Induced arthritis, hepatocytes cytotoxicity and non-steroidal anti-inflammatory drugs (NSAIDs) – experimental study

Authors

DOI:

https://doi.org/10.33448/rsd-v11i10.33047

Keywords:

Meloxicam; Zymosan; Induced arthritis.

Abstract

This study aimed to histologically evaluate the pharmacological activity of meloxicam, COX-2 inhibitor, on liver function in arthritic rats. Meloxicam is a non-steroidal anti-inflammatory drug (NSAID), COX-2 inhibitor, generally prescribed in the area of rheumatology. Thus, 18 Wistar rats were divided into 3 groups with 6 animals each: G1 (Negative Control), G2 (Arthritis induced with Zymosan [Zy]), G3 (Arthritis induced with Zymosan [Zy] and treated with meloxicam). The G3 treatment started on the 21st day after induction. The animals were sacrificed, by overdose of Ketamine/Xylazine, seven, 14 and 21 days after the beginning of the meloxicam treatment. Liver samples were collected from the animals, fixed in Millonig buffer containing 10% formaldehyde and processed for conventional histological analysis. G1 animals showed absence of inflammation and degeneration of hepatocytes. In the G2 group, a slight cytoplasmic alteration was observed at seven and 14 days. At 21 days, intense cytoplasmic and nuclear disorganization was detected, accompanied by cell necrosis. In G3, large spacing between sinusoid capillaries was detected. In some 14-day-old animals, amyloidosis was observed, with the presence of a large number of vacuolated hepatocytes involved in an amorphous mass of necrotic cells. Most of the hepatocyte nuclei had compacted chromatin, evidencing cellular degeneration. Meloxican, used as an anti-inflammatory in the synovial region, showed that, in addition to its beneficial effects for the treatment of rheumatological diseases, it is capable of, when administered orally, promoting a high level of liver damage.

References

Bhat, M. A., Al-Omar, M. A., Raish, M., Ansari, M. A., Abuelizz, H. A., Bakheit, A. H., & Naglah, A. M. (2018). Indole derivatives as cyclooxygenase inhibitors: synthesis, biological evaluation and docking studies. Molecules, 23(6), 1250.

Bindu, S., Mazumder, S., & Bandyopadhyay, U. (2020). Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochemical pharmacology, 180, 114147. https://doi.org/10.1016/j.bcp.2020.114147

Bogdanske, J. J., Hubbard-Van Stelle, S., Riley, M. R., & Schiffman, B. (2010). Laboratory mouse procedural techniques: manual and DVD. CRC Press.

Camplesi, A. C. (2010). Uso de antiinflamatórios COX-2 seletivos em ratos (Rattus novergicus) Wistar.

Cheville, N.F. (1994). Ultrastructural pathology: An introduction to interpretation. Ames, IA: Iowa State University Press;

Derbocio, A. M. (2005). The hemodynamic effects of zymosan in the perfused rat liver. Vascular Pharmacology; 43:75-85.

Furst, D. E. (1997). Meloxicam: Selective COX-2 inhibition in clinical practice, Seminars in Arthritis and Rheumatism, 26, Suppl1:21-27.

Ju, Z., Li, M., Xu, J., Howell, D. C., Li, Z., & Chen, F. E. (2022). Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years. Acta Pharmaceutica Sinica B. 12(6): 2790–2807.

Guicciardi, M. E., & Gores, G. J. (2005). Apoptosis: a mechanism of acute and chronic liver injury. Gut, 54(7), 1024–1033.

Khalil, N. Y., & Aldosari, K. F. (2020). Chapter Six - Meloxicam, Editor(s): Harry G. Brittain, Profiles of Drug Substances, Excipients and Related Methodology, Academic Press, 45,2020, 159-197.

Kummer, C. L., & Coelho T. C. R. B. (2002). Antiinflamatórios Não Esteróides Inibidores da Ciclooxigenase-2 (COX-2): Aspectos Atuais. Rev Bras Anestesiol. 52: 4: 498-512.

Lida, V. H. (2005) Cirrose Hepática: Aspectos morfológicos relacionados as suas possíveis complicações. Um estudo centrado em necropsias. J Bras patol Med lab. 41:1, 29-36.

Maddrey, W. C., Maurath, C. J., & Verburg K. M. (2000). The hepatic safety and tolerability of the novel cyclooxygenase inhibitor celecoxib. Am J Ther. 7:153-158.

Manov, I., Motanis, H., Frumin, I., & Iancu, T. C. (2006) Acta Pharmacologica Sinica; 27 (3): 259–272

Meunier, L., & Larrey, D. (2018). Recent Advances in Hepatotoxicity of Non-Steroidal Anti-inflammatory Drugs, Annals of Hepatology, 17, Issue 2,187-191.

Morsoleto, M. J. M. S. (2007) Clinical and morphological evolution of the induced experimental arthritis in Rattus novergicus albinus Braz. J. Morphol. Sci; 24 (2): 75-81.

Morsoleto, F. M. S., Werneck, P. R., Bomfim, F. R. C., Esquisatto, M. A. M., & Morsoleto, M. J. M. (2022). Therapeutic ultrasound and essential oil of melaleuca alternifolia interfere with muscle regeneration?. Research, Society and Development, 11(6), e10411628791. https://doi.org/10.33448/rsd-v11i6.28791

Morsoleto, F. M. S., Werneck, P. R., Bomfim, F. R. C., & Morsoleto, M. J. M. S. (2022). Ultrasound wave transports apitoxin in arthritic joint. - Experimental study. Research, Society and Development, 11(7).

O´Beirne, J. P., & Cairns, S. R. (2000) Cholestatic hepatitis in association with celecoxib. Br Med J, 323:23.

Parolin, M. B., & Reason, I. J. M. (2001). Apoptose como mecanismo de lesão nas doenças hepatobiliares. Arquivos de Gastroenterologia, 38, 138-144.

Pedroso, C. R., Batista, L. F. (2017). O uso indiscriminado dos antiinflamatórios não esteroidais. Saúde & Ciência Em Ação. 3: 01:48-69.

Porta, G. Autoimmune hepatitis. Jornal de Pediatria 2000; Sociedade Brasileira de Pediatria 76 (2): 181-186.

Samra, M. M., Sadia, A., Azam, M., Imran, M., Ahmad, I., & Basra, M. A. R. (2022). Synthesis, Spectroscopic and Biological Investigation of a New Ca (II) Complex of Meloxicam as Potential COX-2 Inhibitor. Arabian Journal for Science and Engineering, 1-18.

Sriuttha, P., Sirichanchuen, B., & Permsuwan, U. (2018). Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials. International journal of hepatology, 5253623. https://doi.org/10.1155/2018/5253623

Sylvester, J. (2019). Anti-inflamatórios não-esteroides. Sociedade Brasileira de Anestesiologia ATOTW ,405, 1-5.

Vane, J. R. (1996). Introduction: mechanism of action of NSAIDS. British Journal of Rheumatol, 35 (1): 1-3.

Willoughby, D. A., Moore, A. R., & Colville-Nash, P. R. (2000). COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease. The Lancet, 355(9204), 646-648.

Downloads

Published

09/08/2022

How to Cite

MORSOLETO, F. M. da S. .; WERNECK, P. R. .; MOREIRA, J. A. R. .; BOMFIM, F. R. C. do .; ESQUISATTO, M. A. M. .; MORSOLETO, M. J. M. da S. . Induced arthritis, hepatocytes cytotoxicity and non-steroidal anti-inflammatory drugs (NSAIDs) – experimental study. Research, Society and Development, [S. l.], v. 11, n. 10, p. e526111033047, 2022. DOI: 10.33448/rsd-v11i10.33047. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/33047. Acesso em: 4 oct. 2022.

Issue

Section

Health Sciences