Short-term exposure to particulate matter (PM10/2.5) from Varanasi, India led to asthma aggravation and early fibrotic changes in mice model: Insights into its regulation

Abstract

Background

Particulate matter (PM10/2.5) is a ubiquitous air pollutant with detrimental health impacts where fine particles (PM2.5) are posing serious threats to respiratory health. With potentially worse outcomes, it is silently damaging the lungs of people already suffering from respiratory diseases like asthma. The continuous exposures to poor air quality in recent years raises urgent questions for both, immediate and long-term health impacts. Both PM10/2.5 levels have surpassed the Indian National safety standards raising serious concerns about the environmental and health consequences.

Methodology

This study aimed to investigate impact of PM10/2.5 exposures on mice lungs where pathological changes in OVA-induced asthmatic mice lungs were compared with normal mice lungs. BALB/c mice were sensitized with ovalbumin (OVA, i.p), followed by OVA aerosol (1 %OVA) challenge, and later subjected to PM10/2.5 exposures (0.5 mg/kg, i.n) continuously for five consecutive days. Lung samples were assessed for oxidative stress markers (ROS and lipid peroxidation), inflammatory mediators (nitric oxide, histamine, myeloperoxidase, eosinophil peroxidase, IL-6), fibrotic markers (collagen deposition, MMP-9 activity, α-SMA expression), and histopathological changes. Dose-dependent cytotoxicity, oxidative stress induced DNA damage in human alveolar epithelial cells (A549) after PM10/2.5 exposures were thoroughly investigated. Curcumin derived from turmeric (Curcuma longa) is known anti-oxidant and anti-inflammatory molecule, was studied for its therapeutic efficacy on PM-induced asthma aggravations and fibrotic changes.

Key findings

Significant lung damage was noted after short-term PM10/2.5 exposures (5 days) with aggravated inflammatory and fibrotic changes in both, normal and asthmatic mice lungs, where PM2.5 exposure was severe. Significant morphological and histopathological changes like lung tissue remodeling, epithelial thickening, and collagen deposition was observed. Enhanced immune cell recruitment, ROS and MDA levels along with significantly decreased key antioxidant enzymes, Superoxide dismutase (SOD) and Catalase, compared to the control group were noted with reduced GSH level. Upregulated expression of NF-kB, a transcription factor after PM10/2.5 exposure was found in normal mice which was heightened in asthmatic mice. Enhanced MMP-9 activity was also confirmed by immunofluorescent detection of Alpha-smooth muscle actin (α-SMA). Curcumin, a plant-derived molecule, significantly mitigated PM2.5 exposed airway inflammation and fibrotic changes in lungs by suppressing NF-κB expression and enhancing Nrf2 level. In vitro studies validated these findings, where dose-dependent decrease in cell viability and increased in ROS level along with apoptotic changes A549 cells were observed after PM exposure. Enhanced IL-6 and PARP-1 expression confirmed progressive PM2.5 exposure induced cytotoxicity in A549 cells which was reduced after curcumin treatment.

Significance

These findings draw the attention towards detrimental impacts of poor air quality of Varanasi city with genotoxic effects which have not been reported before. Therapeutic potential of Curcumin as a natural protective agent against PM-induced respiratory damage revealed antioxidant-based interventions. It may be alarming for residents living in such polluted environments, particularly susceptible asthmatic population where silent pathological changes are in progress, thus, more detailed investigations are required along with improved air quality management policies in polluted urban areas in near future.