Fluvoxamine Administration Attenuates Lipopolysaccharide-Induced Pancreatic Damage

Öz

Objective: Certain types of bacteria contain lipopolysaccharide (LPS), which can cause widespread inflammation in the body, including the pancreas. Fluvoxamine (FLV), a selective serotonin reuptake inhibitor (SSRI) commonly prescribed for psychiatric disorders, has been shown to possess anti-inflammatory properties and may be beneficial in conditions involving tissue damage and inflammation. This study aims to evaluate the potential protective effects of FLV against experimentally induced pancreatic disease in rats using LPS. Material and Method: In this experiment, a total of 32 Wistar albino male rats were randomly divided into four groups: control, LPS (5 mg/kg, intraperitoneally (i.p.)), LPS + FLV (50 mg/kg FLV, i.p.) and FLV. The rats were euthanatized 6 hours after the administration of LPS, and serum and pancreas tissue samples were collected during the necropsy for biochemical, histopathological, and immunohistochemical evaluations. Results: According to the study findings, LPS lowered blood glucose levels. Histological examination showed that LPS caused edema, mild infiltration of inflammatory cells, increased vacuolization in the cells of the Langerhans islet, and severe hyperemia. Immunohistochemical investigations revealed a reduction in the expression of insulin and amylin. The biochemical, histopathological, and immunohistochemical outcomes were improved by FLV. Conclusion: The results of this experimental rat model study indicated that LPS causes damage to the endocrine pancreas. However, FLV demonstrated significant ameliorative effects on the pancreas in rats with LPS-induced pancreatitis.

Anahtar Kelimeler

• LPS
• pancreas
• pathology
• biochemistry
• IHC.

Kaynakça

1. 1. Savran M, Ozmen O, Erzurumlu Y, Savas HB, Asci S, Kaynak M. The impact of prophylactic lacosamide on LPS-induced neuroinflammation in aged rats. Inflammation 2019;42(5):1913-1924.
2. 2. Savran M, Aslankoc R, Ozmen O, Erzurumlu Y, Savas HB, Temel EN, et al. Agomelatine could prevent brain and cerebellum injury against LPS-induced neuroinflammation in rats. Cytokine 2020;127:154957.
3. 3. Mohammad S, Thiemermann C. Role of metabolic endotoxemia in systemic inflammation and potential interventions. Front Immunol 2021;11:594150.
4. 4. Asci H, Ozmen O, Erzurumlu Y, Savas HB, Nurlu Temel E, Icten, P, et al. Ameliorative effects of pregabalin on LPS induced endothelial and cardiac toxicity. Biotech Histochem 2021;96(5):364-375.
5. 5. Cankara FN, Kuş MS, Günaydın C, Şafak S, Bilge SS, Ozmen O, et al. The beneficial effect of salubrinal on neuroinflammation and neuronal loss in intranigral LPS-induced hemi-Parkinson disease model in rats. Immunopharmacol Immunotoxicol 2022;44 (2):168-177.
6. 6. Kurt Y, Ozmen O. Protective effect of astaxanthin against LPS-induced oral and nasal mucosal damage. JAMP 2022;4:(4),584-589.
7. 7. Ozmen O, Topsakal S. Preventive effect of agomelatine in lipopolysaccharide-induced pancreatic pathology. Drug Chem Toxicol 2022;45(1):180-184.
8. 8. Topsakal S, Ozmen O, Karakuyu NF, Bedir M, Sancer O. Cannabidiol mitigates LPS-induced pancreatic pathology: A promising therapeutic strategy. Cannabis Cannabinoid Res. 2023 (Online ahead of print). https://doi.org/10.1089/can.2023.0153.

9. 9. Karpińska M, Czauderna M. Pancreas-its functions, disorders, and physiological impact on the mammals' organism. Front Physiol 2022;13:807632.
10. 10. Ozmen O, Sahinduran S, Mor F. Pathological and immunohistochemical examination of the pancreas in subacute endosulfan toxicity in rabbits. Pancreas 2010;39(3):367-370.
11. 11. Irons J. Fluvoxamine in the treatment of anxiety disorders. Neuropsychiatr Dis Treat 2005;1(4):289-299. 12. Sukhatme VP, Reiersen AM, Vayttaden SJ, Sukhatme VV. Fluvoxamine: A review of its mechanism of action and its role in COVID-19. Front Pharmacol 2021;12:652688.
12. 13. Nyirenda JL, Sofroniou M, Toews I, Mikolajewska A, Lehane C, Monsef I. et al. Fluvoxamine for the treatment of COVID-19. Cochrane Database Syst Rev 2022;9(9):CD015391.
13. 14. Vaccaro, MI, Calvo EL, Suburo AM, Sordelli DO, Lanosa G, Iovanna JL. Lipopolysaccharide directly affects pancreatic acinar cells: implications on acute pancreatitis pathophysiology. Dig Dis Sci 2000;45(5):915-926.
14. 15. Cao C, Gao T, Cheng M, Xi F, Zhao C, Yu W. Mild hypothermia ameliorates muscle wasting in septic rats associated with hypothalamic AMPK-induced autophagy and neuropeptides. Biochem Biophys Res Commun 2017;490(3):882-888.
15. 16. Rafiee L, Hajhashemi V, Javanmard SH. Fluvoxamine inhibits some inflammatory gene expression in LPS/stimulated human endothelial cells, U937 macrophages, and carrageenan-induced paw edema in rats. Iran J Basic Med Sci 2016;19(9):977-984.
16. 17. Mazgaeen L, Gurung P. Recent advances in lipopolysaccharide recognition systems. Int J Mol Sci 2020;21(3):379.
17. 18. Stelzer IA, Arck PC. Immunity and the endocrine system. Encyclopedia of Immunobiology 2016;73–85. https://doi.org/10.1016/B978-0-12-374279-7.19001-0
18. 19. Moffa S, Mezza T, Cefalo CMA, Cinti F, Impronta F, Sorice GP, et al., The interplay between the immune system and microbiota in diabetes. Mediators Inflamm 2019;2019:9367404.
19. 20. Topsakal Ş, Ozmen O. İnsan ve hayvanlarda Diabetes mellitus. MAKU Vet Fak Derg 2016;1(1):47-57.
20. 21. Wernly B, Lichtenauer M, Hoppe UC, Jung C. Hyperglycemia in septic patients: An essential stress survival response in all, a robust marker for risk stratification in some, to be messed with in none. J Thorac Dis 2016;8(7):E621–E624.
21. 22. Stevens JR, McMillan RP, Resendes JT, Lloyd SK, Ali MM, Frisard MI, et al. Acute low-dose endotoxin treatment results in improved whole-body glucose homeostasis in mice. Metabolism 2017;68:150–162.
22. 23. Schmitz O, Brock B, Rungby J. Amylin agonists: A novel approach in the treatment of diabetes. Diabetes 2004;53:Suppl3,S233–S238.
23. 24. Kiriyama Y, Nochi H. Role and cytotoxicity of amylin and protection of pancreatic islet β-cells from amylin cytotoxicity. Cells 2018;7(8):95.
24. 25. Müller TD, Finan B, Clemmensen C, DiMarchi RD, Tschöp MH. The new biology and pharmacology of glucagon. Physiological Reviews 2017;97(2):721-766.
25. 26. Ozmen O, Topsakal S. Pregabalin ameliorates lipopolysaccharide-induced pancreatic inflammation in aged rats. Endocrine, Metabolic & Immune Disorders - Drug Targets 2019:19(8):1141-1147.