic receptors delayed wound closure by inhibiting these pathways, impairing angiogenesis, collagenogenesis, and aggravating inflammation and oxidative damage. Purinergic agonists were associated with improved wound healing through inflammatory and oxidative modulation, enhanced angiogenesis, increased cell proliferation, and accelerated wound closure, whereas antagonists or genetic deficiency of purinergic receptors impaired tissue repair. This review was registered in the PROSPERO database (CRD420251010254). Graphical abstract Overview of the effects of purinergic signalling modulation on cutaneous wound healing in murine models. Purinergic receptor activation by agonists accelerates wound closure, enhances cell proliferation and angiogenesis, and attenuates oxidative stress and pro-inflammatory cytokine production through activation of the PKA/ERK/CREB pathway. Conversely, receptor inhibition by antagonists or genetic deletion (KO) disrupts downstream signalling, resulting in delayed wound healing and increased inflammatory and oxidative damage.