EFFECT OF STREPTOZOCIN-INDUCED DIABETIC NEUROPATHY ON RAT’S SALIVARY GLANDS

Tykhonovych K. V., Kryvoruchko T. D., Berehovyi S. M., Neporada K. S.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Abstract. During the last decade, there has been a steady increase in the incidence of diabetes (DM) around the world. According to the latest estimates of the International Diabetes Federation, as of 2021, the number of adults with diabetes has reached 537 million. Diabetic neuropathy is the most common complication of diabetes mellitus with high morbidity and mortality and is one of neurodegenerative disorders of the peripheral nervous system. The salivary glands are considered to be the main exocrine glands of the oral cavity and physiologically contribute to the maintenance of oral homeostasis. The literature confirms the correlation between diabetes and salivary gland complications, in particular changes in key proteins in patients with diabetes, which significantly impair salivary gland function.The aim of the study was to investigate the activity of α-amylase, to analyze the proteinase-inhibitory potential, the state of lipid peroxidation, carbonyl oxide stress, antioxidant system in the salivary glands of rats under conditions of streptozocin-induced diabetic neuropathy. Experimental diabetic neuropathy in rats was induced by the intraperitoneal administration of a single injection of sreptozocin at a dose of 65 mg/kg (Streptozocin, “Sigma”, USA). To confirm the presence of diabetes mellitus in rats on the 30th day of the study, a glucose tolerance test was performed. To confirm the development of diabetic neuropathy, we used the strain-algometric method of measuring the pain threshold (Randall-Selitto). In the homogenate of the mandibular salivary glands of rats, we determined α-amylase activity, total proteolytic activity, total antitryptic activity, level of TBA-active products, level of oxidatively modified proteins, level of medium weight molecules and catalase activity. According to our data, streptozocin-induced diabetic neuropathy causes inhibition of the protein-synthetic activity of the mandibular salivary glands of animals, which causes a decrease in amylase activity. Under these conditions, the proteinase-inhibitory balance varies according to the compensatory type. We found that under the conditions of modeling diabetic neuropathy in the tissues of the mandibular salivary glands of rats, lipid peroxidation processes are activated against the background of increased antiradical protection, which indicates a decompensatory balance of pro- and antioxidant systems. Streptozocin-induced diabetic neuropathy promotes the development of pathological changes in the mandibular salivary glands of rats, as evidenced by impaired protein-synthetic function, changes in proteinase-inhibitory and pro / antioxidant balance.

diabetic neuropathy, salivary glands, proteinase-inhibitory potential, pro- and antioxidant systems.

1. International Diabetes Federation. IDF Diabetes Atlas [Internet]. Available from: https://diabetesatlas.org/.
2. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017 Jun;128:40-50. DOI: 10.1016/j.diabres.2017.03.024.
3. Sempere-Bigorra M, Julián-Rochina I, Cauli O. Differences and Similarities in Neuropathy in Type 1 and 2 Diabetes: A Systematic Review. J Pers Med. 2021 Mar 22;11(3):230. DOI: 10.3390/jpm11030230.
4. England JD, Asbury AK. Peripheral neuropathy. Lancet. 2004 Jun 26;363(9427):2151-61. DOI: 10.1016/S0140-6736(04)16508-2.
5. Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019 Jun 13;5(1):41. DOI: 10.1038/s41572-019-0092-1.
6. Juster-Switlyk K, Smith AG. Updates in diabetic peripheral neuropathy. F1000Res. 2016 Apr 25;5:F1000 Faculty Rev-738. DOI: 10.12688/ f1000research.7898.1.
7. Chen SY, Wang Y, Zhang CL, Yang ZM. Decreased basal and stimulated salivary parameters by histopathological lesions and secretory dysfunction of parotid and submandibular glands in rats with type 2 diabetes. Exp Ther Med. 2020 Apr;19(4):2707-2719. DOI: 10.3892/ etm.2020.8505.
8. Sato T, Mito K, Ishii H. Relationship between impaired parasympathetic vasodilation and hyposalivation in parotid glands associated with type 2 diabetes mellitus. Am J Physiol Regul Integr Comp Physiol. 2020 May 1;318(5):R940-R949. DOI: 10.1152/ajpregu.00016.2019.
9. DeVito-Moraes AG, Marques VDD, Caperuto LC, Ibuki FK, Nogueira FN, Francci CE, et al. INitial Steps of Insulin Action in Parotid Glands of Male Wistar Rats. Cell Biochem Biophys. 2021 Aug 3. DOI: 10.1007/s12013-021-01025-5.
10. Kołodziej U, Maciejczyk M, Miąsko A, Matczuk J, Knaś M, Żukowski P, et al. Oxidative Modification in the Salivary Glands of High Fat-Diet Induced Insulin Resistant Rats. Front Physiol. 2017 Jan 26;8:20. DOI: 10.3389/fphys.2017.00020.
11. Velasco-Ortega E, Delgado-Ruiz RA, López-López J. Dentistry and Diabetes: The Influence of Diabetes in Oral Diseases and Dental Treatments. J Diabetes Res. 2016;2016:6073190. DOI:10.1155/2016/6073190.
12. Fouani M, Basset CA, Jurjus AR, Leone LG, Tomasello G, Leone A. Salivary gland proteins alterations in the diabetic milieu. J Mol Histol. 2021 Oct;52(5):893-904. DOI: 10.1007/s10735-021-09999-5.
13. Beregova T, Beregovyi S, Nikitina N, Nozdrenko D, Ostapchenko L. Novel approaches to the treatment of polyneuropathy induced by diabetes type I. 3rd Congress of the European Academy of Neurology, European journal of Neurology. 2017;24(1):228.
14. Randall LO, Selitto JJ. A method for measurement of analgesic activity on inflammed tissue. Arch. Int. Pharmacodyn. Ther. 1957;111:409- 419.
15. Santos-Nogueira E, Redondo Castro E, Mancuso R, Navarro X. Randall-Selitto Test: A New Approach for the Detection of Neuropathic Pain after Spinal Cord Injury. J Neurotrauma. 2012 Mar 20;29(5):898-904. DOI: 10.1089/neu.2010.1700.
16. Caraway WT. A stable starch substrate for the determination of amylase in serum and other body fluids. Am J Clin Pathol. 1959 Jul;32(1):97- 9. DOI: 10.1093/ajcp/32.1_ts.97.
17. Ugolev AM. Issledovanie pishchevaritel’nogo apparata u cheloveka. L.: Nauka; 1969. 216 s. [in Russian].
18. Veremeenko KN. Proteoliz v norme i pri patologii. K.: Zdorov’ya; 1988. 200 s. [in Russian].
19. Stal’naya ID, Garishvili TG. Metod opredeleniya malonovogo dial’degida s pomoshch’yu tiobarbiturovoj kisloty. Sovremennye metody v biokhimii. M.: Medicina; 1977. 392 s. [in Russian].

«Bulletin of problems biology and medicine» Issue 4 (162), 2021 year, 194-198 pages, index UDK 616.833-02:616.379-008.64-02:615.33]:616.316]-092.9

10.29254/2077-4214-2021-4-162-194-198