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Fruit derived superoxide dismutase nanozyme for sepsis-induced acute lung injury therapy

ABSTRACT: As a life-threatening infectious disease in clinics, sepsis is characterized by uncontrolled systemic inflammatory response and multi-organ damage due to the excessive production of reactive oxygen species (ROS). The lung is the most frequently affected organ that is susceptible to developing acute lung injury (ALI) with high morbidity and mortality rates. Nevertheless, there are currently no effective drugs for the treatment of ALI. Herein, we developed a natural superoxide dismutase-mimicking carbon dots (H-CDs) derived from a fruit, hawthorn, with distinctive ROS scavenging ability for ALI therapy. The carboxyl/oxygen-based groups give the generated H-CDs excellent SOD-like activity of > 9000 U mg-1 and acted as a SOD-like nanozyme in the protection of cells from oxidative damage by scavenging ROS and ameliorating the levels of pro-inflammatory factors. Importantly, H-CDs reduced lung inflammatory response, oxidative damage, and histological severity in a lipopolysaccharide (LPS)-induced ALI mice model with minimal adverse effects. Mechanistically, H-CDs protected lung tissues by activating Nrf-2/HO-1 mediated antioxidant signaling and inhibiting NF-κB-dependent inflammatory responses. Collectively, this study establishes the potential of H-CDs as a promising therapeutic agent for the treatment of ALI.

ORGANISM(S): Mus musculus

PROVIDER: GSE279500 | GEO | 2025/10/27

REPOSITORIES: GEO

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Project description:Chronic obstructive pulmonary disease (COPD) has the highest increased risk due to household air pollution arising from biomass fuel burning. However, knowledge on COPD patho-mechanisms is mainly limited to tobacco smoke exposure. In this study, a repeated direct wood smoke (WS) exposure was performed using normal- (bro-ALI) and chronic bronchitis-like bronchial (bro-ALI-CB), and alveolar (alv-ALI) lung mucosa models at air-liquid interface (ALI) to assess broad toxicological end points. The bro-ALI and bro-ALI-CB models were developed using human primary bronchial epithelial cells and the alv-ALI model was developed using a representative type-II pneumocyte cell line. The lung models were exposed to WS (10 minutes/exposure; 5-exposures over 3-days; n=6-7 independent experiments). Sham exposed samples served as control. WS composition was analyzed following passive sampling. Cytotoxicity, total cellular reactive oxygen species (ROS) and stress responsive NFkB were assessed by flow cytometry. WS exposure induced changes in gene expression were evaluated by RNA-seq (p≤0.01) followed by pathway enrichment analysis. Secreted levels of proinflammatory cytokines were assessed in the basal media. Non-parametric statistical analysis was performed. 147 unique compounds were annotated in WS of which 42 compounds have inhalation toxicity (9 very high). WS exposure resulted in significantly increased ROS in bro-ALI (11.2%) and bro-ALI-CB (25.7%) along with correspondingly increased NFkB levels (bro-ALI: 35.6%; bro-ALI-CB: 18.1%). A total of 1262 (817-up and 445-down), 329 (141-up and 188-down), and 102 (33-up and 69-down) genes were differentially regulated in the WS-exposed bro-ALI, bro-ALI-CB, and alv-ALI models respectively. The enriched pathways included the terms acute phase response, mitochondrial dysfunction, inflammation, oxidative stress, NFkB, ROS, xenobiotic metabolism of AHR, and chronic respiratory disorder. The enrichment of the ‘cilium’ related genes was predominant in the WS-exposed bro-ALI (180-up and 7-down). The pathways primary ciliary dyskinesia, ciliopathy, and ciliary movement were enriched in both WS-exposed bro-ALI and bro-ALI-CB. Interleukin-6 and tumor necrosis factor-α were reduced (p<0.05) in WS-exposed bro-ALI and bro-ALI-CB.

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Fruit derived superoxide dismutase nanozyme for sepsis-induced acute lung injury therapy

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