Table 2.
The impact of e-cigarette liquid exposure on animal models (in vivo studies).
| Animals | Characteristic of E-Liquid | Action | Ref. | |
|---|---|---|---|---|
| 1. | C57BL/6J mice | Base: PG:VG Nicotine: 33 mg/mL Flavor: flavorless |
Decreased: innate immunity against viral pathogens in resident macrophages Increased: surfactant-associated phospholipids in the airway, lipid deposition Altered: lung lipid homeostasis in alveolar macrophages and epithelial cells, phospholipids in alveolar macrophages |
[146] |
| 2. | C57BL/6 mice | Base: PG:VG (50%/50%) Nicotine: 18 mg/mL Flavor: tobacco |
Increased: bronchoalveolar lavage fluid (BALF) cellularity, Muc5ac production, BALF and lung oxidative stress markers | [140] |
| 3. | C57BL/6 mice | Base: unknown Nicotine: 13 mg/mL Flavor: tobacco |
Decrease: hippocampal gene expression of Ngfr and Bdnf, serum levels of cytokines IL-1β, IL-2, and IL-6 Increased: expression of Iba-1, a specific marker of microglia, in the cornus ammonis 1 region of the hippocampus |
[147] |
| 4. | C57BL/6 mice | Base: PG:VG (50%/50%) Nicotine: 24 mg/mL Flavor: flavorless |
Decreased: weight gain Increased: angiogenesis in mouse heart tissue, endothelial cell marker CD31 and CD34, collagen content in heart tissue |
[148] |
| 5. | C57BL/6J mice | Base: unknown Nicotine: 18 mg/mL Flavor: strawberry |
Increased: IL-1β release | [125] |
| 6. | C57BL/6J mice | Base: PG:VG Nicotine: 16 mg/mL Flavors: tobacco, menthol fruit, cinnamon, candy |
Decreased: lung glutathione levels Increased: proinflammatory cytokines |
[98] |
| 7. | C57BL/6J mice | Base: PG 00% Nicotine: 2.4% Flavor: flavorless |
Increased: activity in the zero maze and open field tests | [149] |
| 8. | C57BL/6J mice | Base: PG:VG (70%/30%) Nicotine: 18 mg/mL Flavor: menthol |
Increased: platelets hyperactivation with enhanced aggregation, dense and α granule secretion, activation of the αIIbβ3 integrin, phosphatidylserine expression, and Akt and ERK activation Decreased: thrombosis occlusion and bleeding times |
[150] |
| 9. | C57BL/6 mice | Base: PG:VG Nicotine: 4% by weight Flavors: different (nonmenthol) flavor mixtures |
Altered: minimal squamous metaplasia in laryngeal epiglottis, and histiocytic infiltrates in the lung, genes expression | [151] |
| 10. | C57BL/6 mice | Base: PG:VG (50%/50%) Nicotine: 24 mg/mL Flavors: flavorless |
Decreased: dopamine concentration in the striatum and GABA in frontal cortex Increased: glutamate concentration in the striatum and glutamine in the frontal cortex and striatum |
[152] |
| 11. | C57BL/6 mice | Base: unknown Nicotine: 18 mg/mL Flavor: cappuccino |
Increased: arterial stiffness Decreased: the maximal aortic relaxation to methacholine |
[153] |
| 12. | C57BL/6J mice | Base: unknown Nicotine: 1.8% Flavor: menthol |
Decreased: pulmonary bacterial clearance, phagocytosis by alveolar macrophages Increased: oxidative stress, intranasal infection with Streptococcus pneumonia, lung viral titers and virus-induced illness and mortality in response to Influenza A virus infection |
[141] |
| 13. | Pregnant C57BL/6J mice | Base: PG:VG (55%/45%) Nicotine: 24 mg/mL Flavor: flavorless |
Impair embryo implantation Altered: integrin, chemokine, and JAK signaling pathways |
[154] |
| 14. | Pregnant C57BL/6 mice | Base: unknown Nicotine: 13–16 mg/mL Flavor: tobacco |
Alerted: transcriptome in frontal cortex in both offspring and treatment groups | [155] |
| 15. | Neonatal C57BL/6J mice | Base: PG 100% Nicotine: 1.8% Flavor: flavorless |
Decreased: weight gain Increased: cotinine levels Altered: lung growth |
[144] |
| 16. | C57BL/6 mice; CD-1 mice | Base: PG:VG (50%/50%) Nicotine: 24 mg/mL Flavor: flavorless |
Decreased: renal filtration, heart rate Increased: circulating proinflammatory and pro-fibrotic proteins, fibrosis in kidneys, heart and liver, blood pressure Altered: gene expression–activation of pro-fibrotic pathway, cardiovascular function |
[111] |
| 17. | Balb/c mice | Base: PG:VG Nicotine: 12 mg/mL Flavor: tobacco |
Decrease: parenchymal lung function at both functional residual capacity and high transrespiratory pressures | [156] |
| 18. | Balb/c mice | Base: unknow Nicotine: 16.8 mg/day Flavor: flavorless |
Increased: brain cotinine and nicotine levels, urine cotinine levels, α4β2 nicotinic acetylcholine receptors in different brain areas | [157] |
| 19. | Balb/c mice | Base: unknown Nicotine: 16 mg/mL Flavors: flavorless |
Decreased: asthmatic airway inflammation and airway hyperresponsiveness Increased: infiltration of inflammatory cells into airways from blood, cytokines such as interleukin (IL)-4, IL-5 and IL-13 release, and ovalbumin -specific IgE production |
[32] |
| 20. | Balb/c mice | Base: PG:VG (50%/50%) Nicotine: 12 mg/mL Flavor: Black Licorice, Kola, Banana Pudding, Cinnacide |
Decreased: airway inflammation Increased: peripheral airway hyperresponsiveness, soluble lung collagen Heterogeneous effects on features of allergic airways disease |
[158] |
| 21. | Pregnant Balb/C mice | Bae: unknown Nicotine: 18 mg/mL Flavor: tobacco |
Decrease: global DNA methylation, Aurora Kinase (Aurk) A and AurkB gene expression and a reduction in neuronal cell numbers in the cornu ammonis 1 region of the dorsal hippocampus in offspring from mothers switching to e-cigarettes | [159] |
| 22. | Pregnant Balb/c mice | Base: PG:VG (50%/50%) Nicotine: 18 mg/mL Flavor: tobacco |
Increased: markers of oxidative stress, inflammation, and fibrosis in the adult offspring | [160] |
| 23. | Pregnant Balb/c mice | Base: unknown Nicotine: 18 mg/mL Flavor: flavorless |
Decreased: body fat in offspring Increased: mRNA expression of brain NPY and iNOS in offspring |
[161] |
| 24. | Pregnant Balb/C mice | Base: PG:VG (50%/50%) Nicotine: 18 mg/mL Flavor: tobacco |
Decreased: anxiety, and hyperactivity Increased: global DNA methylation in the brains Altered: genes associated with modulating neurological activity Deficits in short-term memory in offspring |
[145] |
| 25. | Pregnant Balb/c mice | Base: PG:VG (50%/50%) Nicotine: 18 mg/mL Flavor: tobacco |
Increased: IL-1β, IL-6, and TNF-α release in the mother lung, TNF-α protein levels in adult offspring Decreased: IL-1β level in adult offspring Altered: global DNA methylation |
[162] |
| 26. | CD1 mice | Base: unknown Nicotine: 24 mg/mL Flavor: tobacco |
Increased: nasal platelet-activating factor receptor (PAFR) expression and nasopharyngeal pneumococcal colonization | [126] |
| 27. | CD1 mice | Base: PG:VG (50%/50%) Nicotine: 24 mg/mL Flavor: flavorless |
Decreased: glutamate transporter-1 expression in striatum, cystine/glutamate antiporter in striatum and hippocampus Increased: expression of alpha-7 nicotinic acetylcholine receptor (α-7 nAChR), which regulates glutamate release in frontal cortex and stratum, level of nicotine and cotinine in frontal cortex |
[163] |
| 28. | CD-1 mice | Base: PG:VG, PG 100% Nicotine: 0.6%, 1.8%, 14–24 mg/mL Flavors: flavorless, Treasury, Highlander Grog, California Blues, Pure smoke |
Increased: acute phase reactant in serum Altered: inflammatory markers within the airways |
[137] |
| 29. | ICR mice | Base: VG 100% Nicotine: 0.5 and 5 mg/mL Flavor: flavorless |
Decrease: in the grip strength and swimming time of the mice, glycogen storage in liver and muscle | [164] |
| 30. | FVBN mice | Base; PG:VG (50%/50%) Nicotine: 24 mg/mL Flavor: flavorless |
Decreased: DNA-repair activity and repair proteins XPC and OGG1/2 in the lung Increased: DNA damage in the lung, bladder, and heart |
[75] |
| 31. | FVB/N mice | Base: PG:VG (50%/50%) Nicotine: 36 mg/mL Flavor: flavorless |
Increased: lung adenocarcinomas and bladder urothelial hyperplasia cases | [165] |
| 32. | A/J mice | Base: PG:VG (50%/50%) Nicotine: 18 mg/mL Flavor: flavorless |
Increased: airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression | [100] |
| 33. | C57BL/6 mice; Apolipoprotein E knockout [ApoE−/−] mice |
Base: unknown Nicotine: 2.4% Flavor: tobacco |
Decreased: body weight, food intake Increased: Plasma nicotine and cotinine levels, locomotion |
[166] |
| 34. | Apolipoprotein E knockout [ApoE−/−] mice | Base: unknown Nicotine: 2.4% Flavor: flavorless |
Decreased: left ventricular fractional shortening and ejection fraction Increased: oxidative stress, mitochondrial DNA mutations, atherosclerotic lesions Altered: genes associated with metabolism, circadian rhythm, inflammation, ultrastructural abnormalities indicative of cardiomyopathy |
[167] |
| 35. | Apolipoprotein E knockout [ApoE−/−] mice on a western diet | Base: unknown Nicotine: 2.4% Flavor: flavoreless |
Increased: hepatic lipid accumulation, oxidative stress, hepatic triglyceride levels, hepatocyte apoptosis Altered: gene expression (including genes associated with lipid metabolism, cholesterol biosynthesis, and circadian rhythm) |
[168] |
| 36. | Apolipoprotein E knockout [ApoE−/−] mice | Base: unknown Nicotine: 2.4% Flavor: tobacco |
Decreased: NAD+/NADH ratio, sirtuin 1 (SIRT1) Increased: DNA damage (apurinic/apyrimidinic sites), oxidative stress in hepatic cells, poly (ADP ribose) polymerase (PARP1) activity, mitochondrial DNA mutations, and PTEN-induced kinase 1 (PINK1), vacuolization of the mitochondria and a reduction in cellular organelles in hepatocytes |
[169] |
| 37. | DJ-1 knockdown mice |
Base: Unknown Nicotine: 24 mg/mL Flavor: flavorless |
Altered: regulation of oxidative phosphorylation complexes | [110] |
| 38. | Sprague Dawley rats | Base: unknown Nicotine: 12 and 24 mg/mL Flavor: tobacco |
Increased: necrosis in dorsal skin flaps | [170] |
| 39. | Sprague Dawley rats | Base: PG:VG Nicotine: 18 mg/mL Flavor: red fruits |
Increased: phase-I carcinogen-bioactivating enzymes activity, oxygen free radical production, DNA oxidation, DNA damage at chromosomal and gene level | [142] |
| 40. | Wistar rats | Base: PG:VG (50%/40%) Nicotine: 18 mg/mL Flavor: tobacco |
Decreased: sperm vitality, sperm count in the cauda epididymis Increased: morphologically abnormal spermatozoa, myeloperoxidase granules–inflammatory state Altered: semen parameters, redox status |
[171] |
| 41. | Wistar rats | Base: PG:VG (50%/40%) Nicotine: 18 mg/mL Flavor: tobacco |
Decreased: total protein content (superoxide dismutase, catalase and glutathione-S-transferase), cell viability Increased: malondialdehyde content, lipid peroxidation, oxidative stress, inflammatory cells infiltration, oxidative tissue injuries |
[172] |
| 42. | Wistar rats | Base: PG:VG (50%/40%) Nicotine: 18 mg/mL Flavor: tobacco |
Decreased: uric acid and mainly urea, superoxide dismutase and catalase activities Increased: total protein and sulfhydryl content, cells with reduced and dark nuclei located in the renal collecting ducts |
[173] |
| 43. | Wistar rats | Base: PG:VG (50%/40%) Nicotine: 18 mg/mL Flavor: tobacco |
Decreased: sperm density and viability, testicular lactate dehydrogenase activity, testosterone level, cytochrome P450 side-chain cleavage, 17 beta-hydroxysteroid dehydrogenase mRNA level Increased: antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione-S-transferase, sulfhydryl group content Altered: testis tissue—germ cells desquamation, disorganization of the tubular contents of testis and cell deposits in seminiferous tubules |
[174] |