Effect of Anticancer Drugs on Histology of Salivary Glands in Some Laboratory Animals
DOI:
https://doi.org/10.51699/cejsr.v45i3.590Keywords:
histology, anticancer, salivary glands, animals, drugsAbstract
Cancer chemotherapeutic agents are not selective for tumor cells, unfortunately, they damage normal cells. This is based on the type, amount and duration of drug used to treat the cancer. Salivary gland tissues can be affected resulting in morphological and functional changes with an oral manifestation which are especial prominent feature of the toxicity leading mainly to reduction of saliva flow namely xerostomia. The objective was to analyze the effects of anticancer drugs on salivary glands of some animals.
References
[1] C. Paz, A. Glassey, A. Frick, S. Sattar, N. G. Zaorsky, G. C. Blitzer, and R. J. Kimple, “Cancer therapy-related salivary dysfunction,” J. Clin. Invest., vol. 134, no. 17, p. e182661, Sep. 2024, doi: 10.1172/JCI182661.
[2] A. Vistoso Monreal, G. Polonsky, C. Shiboski, V. Sankar, and A. Villa, “Salivary gland dysfunction secondary to cancer treatment,” Front. Oral Health, vol. 3, p. 907778, Jun. 2022, doi: 10.3389/froh.2022.907778.
[3] A. Mahmood, F. Al-Mashhadane, and A. Thanoon, “Effects of dipyridamole on histopathology of salivary glands in rabbits,” Al-Rafidain Dent. J., vol. 24, no. 1, pp. 165–173, 2024, doi: 10.33899/rdenj.2024.145627.1239.
[4] Z. Z. Yurdabakan, I. Ozcan, and S. Solakoğlu, “Effects of chemotherapeutic drugs used in head and neck cancers on submandibular glands of rats,” J. Stomatol., vol. 75, no. 2, pp. 61–71, 2022, doi: 10.5114/jos.2022.117327.
[5] K. Nurgali, R. T. Jagoe, and R. Abalo, “Editorial: Adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae?,” Front. Pharmacol., vol. 9, p. 245, 2018, doi: 10.3389/fphar.2018.00245.
[6] F. Perri, S. Pisconti, and G. D. V. Scarpati, “P53 mutations and cancer: a light linkage,” Ann. Transl. Med., vol. 4, no. 24, p. 522, 2016, doi: 10.21037/atm.2016.12.41.
[7] M. Gackowski, M. Koba, S. Kruszewski, et al., “Pharmacological classification of anticancer drugs applying chromatographic retention data and chemometric analysis,” Chem. Pap., vol. 75, no. 10, pp. 265–278, 2021, doi: 10.1007/s11696-021-01431-w.
[8] P. Zukowski, M. Maciejczyk, J. Matczuk, et al., “Effect of N-acetylcysteine on antioxidant defense, oxidative modification, and salivary gland function in a rat model of insulin resistance,” Oxid. Med. Cell. Longev., vol. 2018, p. 6581970, 2018, doi: 10.1155/2018/6581970.
[9] B. M. Onopiuk, Z. N. Dabrowska, J. Rogalska, et al., “The beneficial impact of black chokeberry extract against oxidative stress in the sublingual salivary gland of rats intoxicated with cadmium,” Oxid. Med. Cell. Longev., vol. 2021, p. 6622245, 2021, doi: 10.1155/2021/6622245.
[10] N. Sardaro, F. Della Vella, M. A. Incalza, et al., “Oxidative stress and oral mucosal diseases: an overview,” In Vivo, vol. 33, pp. 289–296, 2019, doi: 10.21873/invivo.11460.
[11] P. M. Yamaguti, A. Simoes, E. Ganzerla, et al., “Effects of single exposure of sodium fluoride on lipid peroxidation and antioxidant enzymes in salivary glands of rats,” Oxid. Med. Cell. Longev., vol. 2013, p. 674593, 2013, doi: 10.1155/2013/674593.
[12] L. M. P. Fernandes, F. B. Teixeira, S. M. Alves–Junior, et al., “Immunohistochemical changes and atrophy after chronic ethanol intoxication in rat salivary glands,” Histol. Histopathol., vol. 30, pp. 1069–1078, 2015, doi: 10.14670/HH-30.1069.
[13] N. C. F. Fagundes, L. M. P. Fernandes, R. S. O. D. Paraense, et al., “Binge drinking of ethanol during adolescence induces oxidative damage and morphological changes in salivary glands of female rats,” Oxid. Med. Cell. Longev., vol. 2016, p. 7323627, 2016, doi: 10.1155/2016/7323627.
[14] U. Kolodziej, M. Maciejczyk, W. Niklinska, et al., “Chronic high-protein diet induces oxidative stress and alters the salivary gland function in rats,” Arch. Oral Biol., vol. 84, pp. 6–12, 2017, doi: 10.1016/j.archoralbio.2017.09.015.
[15] O. Sorkina, O. Zaitseva, and A. Khudyakov, “The effect of long-term alcohol intoxication on the morphological structures and enzymatic activity of rat salivary glands,” Alcohol, vol. 99, pp. 32–33, 2022, doi: 10.1016/j.alcohol.2021.11.006.
[16] V. R. N. Dos Santos, M. K. M. Ferreira, L. O. Bittencourt, et al., “Maternal fluoride exposure exerts different toxicity patterns in parotid and submandibular glands of offspring rats,” Int. J. Mol. Sci., vol. 23, p. 7217, 2022, doi: 10.3390/ijms23137217.
[17] D. de Souza–Monteiro, P. B. de Oliveira Nunes, R. de Oliveira Ferreira, et al., “Aluminum-induced toxicity in salivary glands of mice after long-term exposure: insights into the redox state and morphological analysis,” Biol. Trace Elem. Res., vol. 198, pp. 575–582, 2020, doi: 10.1007/s12011-020-02116-7
[18] O. Alnuaimi, J. Mammdoh, and L. Al-Allaf, “The role of selenium in mitigating the adverse effect of cyclophosphamide on the rat submandibular salivary glands,” Egypt. J. Vet. Sci., vol. 53, pp. 505–516, 2022, doi: 10.21608/ejvs.2022.126149.1234.
[19] D. Fishbain, “Evidence-based data on pain relief with antidepressants,” Ann. Med., vol. 32, pp. 305–316, 2000, doi: 10.3109/07853890009011775.
[20] N. B. Robinson, K. Krieger, F. M. Khan, et al., “The current state of animal models in research: A review,” Int. J. Surg., vol. 72, pp. 9–13, 2019.
[21] O. A. Mostafa, F. Ibrahim, and E. Boria, “Protective effects of hesperidin in cyclophosphamide-induced parotid toxicity in rats,” Sci. Rep., vol. 13, p. 158, 2023.
[22] W. Y. Abdelzaher, M. A. Nassan, S. M. Ahmed, et al., “Xanthine oxidase inhibitor, febuxostat is effective against 5-fluorouracil-induced parotid salivary gland injury in rats via inhibition of oxidative stress, inflammation, and targeting TRPC1/CHOP signaling pathway,” Pharmaceuticals, vol. 15, p. 232, 2022.
[23] G. d. O. Lopes, W. A. B. Aragão, P. C. Nascimento, et al., “Effects of lead exposure on salivary glands of rats: Insights into the oxidative biochemistry and glandular morphology,” Environ. Sci. Pollut. Res. Int., vol. 28, pp. 10918–10930, 2021.
[24] L. A. do Lima, G. H. N. Miranda, W. A. B. Aragão, et al., “Effects of fluoride on submandibular glands of mice: Changes in oxidative biochemistry, proteomic profile, and genotoxicity,” Front. Pharmacol., vol. 12, p. 715394, 2021.
[25] L. E. Bomfin, C. M. Braga, T. A. Oliveira, et al., “5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition,” Biochem. Pharmacol., vol. 145, pp. 34–45, 2017.
[26] Y. Zhang, N. Yin, S. Liang, et al., “5-Fluorouracil-induced neurotoxicity in rat cerebellum granule cells involves oxidative stress and activation of caspase-3 pathway,” Int. J. Clin. Exp. Med., vol. 12, pp. 2334–2343, 2019.
[27] M. N. Elmansy and E. M. Hegazy, “Evaluation of the apoptotic changes induced by 5-fluorouracil on the lingual mucosa and salivary glands of male albino rats,” Egypt. Dent. J., vol. 66, no. 4, pp. 2354–2362, 2020.
[28] D. B. Longley, D. P. Harkin, and P. G. Johnston, “5-Fluorouracil: Mechanisms of action and clinical strategies,” Nat. Rev. Cancer, vol. 3, pp. 330–338, 2003.
[29] A. Polk, M. Vaage-Nilsen, K. Vistisen, et al., “Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: A systematic review of incidence, manifestations, and predisposing factors,” Cancer Treat. Rev., vol. 39, pp. 974–984, 2013.
[30] A. Ohuchida, A. Furukawa, J. Yoshida, et al., “Micronucleus assays on 5-fluorouracil and 6-mercaptopurine with mouse peripheral blood reticulocytes,” Mutat. Res., vol. 278, pp. 139–143, 1992.
[31] R. M. McQuade, V. Stojanovska, E. Donald, et al., “Gastrointestinal dysfunction and enteric neurotoxicity following treatment with anticancer chemotherapeutic agent 5-fluorouracil,” Neurogastroenterol. Motil., vol. 28, pp. 1861–1875, 2016
[32] C. Pop and G. S. Salvesen, “Human caspases: Activation, specificity, and regulation,” J. Biol. Chem., vol. 284, pp. 21777–21781, 2009.
[33] C. Miquel, F. Borrini, S. Grandjouan, et al., “Role of bax mutations in apoptosis in colorectal cancers with microsatellite instability,” Am. J. Clin. Pathol., vol. 123, pp. 562–570, 2005.
[34] C. Weng, D. Yu, et al., “Specific cleavage of MCl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells,” J. Biol. Chem., vol. 280, pp. 10491–10500, 2015.
[35] D. Westphal, R. M. Kluck, and G. Dewson, “Building blocks of the apoptotic pore: How Bax and Bak are activated and oligomerize during apoptosis,” Cell Death Differ., vol. 21, pp. 196–205, 2014.
[36] D. R. Mellwain, T. Berger, and T. W. Mak, “Caspase functions in cell death and disease,” Cold Spring Harb. Perspect. Biol., vol. 5, p. a008656, 2013.
[37] B. Onopiuk, P. Onopiuk, Z. Dabrowska, et al., “Effect of metronidazole on the oxidoreductive processes in the submandibular and parotid glands in experimental research,” Oxid. Med. Cell. Longev., vol. 2018, p. 7083486, 2018.
[38] A. A. R. Moawad and M. Elhindawy, “The possible protective effect of graviola extract on salivary gland against cytotoxicity during cisplatin treatment (histological, biochemical, and immunohistochemical study),” J. Biol. Chem., vol. 45, no. 2, pp. 588–596, 2022.
[39] A. M. Florea and D. Busselberg, “Cisplatin as an anti-tumor drug: Cellular mechanisms of activity, drug resistance, and induced side effects,” Cancers, vol. 3, no. 1, pp. 1351–1371, 2011.
[40] J. C. Junn, J. J. Sciubba, J. A. Bishop, et al., “The effect of amifostine on submandibular gland histology after radiation,” Int. J. Otolaryngol., p. 508279, 2012.
[41] M. Hanif, et al., “Anticancer metallo drugs: Where is the next cisplatin?,” Future Med. Chem., vol. 2, pp. 941–994, 2018.
[42] S. Dasari, et al., “Cisplatin in cancer therapy: Molecular mechanisms of action,” Eur. J. Pharmacol., vol. 250, p. 58905, 2014.
[43] J. R. Kouvaris, V. E. Kouloulias, and L. J. Valhos, “Amifostine: The first selective-target and broad-spectrum radioprotector,” Oncologist, vol. 12, no. 6, pp. 738–747, 2007.
[44] D. M. Brizel, T. H. Wasserman, M. Henke, et al., “Phase III randomized trial of amifostine as a radioprotector in head and neck cancer,” J. Clin. Oncol., vol. 18, no. 19, pp. 3339–3345, 2000.
[45] V. Rudat, M. Munter, D. Rades, et al., “The effect of amifostine or IMRT to preserve the parotid function after radiotherapy of the head and neck region measured by quantitative salivary gland scintigraphy,” Radiother. Oncol., vol. 89, no. 1, pp. 71–80, 2008.
[46] E. A. Olsen, “The pharmacology of methotrexate,” J. Am. Acad. Dermatol., vol. 35, pp. 306–316, 1991.
[47] British National Formulary, vol. 45, London: BMA RPS, 2003.
[48] F. A. Pickelt and G. T. Terezhalmy, “Cancer chemotherapy,” in Basic Principles of Pharmacology with Dental Hygiene Applications, Lippincott Williams & Wilkins, 2009, p. 282.
[49] E. G. Khedr, S. M. Hany, and A. A. Soliman, “Effect of vitamin C on submandibular salivary gland of methotrexate-treated rats,” Egypt. J. Hosp. Med., vol. 32, pp. 314–324, 2008.
[50] A. D. Al-Moula, M. H. Ahmed, and M. H. Ahmed, “Histological study on the effect of methotrexate on the oral tissues of adult male rabbits,” Al-Rafidain Dent. J., vol. 13, no. 3, pp. 432–441, 2013.
[51] A. Yagiela, F. Dowd, and E. Neidle, “Antineoplastic drugs,” in Pharmacology and Therapeutics for Dentistry, Elsevier Mosby, 5th ed., pp. 697–799, 2004.
[52] D. W. Keys and K. F. Adkins, “Effects of prolonged administration of azathioprine on parotid glands of rats: An assessment by electron microscopy,” Aust. Dent. J., vol. 27, no. 2, pp. 98–102, 1982.
[53] A. Chlarenza, E. Elverdin, and M. Giglio, “Effects of cadmium on the function and structure of the rat salivary glands,” Arch. Oral Biol., vol. 34, no. 12, pp. 999–1002, 1989.
[54] E. Goerttler, H. Kutzner, H. H. Peter, et al., “Methotrexate-induced papular eruption in patients with rheumatic diseases: A distinctive adverse cutaneous reaction produced by methotrexate in patients with collagen vascular diseases,” J. Am. Acad. Dermatol., vol. 40, pp. 702–707, 1999.
[55] A. Wolf, J. E. Moreia, Y. Marmary, and P. C. Fox, “Lack of acute effects of methotrexate on rat parotid salivary gland function,” Arch. Oral Biol., vol. 34, no. 2, pp. 109–115, 1989.
[56] I. Sukhotnik, J. G. Mogilner, R. Karry, et al., “Effects of oral glutamine on enterocyte turnover during methotrexate-induced mucositis in rats,” Digestion, vol. 79, pp. 5–13, 2009.
[57] Y. Muller-Koch, H. Vogelsang, R. Kopp, et al., “HNPCC—Clinical and molecular evidence for a new entity of hereditary colorectal cancer,” Gut, vol. 54, pp. 1676–1678, 2005.
[58] J. M. Kremer, “Toward a better understanding of methotrexate,” Arthritis Rheum., vol. 50, pp. 1370–1382, 2007.
[59] A. J. Al-Nuaimi, E. J. Jabber, M. J. Jawad, M. S. Hassan, A. J. Jihad, and A. K. Al-Shuwaili, “Effects of methotrexate on hepatic and testicular tissues in male rabbits: Histological, hormonal and biochemical analysis,” Iraqi J. Vet. Sci., vol. 37, suppl. I-IV, pp. 211–217, 2023, doi: 10.33899/ijvs.2023.138717.2828.
[60] A. D. Al-Moula, F. A. Al-Mashhadane, and J. K. Mammdoh, “Effects of 6-mercaptopurine on salivary glands in rabbit,” Al-Rafidain Dent. J., vol. 12, no. 2, pp. 266–273, 2012.
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