Therapeutic Efficacy of Ursodeoxycholic Acid (Fortibile® tablet) on Nonsteroidal Anti-Inflammatory Drug (NSAID)-induced Hepatic Dysfunction in Experimental Animals
Ameliorative effects of Fortibile® tablet on NSAID-induced hepatic dysfunction
Background: Hepatotoxicity is one of the common side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Scientific study stated that hepatotoxicity is the most serious adverse effects of Aceclofenac.
Objectives: In this study, our aim was to investigate the use of Fortibile® tablet containing ursodeoxycholic acid (UDCA) in prevention of the hepatotoxic effect and biochemical changes induced by aceclofenac (ACE) in laboratory mice.
Materials and Methods: Swiss albino mice were divided into four groups (control, UDCA (Fortibile® tablet) 20 mg/kg, aceclofenac (ACE) 50mg/kg, UDCA 20 mg/kg + aceclofenac 50 mg/kg).
Results: Administration of aceclofenac (ACE) showed decline body weight, food consumption, water intake and elevated liver weight in mice whereas treatment with UDCA (Fortibile® tablet) normalized the same as compared with untreated animals. Animals treated with aceclofenac caused elevated activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) as well as total and direct bilirubin level. These elevations in liver enzymes were decreased by combination of aceclofenac with UDCA. On the other hand application of aceclofenac (ACE) on mice caused a significant increase in serum and tissue malondialdehyde (MDA) and nitric oxide (NO) content but significant decrease in glutathione GSH and GPx content. Combine thepary of UDCA and aceclofenac resulted in a significant decrease in MDA, NO content and significantly elevated GSH and GPx content.
Conclusion: It could be concluded that Fortibile® tablet containing Ursodeoxycholic acid acts as an effective hepatoprotective agent against NSAIDs induced liver dysfunction, and this effect might be related to its antioxidant properties. Hepatic functions should be monitored, and the dose should be adjusted during aceclofenac (ACE) therapy.
Keywords: Ursodeoxycholic acid, Aceclofenac, Hepatotoxicity, Liver function test, Oxidative stress,
2. Spangenberg HC. Drug induced liver injury, Deutsche Medizinische Wochenschri, 2016; 141(23):1688–1691.
3. Karimi-Khouzani O, Heidarian E, Amini SA. Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats. Pharmacol Rep, 2017; 69(4):830–835.
4. Darbar S, Bose A, Bhaumik U, Chatterjee N, Roy Bikash, Chattaraj T K, Das A, Pal T K . Antioxidant and Hepatoprotective Effect of Azadirachta indica leaf Extract on Aceclofenac induced Hepatotoxicity in Rats. Journal of Pharmaceutical Research, 2009; 8(2):116-121.
5. Esmaeilzadeh M, Heidarian E, Shaghaghi M, Roshanmehr H, Najafi M, Moradi A, Nouri A. Gallic acid mitigates diclofenac-induced liver toxicity by modulating oxidative stress and suppressing IL-1b gene expression in male rats. Pharmaceutical Biology, 2020; 58(1):590-596.
6. Buryova H, Chalupsky K, Zbodakova O, Kanchev I, Jirouskova M, Gregor M, Sedlacek R. Liver protective effect of ursodeoxycholic acid includes regulation of ADAM17 activity. BMC Gastroenterology, 2013; 13:1-13
7. Poupon RE: Ursodeoxycholic acid for primary biliary cirrhosis: lessons from the past–issues for the future. J Hepatol, 2000; 32(4):685–688.
8. Stine J, Lewis J. Hepatotoxicity of antibiotics: a review and update for the clinician. Clin Liver Dis, 2013; 17:606–642.
9. Raghunath M, Bakal S. Formulation and evaluation of a fixed dose combination of ceftriaxone disodium and ornidazole. Int J Pharm Life Sci, 2013; 5:750–756.
10. Elsayed M, Elkomy A, Aboubakr H. Effect of ceftriaxone on isolated gastrointestinal, tracheal and uterine smooth muscles. Int J Pharm Sci Res, 2011; 2:2347–2351.
11. Simmons C. From Your Newsletter Beware: Antibiotic-induced hepatotoxicity is rare but deadly. Hosp Pharm, 2002; 37:326–333.
12. Vial T, Biour M, Descotes J, Trepo C. Antibiotic-associated hepatitis: update from 1990. Ann Pharmacother, 1997; 31:204–220.
13. Bell M, Stockwell D, Luban N, Shirey R, Shaak L, Ness P, Wong E. Ceftriaxone-induced hemolytic anemia and hepatitis in an adolescent with hemoglobin SC disease. Pediatr Crit Care Med, 2005; 6:363–366.
14. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol, 1957; 28:56–63.
15. Belfield A, Goldberg D. Revised assay for serum phenyl phosphatase activity using 4-amino-antipyrine. Enzyme, 1971; 12:561–573.
16. Walters M, Gerarde H. An ultramicromethod for the determination of conjugated and total bilirubin in serum or plasma. Microchem J, 1970; 15:231–243.
17. Ohkawa H. Assay for lipid peroxide in animal tissue by thiobarbituric acid reaction. Anal Biochem, 1979; 95:351–358.
18. Miranda K, Espey M, Wink D. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide, 2001; 5:62–71.
19. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys, 1959; 82(1):70–77.
20. Hafeman D, Sunde R, Hoekstra W. Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J Nutre, 1974; 4(5):580–587.
21. Nnodim J, Emejulu A, Amaechi A, NwosuNjoku E. Alterations in biochemical parameters of Wistar rats administered with sulfadoxine and pyrimethamine (Fansidar). Al Ameen J Med Sci, 2010; 3:317–21.
22. Khaled A. Alhumaidha, Sally A. El-Awdan, Wafaa I. El-Iraky, Ezz-El-Din S. El-Denshary. Protective effects of ursodeoxycholic acid on ceftriaxone-induced hepatic injury. Bulletin of Faculty of Pharmacy, Cairo University, 2014; 52 45–50.
23. Gaw A, Cowan R, O’Reilly D, Stewart M, Shepherd J. Clinical biochemistry an illustrated color text. 1st ed. New York: Churchill Livingstone; 1999, p. 51–3.
24. Sario AD, Candelaresi C, Omenetti A, Benedetti A. Vitamin E in chronic liver diseases and liver fibrosis. Vitam Horm, 2007; 76:551–573.
25. Mitsuyoshi H, Nakashima T, Sumida Y, Yoh T, Nakajima Y, Ishikawa H, Kashima K, et al. Ursodeoxycholic acid protects hepatocytes against oxidative injury via induction of antioxidants. Biochem Biophys Res Commun, 1999; 263:537–542.
26. Okada K, Shoda J, Taguchi K, Maher J, Ishizaki K, Inoue Y, Yamamoto M, et al. Ursodeoxycholic acid stimulates Nrf2-mediated hepatocellular transport, detoxification, and antioxidative stress systems in mice. Am J Physiol Gastr L, 2008; 295:735–747.
27. Mohammed M, Farid S, Khaleel S, Sabry N, El-Sayed M. Hepatoprotective efficacy of ursodeoxycholic acid in pediatrics’ acute lymphoblastic leukemia. Pediatr Hematol Oncol, 2012; 29:627–632.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).