Environmental Quinones and their Impact on Human Red Blood Cells: Mechanism and Pathophysiological Implications

Neha, . (2026) Environmental Quinones and their Impact on Human Red Blood Cells: Mechanism and Pathophysiological Implications. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Neha (20RS080)) 20RS080.pdf - Submitted Version Restricted to Repository staff only Download (8MB)

Abstract

Air pollution, particularly exposure to fine particulate matter (PM2.5), is a major global risk factor associated with several health hazards, including asthma, dementia, cardiovascular dysfunction, and hypoxia-related disorders. However, the molecular mediator for these adverse effects remains poorly defined. Quinones, prevalent constituents of PM2.5, are suspected mediators of these health effects. Human exposure to quinones primarily occurs through the inhalation of polluted air and tobacco smoke, and their biological relevance is supported by the presence of p-benzoquinone adducts in human lens proteins, serum albumin, and hemoglobin in smokers. Yet, the direct impact of these reactive electrophiles on human red blood cells (RBCs), the first cells to encounter them in circulation, has not been thoroughly explored. We investigated how environmentally relevant quinones compromise the biochemical, structural, and functional integrity of human RBCs using an integrated approach that combines redox biochemistry, fluorescence and spectroscopic analyses, scanning electron microscopy, metabolomics, lipidomics, and advanced mass spectrometry. Our findings demonstrate that quinones induce profound oxidative stress through glutathione depletion and ROS generation, promote hemoglobin oxidation and destabilization, reduce oxygen-binding capacity, remodel membrane proteins and lipids, decrease membrane fluidity, and impair cellular deformability. These alterations collectively disrupt RBC homeostasis, creating conditions that may promote hypoxia, increased blood viscosity, impaired capillary transit, and vascular obstruction. Additionally, we validated a GC-MS method for the quantitative determination of these quinones in human plasma and saliva, providing a platform for biomonitoring exposure. Overall, this work establishes a comprehensive molecular framework linking environmental quinone exposure to RBC dysfunction, offering mechanistic insight into how air pollution and cigarette smoke may contribute to vascular and hypoxia-related pathologies.

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