Comparison the effects of indomethacin, celecoxib and aspirin on sepsis-induced liver injury in the CLP model

Yaghmori, Fariba; Hajihosseini, Reza; Kassaee, Seyed Mehrdad; Seifizarei, Bahram

doi:10.30473/eab.2019.5725

Document Type : Article

Authors

¹ Ph.D., Department of Biology, Hamedan Branch, Islamic Azad University, Hamedan, Iran

² Department of Biology, Payame Noor University, Tehran, Iran

³ Professor of Biochemistry, Biology Department, Faculty of Science, Payame Noor University, Tehran, Iran

⁴ Professor, Department of Biology, Hamedan Branch, Islamic Azad University, Hamedan, Iran

⁵ Researcher, Gastroenterologist and Hepatologist Middle East Liver Disease Center, Hamedan, Iran

https://doi.org/10.30473/eab.2019.5725

Abstract

Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) have beneficial effects in numerous experimental models of sepsis. Therefore, in the present study, we investigated the protective effects of three NSAIDs against sepsis induced liver damages. A total number of 60 male Wistar rats were randomly divided into six experimental groups. Rats were treated with indomethacin, celecoxib and aspirin orally with dose of 2 mg/kg b.w for 48h after CLP (Cecal ligation and puncture) injury. Then, blood samples were collected to determine serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and Bilirubin. The extracted livers were used for biochemical assays [Malondialdehyde (MDA), glutathione (GSH) and myeloperoxidase (MPO) activities] and real time PCR studies. The result revealed that treatments significantly improved antioxidant and liver enzymes by reducing MDA, MPO, AST and ALT level and increasing level of GSH. Moreover, cyclooxygenase-2(COX-2) expression in the liver tissue was decreased in the treatment group compared to the CLP group. Thus, our result suggests CLP induced oxidative hepatic damage and NSAIDs have the potential for the treatment of liver damage consecutive to chemical intoxication.

Keywords

20.1001.1.23222387.1398.7.4.13.2

References

Aydın, S.; Şahin, T.T.; Bacanlı, M.; Taner, G.; Başaran, A.A.; Aydın, M.; Başaran, N.; (2016). Resveratrol protects sepsis-induced oxidative DNA damage in liver and kidney of rats. Balkan Medical Journal; 33(6): 594.

Canabal, J.M.; Kramer, D.J.; (2008). Management of sepsis in patients with liver failure. Curr Opin Crit Care; 14: 189-197.

Cherian, S.; Jameson, S.; Rajarajeswari, C.; Helena, V.; Latha, L.; Anu Rekha, M.R.; Nagamma, T.; Subba Raju, V.; Kini, P.G.; Rao, A.; (2007). Oxidative stress in sepsis in children. Indian J Med Res; 125(2): 143-8.

Dovizio, M.; Tacconelli, S.; Sostres, C.; Ricciotti, E.; Patrignani, P.; (2012). Mechanistic and pharmacological issues of aspirin as an anticancer agent. Pharmaceuticals; 5(12): 1346-1371.

Eliopoulos, A.G.; Dumitru, C.D.; Wang, C.C.; Cho, J.; Tsichlis, P.N.; (2002). Induction of COX‐2 by LPS in macrophages is regulated by Tpl2‐dependent CREB activation signals. The EMBO Journal; 21(18): 4831-4840.

Esmaeili, B.; Rezaee, S.A.R.; Layegh, P.; Tavakkol Afshari, J.; Dye, Ph.; Ghayoor Karimiani, E.; Kalalinia, F.; Rafatpanah, H.; (2011). Expression of IL-17 and COX2 Gene in Peripheral Blood Leukocytes of Vitiligo Patients. Iran J Allergy Asthma Immunol; 10(2): 81-89.

Gustot, T.; Durand, F.; Lebrec, D.; Vincent, J.L.; Moreau, R.; (2009). Severe sepsis in cirrhosis. Hepatology; 50: 2022-2033.

Huang, Y.H.; Tsai, P.S.; Huang, C.J.; (2008). Bupivacaine inhibits COX-2 expression, PGE2, and cytokine production in endotoxin-activated macrophages. Acta Anaesthesiol Scand; 52: 530-535.

Hubbard, W.J.; Choudhry, M.; Schwacha, M.G.; Kerby, J.D.; (2005). Cecal ligation and puncture. Shock; 24(1): 52-57.

Hyder, A.M.; Hasan, M.; Mohieldein, H.A.; (2013). Comparative Levels of ALT, AST, ALP and GGT in Liver associated Diseases. Euro J Exp Bio; 3(2): 280-284.

Juncal, V.R.; Neto, L.A.D.; Camelier, A.A.; Messeder, O.H.C.; Farias, A.M.D.C.; (2011). Clinical impact of sepsis at admission to the ICU of a private hospital in Salvador, Brazil. J Bras Pneumol; 37(1): 85-92.

Kharb S, Singh V, Ghalaut PS, Sharma A, Singh GP. Role of oxygen free radicals in shock. J Assoc Physicians India 2000; 48(10): 956-7.

Kothari, N.; Keshari, R.S.; Bogra, J.; Kohli, M.; Abbas, H.; Malik, A.; et al.; (2011). Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis. J Crit Care; 26(4): 435.e1-7.

Marshall, J.C.; (2012). New translational research provides insights into liver dysfunction in sepsis. PLoS Med; 9: e1001341.

Martin-Loeches, I.; Levy, M.M.; Artigas, A.; (2015). Management of severe sepsis: advances, challenges, and current status. Drug Des Devel Ther; 9: 2079.

Meamarbashi, A.; Rajabi, A.; (2015). Preventive effects of 10-day supplementation with saffron and indomethacin on the delayed-onset muscle soreness. Clin J Sport Med; 25(2): 105-112.

Ortolani, O.; Conti, A.; De Gaudio, A.R.; Moraldi, E.; Cantini, Q.; Novelli, G.; (2000). The effect of glutathione and N-acetylcysteine on lipoperoxidative damage in patients with early septic shock. Am J Respir Crit Care Med; 161(6): 1907.

Prasad, S.; Gupta, S.C.; Tyagi, A.K.; (2017). Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals. Cancer Lett; 387: 95-105.

Rasooli, A.; Fatemi, F.; Hajihosseini, R.; Vaziri, A.; Akbarzadeh, K.; Mohammadi Malayeri, M.R.; Anti-inflammatory and anti-oxidant properties of deuterium depleted water with and without Mentha longifolia essential oils. Pharm Biol. (in Press)

Ricciotti, E.; FitzGerald, G.A.; (2011). Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol.; 31: 986-1000.

Sabina, E.P.; Rasool, M.; Vedi, M.; Navaneethan, D.H.; Ravichander, M.; Parthasarthy, P.; Thella, S.R.; (2013). Hepatoprotective and antioxidant potential of withania somnifera against paracetamol-induced liver damage in rat. Int J Pharm Pharm Sci; 5(2): 648-651.

Seldak, J.; Limdsay.; (1986). Estimation of total protein bound and non-protein sulfidryl groups in tissue with Elman, s reagent. Anal Biochem; 25: 192-205.

Stearns-Kurosawa, D.J.; Osuchowski, M.F.; Valentine, C.; Kurosawa, S.; Remick, D.G.; (2011). The pathogenesis of sepsis. Annu Rev Pathol-Mech; 6: 19-48.

Strong, V.E.M.; Mackrell, P.J.; Concannon, E.M.; Naama, H.A.; Schaefer, P.A.; Shaftan, G.W.; Stapleton, P.P.; Daly, J.M.; (2000). Blocking prostaglandin E2 after trauma attenuates pro-inflammatory cytokines and improves survival. Shock; 14: 374-9.

Tartibian, B.; Derafshi, B.; (2009). The effect of Indomethacin on the biochemical, functional and visual appearance of delayed muscular tachycardia due to eccentric contractions in non-athlete men. J Sports Sci.; 3: 110-93. (in Persian)

Victor, V.M.; Rocha, M.; Fuente, M.D.; (2014). Immune cells: free radicals and antioxidants in sepsis. Int Immunopharmacol; 4: 327-347.

Yan, J.; Li, S.; Li, S.; (2014). The role of the liver in sepsis. Int Rev Immunol; 33: 498-510.

Zhao, H.; Luo, F.; Li, H.; Zhang, L.; Yi, Y.; Wan, J.; (2014). Antinociceptive effect of tetrandrine on LPS-induced hyperalgesia via the inhibition of IKKβ phosphorylation and the COX-2/PGE2 pathway in mice. PLoS One; 9: e94586.

Experimental animal Biology

Comparison the effects of indomethacin, celecoxib and aspirin on sepsis-induced liver injury in the CLP model

References

References

Volume 7, Issue 4 - Serial Number 28
May 2019
Pages 125-134

Comparison the effects of indomethacin, celecoxib and aspirin on sepsis-induced liver injury in the CLP model

References

References

Volume 7, Issue 4 - Serial Number 28May 2019Pages 125-134

Volume 7, Issue 4 - Serial Number 28
May 2019
Pages 125-134