Methylmercury Intoxication Promotes Metallothionein Response and Cell Damage in Salivary Glands of Rats

Abstract

Environmental and occupational mercury exposure is considered a major public health issue. Despite being well known that MeHg exposure causes adverse effects in several physiologic functions, MeHg effects on salivary glands still not completely elucidated. Here, we investigated the cellular MeHg-induced damage in the three major salivary glands (parotid, submandibular, and sublingual) of adult rats after chronic, systemic and low doses of MeHg exposure. Rats were exposed by 0.04 mg/kg/day over 60 days. After that, animals were euthanized and all three glands were collected. We evaluated total Hg accumulation, metallothionein I/II (MT I/II), α-smooth muscle actin (α-SMA), and cytokeratin 18 (CK18) immune expression. Our results have showed that MeHg is able to disrupt gland tissue and to induce a protective mechanism by MT I/II expression. We also showed that cell MT production is not enough to protect gland tissue against cellular structural damage seen by reducing marking of cytoskeletal proteins as CK18 and α-SMA. Our data suggest that chronic MeHg exposure in low-daily doses is able to induce cellular damage in rat salivary glands.

Metallothioneins and Megalin Expression Profiling in Premalignant and Malignant Oral Squamous Epithelial Lesions

“…The heterogeneity of the data collected so far suggests that MTs expression in tumorous tissue is related to tumor type and origin, differentiation status and histological grade, which all can affect tumor aggressiveness and prognosis [ 34 ]. Furthermore, MTs expression also could depend on the presence and type of exogenous carcinogenic stimuli, since many carcinogenic environmental factors, such as chronic intoxication, smoking and radiation, have been found to induce MTs in nonmalignant tissues [ 36 , 37 , 38 , 39 ]. At this point, it is worth mentioning that the expression of MTs is considered to be an adaptive response in healthy tissues, providing protection from oxidative DNA damage, thereby reducing the probability of gaining carcinogenic mutations [ 1 , 19 , 39 , 40 ].…”

Methylmercury exposure during prenatal and postnatal neurodevelopment promotes oxidative stress associated with motor and cognitive damages in rats: an environmental-experimental toxicology study

“…Thus, in a preclinical perspective, the elected MeHg dose mimics the environmental exposure faced by human populations in endemic areas of mercurial exposure, especially those dependent on fish consumption. This long-term and low-dose exposure were previously proposed by Kong et al [30] as not capable of causing visible neurological effects common to high doses of intoxication in adult animals and deeply investigated by our group in the past four years [18] , [31] , [32] , [33] , [34] , [22] . This evidence showed a reasonable proportionality between the values found in rats and humans.…”

Maternal methylmercury exposure changes the proteomic profile of the offspring’s salivary glands: Prospects on translational toxicology

“…Recent biomonitoring has revealed hair Hg PLOS ONE levels as high as 75 ppm [41][42][43], which may represent a MeHg weekly intake of 52.5 μg/kg as suggested by Crespo-Lopez [1]. Thus, the MeHg dose used in this study (40 μg/kg/BW) resembles the exposure detected in chronically exposed humans and is widely used in validated research with rats [11,23,[44][45][46] Organic Hg is mainly absorbed by the gastrointestinal tract, enters into the blood circulation, and is rapidly distributed to other tissues [6,39]. Due to its high lipophilicity, MeHg can immediately cross biological barriers; thus, MeHg consumed by pregnant women easily crosses the placenta [6,47].…”

“…Recent biomonitoring has revealed hair Hg levels as high as 75 ppm [ 41 – 43 ], which may represent a MeHg weekly intake of 52.5 μg/kg as suggested by Crespo-Lopez [ 1 ]. Thus, the MeHg dose used in this study (40 μg/kg/BW) resembles the exposure detected in chronically exposed humans and is widely used in validated research with rats [ 11 , 23 , 44 – 46 ]…”

“…The central nervous system is traditionally reported as the main target for MeHg and its neurotoxin mechanisms have been investigated by several studies [ 1 ]; however, MeHg can also damage other systems, such as immunological, renal, and cardiovascular [ 1 , 10 ]. Recent findings of our research group indicated that MeHg induced alterations in oral cell lines [ 48 ], alveolar bone [ 49 ], and salivary glands [ 11 , 44 – 46 ]. Since developing salivary glands significantly accumulate Hg [ 11 ], saliva can be potentially used as a matrix for biomonitoring environmental human exposure to MeHg [ 13 ].…”