Airway Hyperresponsiveness, Inflammation, and Pulmonary Emphysema in Rodent Models Designed to Mimic Exposure to Fuel Oil–Derived Volatile Organic Compounds Encountered during an Experimental Oil Spill

Abstract

BACKGROUND: Fuel oil-derived volatile organic compounds (VOCs) inhalation is associated with accidental marine spills. After the Prestige petroleum tanker sank off northern Spain in 2002 and the Deepwater Horizon oil rig catastrophe in 2009, subjects involved in environmental decontamination showed signs of ongoing or residual lung disease up to 5 y after the exposure. OBJECTIVES: We aimed at investigating mechanisms driving persistent respiratory disease by developing an animal model of inhalational exposure to fuel oil-derived VOCs. METHODS: Female Wistar and Brown Norway (BN) rats and C57BL mice were exposed to VOCs produced from fuel oil mimicking the Prestige spill. Exposed animals inhaled the VOCs 2 h daily, 5 d per week, for 3 wk. Airway responsiveness to methacholine (MCh) was assessed, and bronchoalveolar lavage (BAL) and lung tissues were analyzed after the exposure and following a 2-wk washout. RESULTS: Consistent with data from human studies, both strains of rats that inhaled fuel oil-derived VOCs developed airway hyperresponsiveness that persisted after the washout period, in the absence of detectable inflammation in any lung compartment. Histopathology and quantitative morphology revealed the development of peripherally distributed pulmonary emphysema, which persisted after the washout period, associated with increased alveolar septal cell apoptosis, microvascular endothelial damage of the lung parenchyma, and inhibited expression of vascular endothelial growth factor (VEGF). DISCUSSION: In this rat model, fuel oil VOCs inhalation elicited alveolar septal cell apoptosis, likely due to DNA damage. In turn, the development of a peculiar pulmonary emphysema pattern altered lung mechanics and caused persistent noninflammatory airway hyperresponsiveness. Such findings suggest to us that humans might also respond to VOCs through physiopathological pathways different from those chiefly involved in typical cigarette smoke-driven emphysema in chronic obstructive pulmonary disease (COPD). If so, this study could form the basis for a novel disease mechanism for lasting respiratory disease following inhalational exposure to catastrophic fuel oil spills.

Inflammatory and proapoptotic effects of inhaling gasoline fumes on the lung and ameliorative effects of fenugreek seeds

“…Moreover, the present study dealt with leaded gasoline, where lead was reported to affect the immune response either in humans 11 or animals 9 . Amor-Carro et al 15 explained that lead exposure could stimulate cascade events, including oxidative stress and inflammation, accompanied by reduced immune status. Moreover, the current study exhibited a significant increase in Bax expression and a decrease in Bcl2.…”

“…Furthermore, Amor-Carro et al 15 attributed cell death to the increased formation of ROS, which leads to oxidative damage of mitochondrial DNA. Su et al 40 recommended that lipid peroxidation may serve as a common mediator of apoptosis in response to toxicants and pathological conditions.…”

“…In turn, the mixture of both VOCs and leaded compounds in gasoline may be a potent source of reactive oxygen species (ROS) that may stimulate the signaling cascades of the inflammatory process. The latter may act as a mediator of adverse health effects related to several pathogenic mechanisms including apoptosis and fibrosis 15 .…”

Toxicological Effects of Inhaled Crude Oil Vapor

“…Recently, investigations [ 92 , 111 – 118 ] were conducted to evaluate the toxicity of inhaled COV generated from Deep Water Horizon (DWH) surrogate crude oil in a rat model to gain a greater understanding of the adverse health effects of COV inhalation in upstream petroleum workers [ 49 , 74 , 119 ]. The DWH surrogate crude oil provided by British Petroleum (BP) Exploration and Production, Inc., similar to the oil associated with the 2010 Deepwater Horizon spill from the Macondo Well in Mississippi Canyon Block 252, was characterized in McKinney et al [ 95 ].…”