Mercury is a highly toxic heavy metal with significant public health and safety implications worldwide (Ishitob et al. 2010; Azevedo et al. 2012; Pizzorno 2011; Bernhoft 2012; Chakraborty 2017). Mercury is commonly found in nature in many different forms (Zahir et al. 2005; Bernhoft 2012; Zhu et al. 2020). Inorganic mercury includes metallic mercury, mercury vapor (Hg0), and mercurous (Hg+ 2) or mercuric salts, while the organic form of mercury includes compounds containing carbon atoms such as methyl, ethyl, or phenyl groups (Costa et al. 2020). All forms of mercury compounds mentioned earlier can be found, and chemically interchangeable, in the environment (Graeme and Pollack 1998).
According to the World Health Organization (WHO), most human exposure to mercury occurs through the inhalation of elemental mercury vapor via occupational or dental amalgam exposure (WHO 1991; Zhu et al. 2020). The ingestion of seafood contaminated with organic mercury has been reported as another major route via which people are exposed to mercury (Zhu et al. 2020). Although mercury is present naturally in the environment, recent human industrial activities have resulted in the dangerous accumulation of more mercury in the land, water, and food supplies (Clarkson 2008; Zhu et al. 2020). This accumulation of mercury in the environment carries grave health risks and consequences. The most infamous case of mercury poisoning of the 20th century is the “Minamata disease” incident, with the first cases noted in 1956 (Harada 1995). Industrial waste containing methylmercury was being released into Minamata Bay in Japan by a Japanese chemical factory, which then reached the locals through contaminated fish as food. Thousands of locals have been affected since then, and even babies born in the 1960s-1970s to mothers that have been exposed to the contaminated fish were noted to have brain damage, mental retardation, and a variety of other diseases (Graeme and Pollack 1998). Industrial regulations have been put into action ever since recognizing the toxic nature of mercury and its ability to cross the blood-brain barrier. However, industrial activities such as coal combustion still produce high mercury levels disposed of in the atmosphere, land, and water (Streets et al. 2018).
The pathogenesis of mercury poisoning is often multifaceted as it manifests in many forms and can impact all body systems depending on the underlying pathways and enzymes affected. This vast pathogenic potential is due to the tendency of mercury to bind to sulfur groups (Graeme and Pollack 1998), which are an essential component of the chemical structure of cellular proteins, enzymes, channels, and pumps, thereby disrupting their physiological function and inducing pathological change. One molecular effect of mercury is the inhibition of vascular endothelial enzymes such as Na/K-ATPase and Ca2-ATPase, leading to disrupted vascular reactivity (Vassallo et al. 2011). Another effect that mercury has on the body vasculature is mercury-induced nitric oxide (NO) inhibition, as a result of endothelial nitric oxide synthase (NOS) pathway inhibition (Omanwar et al. 2013). This leads to the disruption of normal vasodilation and vasoconstriction of the vasculature. Mercury has also been shown to increase the production of reactive oxygen species (ROS), which in turn led to the inactivation of numerous enzymes such as Paraoxonase, Glutathione peroxidase, Phospholipase D, and Mitogen-activated protein kinases (MAPKs) (Azevedo et al. 2012; Vassallo et al. 2011; Haase et al. 2010). MAPKs are extremely important to the functioning of the immune system, as they play an essential role in T-cell activation. Haase et al. (2010) demonstrated that mercury binding to MAPKs did not significantly result in dysfunction of MAPKs, but the overproduction of ROS triggered by the mercury was the cause of the MAPKs dysfunction. Mercury has also been associated with developing clinical manifestations of metabolic syndrome such as obesity, insulin resistance, and hypertension (Tinkov et al. 2015). Tinkov et al. (2015) proposed that mercury affects the renin-angiotensin-aldosterone system (RAAS), leading to hypertension and altering β-cell functionality leading to insulin resistance.
The IL-1 cytokines act to regulate pro-inflammatory mediators in tissue injury (Weber et al. 2010). The effect of mercury on IL-1 expression has been demonstrated in some studies, but the results have been inconclusive (Zdolsek et al., 1994; Batista-Duharte et al., 2018). IL-1 production has been shown to increase due to the presence of mercury in the tissue (Zdolsek et al., 1994), while in another study, mercury was shown to have the opposite effect and reduce IL-1 expression (Batista-Duharte et al., 2018).
Elemental mercury vapor inhalation has been shown to lead to direct lung tissue injury, capillary destruction, pulmonary edema, and eventually fibrosis (Asano et al. 2000). Acute severe exposure to elemental mercury vapor has been reported to lead to fatality as a result of pulmonary insufficiency and acute renal failure (Asano et al. 2000). Generally, mercury exposure is chronic at a low dosage resulting in subtle toxic manifestations characterized by loss of appetite, weakness, malaise, loss of weight, and gastrointestinal upset (Bernhoft 2012; Zhu et al. 2020). However, in the acute form, more severe manifestations related to the immune system, gastrointestinal tract, renal, cardiopulmonary, and nervous systems have been reported (Houston 2011; Bernhoft 2012). Rapid recognition of mercury poisoning and its complications is critical in avoiding poor patient outcomes and lifesaving. The clinical management of mercury vapor poisoning revolves around maintaining ventilation, decontamination, chelation, and treating complications (Rafati-Rahimzadeh et al. 2014). In severe acute cases with high plasma concentrations of mercury, plasma exchange can be used as well (Russi and Marson 2011).
To our knowledge, no recent scientific reports are documenting the effects of exposure to elementary mercury vapor on various blood gas parameters and underlying pulmonary lesions that might explain possible acid-base alterations associated with inhalation of mercury vapor. Therefore, this study was designed to investigate the toxic effects of elemental mercury vapor on various arterial blood gas parameters and to determine the possible underlying pulmonary pathology that might lead to acid-base alterations using Sprague-Dawley rats.