UC Davis

The impact of naphthalene (NA), an abundant volatile polycyclic aromatic hydrocarbon commonly found in wildfire smoke, cigarette smoke, and vehicle exhaust, is both site- and species-specific. NA toxicity in the lungs is well-defined to cause a dose-dependent Club cell toxicant in the conducting airway epithelium of mice, regardless of exposure route. Endogenous antioxidant, glutathione (GSH), detoxifies NA by creating a NA-GSH conjugate. Although NA and GSH are well studied, few scientists has examined exogenous antioxidants in this process and their ability to limit NA induced toxicity in the lungs. Ergothioneine (ET), a dietary antioxidant abundant in mushrooms, has been reported to protect cells from oxidant stress as a scavenger for free radicals and function as an immunoregulator in the presence of oxidative stress in several systems. ET transporter (SLC22A4) is the main regulator for the uptake of cellular ET and is known to concentrate in areas that experience high levels of oxidative stress. The overall aim of this dissertation is to understand the impact of ET pretreatment in NA exposed lungs of young (1 month), adult (2-3 months), and elderly mice (12-18 months). To test if ET pretreatment will protect the lung from NA toxicity, the mice will be treated with an oral dosage of 70 mg/kg of ET, or saline, daily for 5 days, and on day 8 mice are injected with NA or corn oil alone. At 2 and 24 hours post NA injection, the lungs, liver, and blood will be collected and processed for further analysis measuring oxidative stress and assessing detoxification. Chapter Two in this dissertation evaluates the impact of ET pretreatment and NA toxicity between juveniles and adult mice; Chapter Three examines the temporal pattern of molecular changes at 2 and 24 hours post NA exposure; and lastly, Chapter Four explores the impact of ET and NA in geriatric mice. This is the first time geriatric mice have been studied for NA toxicity. Collectively, this dissertation aims to advance our understanding of the mechanisms of NA toxicity, normal cellular mechanism of protection, and the role of a potential dietary antioxidant, ET, in the lung, liver, and blood, across the life span.