Research Article
BibTex RIS Cite

Investigation of the changes in hepatic 5-hydroxytryptamine 2A receptor levels caused by lipopolysaccharide of Porphyromonas gingivalis and the effect of Thymoquinone on these changes.

Year 2025, Volume: 10 Issue: 2, 108 - 114, 31.08.2025
https://doi.org/10.31797/vetbio.1655445

Abstract

Background: The present study aimed to assess the effect of Porphyromonas gingivalis-Lipopolysaccharide (P.gingivalis-LPS) on hepatic disorder mediated by 5-hydroxytryptamine receptor 2A (HT2AR) and whether there is any impact of Thymoquinone (TQ) administration. Methods: 10 µl P. gingivalis-LPS (1mg/ml) injected 6 times at 48-hour intervals into the palatal gingiva of rats. TQ was given by oral gavage (10 mg/kg per day) for two weeks. HT2AR and pro-caspase-3 levels were measured by the enzyme-linked immunosorbent assay (ELISA). Morphological changes in the liver were identified by hematoxylin and eosin staining. Results: In the P.gingivalis-LPS injected group, the hepatic HT2AR levels increased while pro-caspase-3 levels decreased, disturbing the liver morphological structure. TQ administration increased pro-caspase-3 levels and improved morphological structure despite increased HT2AR levels. Conclusion: Our results suggest that oral application of P. gingivalis-LPS decreased pro-caspase 3, an inactive form of caspase-3 by HT2AR, probably due to increased cleaved caspase-3 levels, and TQ administration increased pro-caspase-3 levels, leading to improved liver morphological structure. Therephore, our study indicated that oral pathogen P. gingivalis might impact the liver HT2AR-mediated, and TQ may have a beneficial effect.

Ethical Statement

30.01.2025-2025/2-9

References

  • Afsar, E., & Kantar, D. (2025). How does zinc chelation affect liver sphingolipid metabolism in an Alzheimer's-like model? J Trace Elem Med Biol, 87, 127589. https://doi.org/10.1016/j.jtemb.2025.127589
  • Albuquerque-Souza, E., & Sahingur, S. E. (2022). Periodontitis, chronic liver diseases, and the emerging oral-gut-liver axis. Periodontol 2000, 89(1), 125-141. https://doi.org/10.1111/prd.12427
  • Ali, M. Y., Akter, Z., Mei, Z., Zheng, M., Tania, M., & Khan, M. A. (2021). Thymoquinone in autoimmune diseases: Therapeutic potential and molecular mechanisms. Biomedicine & Pharmacotherapy, 134, 111157. https://doi.org/10.1016/j.biopha.2020.111157
  • Ates, M. B., Ortatatli, M., Oguz, H., Ozdemir, O., Terzi, F., Ciftci, M. K., & Hatipoglu, F. (2022). The ameliorative effects of Nigella sativa, thymoquinone, and bentonite against aflatoxicosis in broilers via AFAR and Nrf2 signalling pathways, and down-regulation of caspase-3. Br Poult Sci, 63(3), 332-339. https://doi.org/10.1080/00071668.2021.1998366
  • Atteya, M., Ahmed, A. M., AlRabiah, A., Al-Matrafi, T. A., Arafah, M. M., Al-Saggaf, S., Shereef, S. H., Ahmed, A. A. H., Alqahtani, H. M., & Mohammad, R. A. T. (2019). Thymoquinone and curcumin modify inducible nitric oxide synthase, caspase 3, and thioredoxin immunohistochemical expression in acetaminophen hepatotoxicity. Folia Morphol (Warsz), 78(4), 773-788. https://doi.org/10.5603/FM.a2019.0027
  • Bajaj, J. S., Betrapally, N. S., Hylemon, P. B., Heuman, D. M., Daita, K., White, M. B., Unser, A., Thacker, L. R., Sanyal, A. J., Kang, D. J., Sikaroodi, M., & Gillevet, P. M. (2015). Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy. Hepatology, 62(4), 1260-1271. https://doi.org/10.1002/hep.27819
  • Beaudry, P., Hadengue, A., Callebert, J., Gaudin, C., Soliman, H., Moreau, R., Launay, J. M., & Lebrec, D. (1994). Blood and plasma 5-hydroxytryptamine levels in patients with cirrhosis. Hepatology, 20(4 Pt 1), 800-803. https://doi.org/10.1002/hep.1840200405
  • Bhattarai, G., Poudel, S. B., Kook, S. H., & Lee, J. C. (2016). Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis. Acta Biomaterialia, 29, 398-408. https://doi.org/10.1016/j.actbio.2015.10.031
  • Breard, M., & Grillon, C. (2009). Serotonin binds to purified neuronal nitric oxide synthase: a possible explanation for ROS production induced by 5HT in the presence of nNOS. Free Radic Res, 43(3), 206-213. https://doi.org/10.1080/10715760802676662
  • Bui, F. Q., Almeida-da-Silva, C. L. C., Huynh, B., Trinh, A., Liu, J., Woodward, J., Asadi, H., & Ojcius, D. M. (2019). Association between periodontal pathogens and systemic disease. Biomedical Journal, 42(1), 27-35. https://doi.org/10.1016/j.bj.2018.12.001
  • Dera, A. A., Rajagopalan, P., Alfhili, M. A., Ahmed, I., & Chandramoorthy, H. C. (2020). Thymoquinone attenuates oxidative stress of kidney mitochondria and exerts nephroprotective effects in oxonic acid-induced hyperuricemia rats. Biofactors, 46(2), 292-300. https://doi.org/10.1002/biof.1590
  • Ebrahimkhani, M. R., Oakley, F., Murphy, L. B., Mann, J., Moles, A., Perugorria, M. J., Ellis, E., Lakey, A. F., Burt, A. D., Douglass, A., Wright, M. C., White, S. A., Jaffre, F., Maroteaux, L., & Mann, D. A. (2011). Stimulating healthy tissue regeneration by targeting the 5-HT(2)B receptor in chronic liver disease. Nat Med, 17(12), 1668-1673. https://doi.org/10.1038/nm.2490
  • Eskandari, E., & Eaves, C. J. (2022). Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis. Journal of Cell Biology, 221(6). https://doi.org/10.1083/jcb.202201159
  • Fu, J. H., Ma, S. X., Li, X., An, S. S., Li, T., Guo, K. K., Lin, M., Qu, W., Wang, S. S., Dong, X. Y., Han, X. Y., Fu, T., Huang, X. P., Wang, T. Y., & He, S. Y. (2016). Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver. International Journal of Biological Sciences, 12(2), 219-234. https://doi.org/10.7150/ijbs.13062
  • Hao, T., Zhang, R., Zhao, T., Wu, J., Leung, W. K., Yang, J., & Sun, W. B. (2023). infection promotes inflammation via inhibition of the AhR signalling pathway in periodontitis. Cell Proliferation, 56(2). https://doi.org/10.1111/cpr.13364
  • Kim, D. C., Jun, D. W., Kwon, Y. I., Lee, K. N., Lee, H. L., Lee, O. Y., Yoon, B. C., Choi, H. S., & Kim, E. K. (2013). 5-HT2A receptor antagonists inhibit hepatic stellate cell activation and facilitate apoptosis. Liver Int, 33(4), 535-543. https://doi.org/10.1111/liv.12110
  • Leira, Y., Iglesias-Rey, R., Gómez-Lado, N., Aguiar, P., Campos, F., D'Aiuto, F., Castillo, J., Blanco, J., & Sobrino, T. (2019). lipopolysaccharide-induced periodontitis and serum amyloid-beta peptides. Archives of Oral Biology, 99, 120-125. https://doi.org/10.1016/j.archoralbio.2019.01.008
  • Lesurtel, M., Soll, C., Humar, B., & Clavien, P. A. (2012). Serotonin: a double-edged sword for the liver? Surgeon, 10(2), 107-113. https://doi.org/10.1016/j.surge.2011.11.002
  • Li, H. Y., Huang, S. Y., Zhou, D. D., Xiong, R. G., Luo, M., Saimaiti, A., Han, M. K., Gan, R. Y., Zhu, H. L., & Li, H. B. (2023). Theabrownin inhibits obesity and non-alcoholic fatty liver disease in mice via serotonin-related signaling pathways and gut-liver axis. Journal of Advanced Research, 52, 59-72. https://doi.org/10.1016/j.jare.2023.01.008
  • Liang, C., Chen, W., Zhi, X., Ma, T., Xia, X. F., Liu, H., Zhang, Q., Hu, Q. D., Zhang, Y., Bai, X. L., & Liang, T. B. (2013). Serotonin promotes the proliferation of serum-deprived hepatocellular carcinoma cells via upregulation of FOXO3a. Molecular Cancer, 12. https://doi.org/Artn 14 10.1186/1476-4598-12-14
  • Lontchi-Yimagou, E., Sobngwi, E., Matsha, T. E., & Kengne, A. P. (2013). Diabetes mellitus and inflammation. Curr Diab Rep, 13(3), 435-444. https://doi.org/10.1007/s11892-013-0375-y
  • Lu, X. Y., Xuan, W. T., Li, J. J., Yao, H. W., Huang, C., & Li, J. (2021). AMPK protects against alcohol-induced liver injury through UQCRC2 to up-regulate mitophagy. Autophagy, 17(11), 3622-3643. https://doi.org/10.1080/15548627.2021.1886829
  • Lu, Z. Y., Li, Y. C., Chowdhury, N., Yu, H., Syn, W. K., Lopes-Virella, M., Yilmaz, Ö., & Huang, Y. (2023). The Presence of Periodontitis Exacerbates Non-Alcoholic Fatty Liver Disease via Sphingolipid Metabolism-Associated Insulin Resistance and Hepatic Inflammation in Mice with Metabolic Syndrome. International Journal of Molecular Sciences, 24(9). https://doi.org/ARTN 832210.3390/ijms24098322
  • Nonogaki, K. (2022). The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases. Int J Mol Sci, 23(3). https://doi.org/10.3390/ijms23031600
  • Ozdemir, H., Kara, M. I., Erciyas, K., Ozer, H., & Ay, S. (2012). Preventive effects of thymoquinone in a rat periodontitis model: a morphometric and histopathological study. Journal of Periodontal Research, 47(1), 74-80. https://doi.org/10.1111/j.1600-0765.2011.01406.x
  • Pagire, H. S., Pagire, S. H., Jeong, B. K., Choi, W. I., Oh, C. J., Lim, C. W., Kim, M., Yoon, J., Kim, S. S., Bae, M. A., Jeon, J. H., Song, S. M., Lee, H. J., Lee, E. Y., Goughnour, P. C., Kim, D., Lee, I. K., Loomba, R., Kim, H., & Ahn, J. H. (2024). Discovery of a peripheral 5HT antagonist as a clinical candidate for metabolic dysfunction-associated steatohepatitis. Nature Communications, 15(1). https://doi.org/ARTN 64510.1038/s41467-024-44874-3
  • Rincic, G., Gacina, P., Jukic, L. V., Rincic, N., Bozic, D., & Badovinac, A. (2021). Association between Periodontitis and Liver Disease. Acta Clinica Croatica, 60(3), 510-518. https://doi.org/10.20471/acc.2021.60.03.22
  • Ruddell, R. G., Oakley, F., Hussain, Z., Yeung, I., Bryan-Lluka, L. J., Ramm, G. A., & Mann, D. A. (2006). A role for serotonin (5-HT) in hepatic stellate cell function and liver fibrosis. American Journal of Pathology, 169(3), 861-876. https://doi.org/10.2353/ajpath.2006.050767
  • Vernerova, A., Krcmova, L. K., Heneberk, O., Radochova, V., & Svec, F. (2022). Liquid chromatography method with tandem mass spectrometry and fluorescence detection for determination of inflammatory biomarkers in gingival crevicular fluid as a tool for diagnosis of periodontal disease. J Pharm Biomed Anal, 212, 114644. https://doi.org/10.1016/j.jpba.2022.114644
  • Zenobia, C., & Darveau, R. P. (2022). Does Oral Endotoxin Contribute to Systemic Inflammation? Frontiers in Oral Health, 3. https://doi.org/ARTN 911420 10.3389/froh.2022.911420
There are 30 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other), Veterinary Biochemistry
Journal Section Research Articles
Authors

Ebru Afşar 0000-0002-7817-855X

Işıl Eranıl 0000-0001-9557-8523

Erkan Özkan 0000-0002-5251-2302

Erdem Aslan 0000-0002-4992-5915

Kadirhan Doğan 0000-0002-0249-1435

Mehmet Öz 0000-0003-4167-2623

Publication Date August 31, 2025
Submission Date March 11, 2025
Acceptance Date June 30, 2025
Published in Issue Year 2025 Volume: 10 Issue: 2

Cite

APA Afşar, E., Eranıl, I., Özkan, E., … Aslan, E. (2025). Investigation of the changes in hepatic 5-hydroxytryptamine 2A receptor levels caused by lipopolysaccharide of Porphyromonas gingivalis and the effect of Thymoquinone on these changes. Journal of Advances in VetBio Science and Techniques, 10(2), 108-114. https://doi.org/10.31797/vetbio.1655445

22563   CABI-Logo_NEW_accessible.jpg   logo_world_of_journals_no_margin.png  download download   download   download        download