Abstract
Chronic alcohol consumption has a negative impact on the submandibular and parotid salivary glands. The aim of this study was to study changes in morphological structures and to determine the relationship with the levels of neurotransmitters in the bioamine-containing structures of submandibular glands (SMGs) and parotid glands (PGs) in rats with prolonged alcohol intoxication. In this study, sexually mature male albino Wistar rats consumed 20% ethanol (6.9 g/kg/day) for 180 consecutive days. PGs and SMGs were collected for morphometric and luminescence-histochemical analyses (nonparametric Mann–Whitney U-test, p < 0.05). PGs exposed to ethanol for 180 days showed a change in the shape of the acini and secretory cells that formed them, uneven expansion of the interlobular excretory ducts, and moderate fatty infiltration of the stroma. SMGs exposed to ethanol for 180 days showed changes in acinar cells, intercalated and striated ducts, fatty infiltration, mild atrophy, and stromal edema. The number of mast cells in PGs and SMGs and their degranulation index doubled after exposure to ethanol, and the cells were highly active. With prolonged 180-day alcohol intoxication, there was a gradual increase in the histamine level in the acini of the salivary glands, a decrease in the serotonin level and catecholamines in all structures of the salivary glands, and a gradual decrease in the activity of monoamine oxidase to the level of control. Therefore, prolonged 180-day ethanol intoxication can cause negative morphological changes and functional differences in the activity of monoamine oxidase and biogenic amines in the SMGs and PGs of rats.
Similar content being viewed by others
Availability of data and material
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
References
Aimbetov TD, Aliyeva MZh (2017) The reaction of mast cell in the parotid gland on chain alcohol intoxication. Eur J Nat Hist 2:3–6
Allen CD, Lee S, Koob GF, Rivier C (2011) Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats. Brain Behav Immun Suppl 1(Suppl 1):S50-60. https://doi.org/10.1016/j.bbi.2011.01.016
Artishevsky AA, Leontyuk AA, Sluka AS (1999) Histology with the technique of histological studies. Minsk
Balakleevsky AI (1980) Method for determining the activity of monoamine oxidases in biological material. Patent for an invention G01N21/24. Bulletin 21
Bartko J, Gludovacz E, Petroczi K, Borth N, Jilma B, Boehm T (2016) Recombinant human diamine oxidase activity is not inhibited by ethanol, acetaldehyde, disulfiram, diethyldithiocarbamate or cyanamide. Alcohol 54:51–59. https://doi.org/10.1016/j.alcohol.2016.06.001
Bell RL, Hauser S, Rodd ZA, Liang T, Sari Y, McClintick J, Rahman S, Engleman EA (2016) A genetic animal model of alcoholism for screening medications to treat addiction. Int Rev Neurobiol 126:179–261. https://doi.org/10.1016/bs.irn.2016.02.017
Bertl K, Haririan H, Laky M, Matejka M, Andrukhov O, Rausch-Fan X (2012) Smoking influences salivary histamine levels in periodontal disease. Oral Dis 18:410–416. https://doi.org/10.1111/j.1601-0825.2011.01891.x
Björklund A, Ehinger B, Falck BZ (1972) Analysis of fluorescence excitation peak ratios for the cellular identification of noradrenaline, dopamine or their mixtures. J Histochem Cytochem 20:56–64. https://doi.org/10.1177/20.1.56
Björklund A, Falck B, Lindvall O, Svensson LA (1973) New aspects on reaction mechanisms in the formaldehyde histofluorescence method for monoamines. J Histochem Cytochem 21:17–25. https://doi.org/10.1177/21.1.17
Chan JM (2019) 4 - Drug metabolism and pharmacogenetics. Pharmacol Physiol Anesth (2nd Edition) 1:70–90. https://doi.org/10.1016/b978-0-323-48110-6.00004-1
Close B, Banister K, Baumans V, Bernoth EM, Bromage N, Bunyan J, Erhardt W, Flecknell P, Gregory N, Hackbarth H, Morton D, Warwick C (1996) Recommendations for euthanasia of experimental animals: part 1. DGXI of the European Commission. Lab Anim 30(4):293–316. https://doi.org/10.1258/002367796780739871
Close B, Banister K, Baumans V, Bernoth EM, Bromage N, Bunyan J, Erhardt W, Flecknell P, Gregory N, Hackbarth H, Morton D, Warwick C (1997) Recommendations for euthanasia of experimental animals: part 2. DGXT of the European Commission. Lab Anim 31(1):1–32. https://doi.org/10.1258/002367797780600297
Conti P, Caraffa A, Tetè G, Gallenga CE, Ross R, Kritas SK, Frydas I, Younes A, Emidio PD, Ronconi G (2020) Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19. J Biol Regul Homeost Agents 34(5):1629–1632. https://doi.org/10.23812/20-2EDIT
Cross SAM, Ewen SWB, Rost FWD (1971) A study of the methods a vailable for cytochemical localisation of histamine by fluorescence induced with ophtaldehyde or acetaldehyde. Histochem J 3:471–476
D’hooghe MB, De Keyser J (2012) Associations of alcohol consumption with clinical and MRI measures in multiple sclerosis. Expert Rev Neurother 12:657–660. https://doi.org/10.1586/ern.12.44
Da Silva EZM, Jamur MC, Oliver C (2014) Mast cell function: a new vision of an old cell. J Histochem Cytochem 62:698–738. https://doi.org/10.1369/0022155414545334
DeBruin EJ, Gold M, Lo BC, Snyder K, Cait A, Lasic N, Lopez M, McNagny KM, Hughes MR (2015) Mast cells in human health and disease. Methods Mol Biol 1220:93–119. https://doi.org/10.1007/978-1-4939-1568-2_7
de Oliveira PA, de Pizzol-Júnior JP, Longhini R, Sasso-Cerri E, Cerri PS (2017) Cimetidine reduces interleukin-6, matrix metalloproteinases-1 and -9 immunoexpression in the gingival mucosa of rat molars with induced periodontal disease. J Periodontol 88(1):100–111. https://doi.org/10.1902/jop.2016.160132
Epsley S, Tadros S, Farid A, Kargilis D, Mehta S, Rajapakse CS (2021) The effect of inflammation on bone. Front Physiol 11:511799. https://doi.org/10.3389/fphys.2020.511799
Erjaveca GN, Hodzic JB, Repovecki S, Perkovic MN, Uzun S, Kozumplik O, Tudor L, Mimica N, Strac DS, Pivac N (2021) Alcohol related phenotypes and platelet serotonin concentration. In Press, Journal Pre-proof, Alcohol Available online. https://doi.org/10.1016/j.alcohol.2021.09.001
Falk B (1962) Fluorescence of catecholamines and related compounds condensed with formaldehyde. J Histochem Citochem 10:348–354
Federal Law of the Russian Federation “On the protection of animals from cruelty” dated 01.12.1999 No. 4679-II GD (1999) [In Russian]
Gazimagomedova IK (2017) Histological technique. Study guide. 2017. Makhachkala, Dagestan
Gordova VS, Ivanova EP, Sergeeva VE (2018) Properties of toluidine blue stained mast cells in the experiment with the intake of soluble silicon. Vestnik IKBFU Natural and Medical Sciences 2:97–104 [In Russian]
Groeger M, Spanier G, Wolf M, Deschner J, Proff P, Schröder A, Kirschneck C (2020) Effects of histamine on human periodontal ligament fibroblasts under simulated orthodontic pressure. PLoS ONE 15(8):e0237040. https://doi.org/10.1371/journal.pone.0237040
Guan G, Won J, Mei L, Polonowita A (2020) Extensive adipose replacement of the parotid glands: an unusual presentation of sialadenosis. A case report and literature review. Oral Surg 13:41–47. https://doi.org/10.1111/ors.12442
Guidelines for accommodation and care of animals. Environment, housing and management (2016) Russia, Moscow
Hughes MR, McNagny KM (2015) Mast cells. Methods Mol Biol. https://doi.org/10.1007/978-1-4939-1568-2
Khairnar MR, Wadgave U, Khairnar SM (2017) Effect of alcoholism on oral health: a review. J Alcohol Drug Depend 5:266. https://doi.org/10.4172/2329-6488.1000266
Kim K (2012) Neuroimmunological mechanism of pruritus in atopic dermatitis focused on the role of serotonin. Biomol Ther (seoul) 20:506–512. https://doi.org/10.4062/biomolther.2012.20.6.506
Krokhina EM, Aleksandrov PN (1969) Sympathetic (adrenergic) component of the effector innervation of the heart muscle. Cardiology 9:97–102 [In Russian]
Mendes LO, Amorim JPA, Teixeira GR, Chuffa LGA, Fioruci BA, Pimentel TA, de Mello Jr W, Padovani CR, Pereira S, Martinez M, Pinheiro PFF, Oliani SM, Martinez FE (2011) Mast cells and ethanol consumption: interactions in the prostate, epididymis and testis of UChB rats. Am J Reprod Immunol 66:170–178. https://doi.org/10.1111/j.1600-0897.2010.00958.x
Müller CP, Schumann G, Kornhuber J, Kalinichenko LS (2020) The role of serotonin in alcohol use and abuse. Handb Behav Neurosci 31:803–827. https://doi.org/10.1016/B978-0-444-64125-0.00041-4
Nasehi M, Zamanparvar M, Ebrahimi-Ghiri M, Zarrindast M-R (2016) Modulation of cannabinoid signaling by amygdala α2-adrenergic system in fear conditioning. Behav Brain Res 300:114–122. https://doi.org/10.1016/j.bbr.2015.12.017
Order of the Ministry of Health of the USSR of 08/12/1977 No. 755 (1977) On measures to further improve organizational forms of work with the use of experimental animals. [In Russian]
Panula P (2020) Histamine, histamine H 3 receptor, and alcohol use disorder. Br J Pharmacol 177(3):634–641. https://doi.org/10.1111/bph.14634
Panula P, Nuutinen S (2011) Histamine and H3 receptor in alcohol-related behaviors. J Pharmacol Exp Ther 336(1):9–16. https://doi.org/10.1124/jpet.110.170928
Prestifilippo JP, Fernández-Solari J, Lamas DJM, Rios CE, Mohn C, Perazzo JC, Rivera ES, Elverdin JC, Medina VA (2016) Pharmacological targeting of histamine H4 receptor in periodontal disease. Oral Dis 22(5):423–429. https://doi.org/10.1111/odi.12467
Ribatti D, Tamma R, Annese T (2020) Mast cells and angiogenesis in multiple sclerosis. Inflamm Res 69:1103–1110. https://doi.org/10.1007/s00011-020-01394-2
Schiff HC, Johansen JP, Hou M, Bush DEA, Smith EK, Klein JE, LeDoux JE, Sears RM (2017) β-Adrenergic receptors regulate the acquisition and consolidation phases of aversive memory formation through distinct, temporally regulated signaling pathways. Neuropsychopharmacology 42(4):895–903. https://doi.org/10.1038/npp.2016.238
Schneider AM, Simson PE, Daimon CM, Mrozewski J, Vogt NM, Keefe J, Kirby LG (2014) Stress-dependent opioid and adrenergic modulation of newly retrieved fear memory. Neurobiol Learn Mem 109:1–6. https://doi.org/10.1016/j.nlm.2013.11.013
Schramm MJW, Everitt BJ, Milton AL (2015) Bidirectional modulation of alcohol-associated memory reconsolidation through manipulation of adrenergic signaling. Neuropsychopharmacology 41:1103–1111. https://doi.org/10.1038/npp.2015.248
Stegaev V, Nies AT, Porola P, Mieliauskaite D, Sánchez-Jiménez F, Urdiales JL et al (2013) Histamine transport and metabolism are deranged in salivary glands in Sjogren’s syndrome. Rheumatology (Oxford) 52:1599–1608. https://doi.org/10.1093/rheumatology/ket188
Tanaka S (2020) Phenotypic and functional diversity of mast cells. Int J Mol Sci 21(11):3835. https://doi.org/10.3390/ijms21113835
Trakhtenberg IM, Sova RE, Sheftel VO, Onikienko FA (1991) The problem of the norm in toxicology (modern concepts and methodological approaches, basic parameters and constants). Moscow [In Russian]
Tripathi AC, Upadhyay S, Paliwal S, Saraf SK (2018) Privileged scaffolds as MAO inhibitors: retrospect and prospects. Eur J Med Chem 145:445–497. https://doi.org/10.1016/j.ejmech.2018.01.003
Trovero F, David S, Bernard P, Puech A, Bizot J-C, Tassin J-P (2016) The combination of marketed antagonists of α1b-Adrenergic and 5-HT2A receptors inhibits behavioral sensitization and preference to alcohol in mice: a promising approach for the treatment of alcohol dependence. PLoS One 11(3):e0151242. https://doi.org/10.1371/journal.pone.0151242
Tsirkin VI, Trukhin AN, Trukhina SI (2020) Choline and monoaminergic transmitter systems in health and disease. Kirov [In Russian]
Varricchi G, de Paulis A, Marone G, Galli SJ (2019) Future needs in mast cell biology. Int J Mol Sci 20(18):4397. https://doi.org/10.3390/ijms20184397
Vazey EM, den Hartog CR, Moorman DE (2018) Central noradrenergic interactions with alcohol and regulation of alcohol-related behaviors. Handb Exp Pharmacol 248:239–260. https://doi.org/10.1007/164_2018_108
Wang G-D, Wang X-Y, Zou F, Qu M, Liu S, Fei G et al (2013) Mast cell expression of the serotonin1A receptor in guinea pig and human intestine. Am J Physiol Gastrointest Liver Physiol 304:G855-863. https://doi.org/10.1152/ajpgi.00421.2012
Yakovleva LM, Lubovtseva LA (2013) Dynamics of neurotransmitters in the structures of the rat jejunum during chronic alcohol intoxication. Bull Exp Biol Med 155:30–33. https://doi.org/10.1007/s10517-013-2072-x
Yakovleva LM, Sorkina OA (2016) Reaction of parotid gland mast cells to chronic alcohol intoxication. Morfologiia 149(2):27–31 [In Russian]
Yu Y, Blokhuis BR, Garssen J, Redegeld FA (2016) Non-IgE mediated mast cell activation. Eur J Pharmacol 778:33–43. https://doi.org/10.1016/j.ejphar.2015.07.017
Zhang T, Finn DF, Barlow JW, Walsh JJ (2016) Mast cell stabilisers. Eur J Pharmacol 778:158–168. https://doi.org/10.1016/j.ejphar.2015.05.071
Author information
Authors and Affiliations
Contributions
All authors substantially contributed to the conception and the design of the work and agreed to be accountable for all aspects of the work. Olga Alexandrovna Sorkina, Marta Igorevna Sergushkina, and Olga Nurzadinovna Solomina carried out the acquisition of data for the work. Olga Alexandrovna Sorkina, Lyubov Mikhailovna Yakovleva, Tatiana Vitalievna Polezhaeva, and Oksana Olegovna Zaitseva analyzed and interpreted the data for the work. Tatiana Vitalievna Polezhaeva, Oksana Olegovna Zaitseva, and Andrey Nikolaevich Khudyakov drafted the article, and all authors revised it for important intellectual content, and read and approved the final article.
Corresponding author
Ethics declarations
Ethical approval
All procedures were carried out in accordance with the Order of the Ministry of Health of the USSR dated 12.08.1977 No. 755 “On measures to further improve organizational forms of work using experimental animals” and with the Federal Law of the Russian Federation “On the protection of animals from cruelty” dated 01.12.1999 No. 4679-II GD. To conduct this study, permission was obtained from the University Ethics Committee (protocol no. 3 of November 16, 2015) in accordance with the order of the USSR Ministry of Health No. 775 of August 12, 1977.
Consent to participate
For this type of study, formal consent is not required.
Consent for publication
For this type of study, formal consent is not required.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sorkina, O., Yakovleva, L., Polezhaeva, T. et al. Morphofunctional state of the salivary glands of Wistar rats under prolonged exposure to alcohol. Comp Clin Pathol 31, 497–507 (2022). https://doi.org/10.1007/s00580-022-03348-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00580-022-03348-y