Vapor of electronic cigarettes induces histopathological changes in the rat submandibular gland

The Toxicological Effects of e‐Cigarette Use in the Upper Airway: A Scoping Review

“…These included elevated levels of secreted soluble inflammatory mediators (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factorα, interferon-γ, CCL-5, CXCL-10, MCP-1, matrix metalloproteinase [MMP]-2, MMP-9, MMP-13, MUC5AC, MUC5B), increased expression of genes or proteins involved in inflammatory signaling (ERK1/2, p38, COX-2, JNK, and NF-kB), and enrichment of gene sets or pathways associated with inflammatory processes. 16,18,25,28,30,35,40,[42][43][44][45][46]49,53,62 Genotoxicity was seen primarily in the oral cavity, but also in the oropharynx and larynx, and was detected by increased DNA fragmentation, adducts, double-or single-strand breaks, appearance of micronuclei or metanuclear abnormalities, or increased expression of genes or proteins involved with DNA damage or repair pathways. 14,19,[22][23][24][25]27,32,51 Histological changes associated with acute and subchronic e-cigarette aerosol exposure in animal models were seen in the oral cavity, submandibular gland, nasal cavity, larynx, and trachea; however, the majority of these changes were considered adaptive and resolved following a recovery period.…”

“…After the removal of duplicates, 822 unique abstracts were screened, resulting in the inclusion of 53 studies (Figure 1, Table 1). 12‐64 Out of the 53 included articles, 34 (64%) analyzed the effects of e‐cigarette use on human subjects or cell lines, 16 (30%) utilized an animal model to investigate the in vivo effects of e‐cigarette aerosol exposure, and 3 (6%) studied both human and animal models. Human studies included: (1) in vitro assessments of e‐cigarette aerosol, condensate, or e‐liquid exposure on primary cultured cells or immortalized cell lines derived from upper airway tissue, or (2) clinical studies using samples obtained from current or former e‐cigarette users.…”

“…14,19,[22][23][24][25]27,32,51 Histological changes associated with acute and subchronic e-cigarette aerosol exposure in animal models were seen in the oral cavity, submandibular gland, nasal cavity, larynx, and trachea; however, the majority of these changes were considered adaptive and resolved following a recovery period. 30,31,37,47,50,52,[56][57][58][59]61,64 Persistent histological changes in the nasal cavity and larynx included: mild epithelial hyperplasia and squamous metaplasia, and mucus hypersecretion. In the submandibular gland, ductal dilation, connective tissue thickening, and epithelial degeneration with cytoplasmic vacuolization were observed.…”

“…In the submandibular gland, ductal dilation, connective tissue thickening, and epithelial degeneration with cytoplasmic vacuolization were observed. 30 Procarcinogenic features such as downregulation of tumor suppression genes were seen in normal oral cavity epithelial cells following exposure to e-cigarette aerosols or e-liquid. 15,33 Additionally, in both human oral and oropharyngeal squamous cell carcinoma cell lines, exposure to e-cigarette aerosols and flavorings led to increased cellular proliferation/survival, migration,…”

“…Mandour et al 30 Albino rats exposed to nicotine-containing e-cigarette aerosols demonstrated widening of submandibular acini and ducts along with epithelial degeneration, cytoplasm vacuolization, connective tissue septa thickening, and increased TNF-α immunostaining compared to submandibular glands from air controls.…”