Role of Cryopreserved Placenta Extract in Prevention and Treatment of Paracetamol-Induced Hepatotoxicity in Rats
Abstract
Background/Aim: Drug-induced liver injury is one of the major causes of acute liver failure. Under current circumstances of the pandemic of COVID-19 pandemic, the use of paracetamol which has a proven hepatotoxic effect has increased. This prompts the search for novel agents with hepatoprotective properties. The purpose of this article was to evaluate the hepatoprotective activity of cryoextract of the placenta (CEP) on the model of paracetamol-induced hepatitis.
Methods: The study was performed on 28 male rats. Acute drug liver damage was modelled by intragastric administration of paracetamol twice at a dose of 1250 mg/kg.
Results: The development of paracetamol-induced hepatitis in rats was accompanied by a 71.3 % increase (p < 0.001) in the content of active products of thiobarbituric acid (TBA-AP) in liver homogenates as compared with intact animals. Besides, there was a 2.1-fold (p < 0.001) increase of ALT activity, a 58.8 % increase (p < 0.001) of AST activity and a 4.2-fold (p < 0.001) increase of the concentration of total bilirubin as compared with intact rats. The use of cryopreserved placenta extract showed significant hepatoprotection in a rat model of paracetamol-induced hepatitis. This was demonstrated by a 2.3-fold (p < 0.01) increase of the antioxidant-prooxidant index, a significant (p < 0.001) decrease of activity of ALT (by 44.0 %) and AST (by 29.6 %), as well as by a decrease of direct bilirubin level by 52.5 % (p < 0.001) in animals treated with CEP as compared with rats without treatment.
Conclusion: The development of acute paracetamol-induced hepatitis in rats was associated with activation of lipid peroxidation processes in liver tissues, while CEP showed marked hepatoprotective activity in paracetamol-induced hepatitis in rats.
References
1. Andrade RJ, Chalasani N, Bjornsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, et al. Drug-induced liver injury. Nat Rev Dis Primers 2019;5:58. doi: 10.1038/s41572-019-0105-0.
2. Garcia-Cortes M, Robles-Diaz M, Stephens C, Ortega-Alonso A, Lucena MI, Andrade RJ. Drug induced liver injury: an update. Arch Toxicol 2020;94:3381–407.
3. Alempijevic T, Zec S, Milosavljevic T. Drug-induced liver injury: Do we know everything? World J Hepatol 2017;9:491–502.
4. Reuben A, Koch DG, Lee WM, Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010;52:2065–76.
5. Chalasani NP, Hayashi PH, Bonkovsky HL. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 2014;109:950–66.
6. McAtee C. Drug-Induced Liver Injury. Crit Care Nurs Clin North Am 2022;34:267–75.
7. Yimin M. HepaTox: The professional networking platform for promoting clinical and translational research of drug-induced liver injury in China. Chin Hepatol 2014;8:575–6.
8. Licata A. Adverse drug reactions and organ damage: the liver. Eur J Intern Med 2016;28:9–16.
9. Bjornsson HK, Bjornsson ES. Drug-induced liver injury: pathogenesis, epidemiology, clinical features, and practical management. Eur J Intern Med 2022;97:26-31.
10. Kumachev A, Wu PE. Drug-induced liver injury. CMAJ 2021 Mar 1;193(9):E310. doi: 10.1503/cmaj.202026.
11. Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2008;14:6774–85.
12. Jaeschke H, Akakpo JY, Umbaugh DS, Ramachandran A. Novel therapeutic approaches against acetaminophen-induced liver injury and acute liver failure. Toxicol Sci 2020;174:159–67.
13. Chao X, Wang H, Jaeschke H, Ding WX. Role and mechanisms of autophagy in acetaminophen-induced liver injury. Liver Int 2018;38:1363–74.
14. Hladkykh FV, Chyzh MO, Manchenko AO, Belochkіna IV, Mikhailova IP. Effect of cryopreserved placenta extract on some biochemical indices of therapeutic efficiency and toxicity of diclofenac sodium in adjuvant-induced experimental arthritis. Pharm Pharmacol 2021;9:278–93.
15. Hladkykh FV. The effect of meloxicam and cryopreserved placenta extract on initial inflammatory response – an experimental study. Ceska Slov Farm 2021;70:179–85.
16. Hladkykh F, Chyzh M. Modulation of meloxicam-induced changes in gastrointestinal and motor activity of the stomach by applying placenta cryoextract. Proc Shevchenko Sci Soc Med Sci 2021;64:84–94.
17. Hladkykh FV. Experimental study of the antiulcer effect of cryopreserved placenta extract on a model of acetylsalicylic acid-induced ulcerogenesis. Curr Issues Pharm Med Sci 2021;35:89–94.
18. Hladkykh FV, Koshurba IV, Chyzh MO. Characteristics of the antiulcerogenic activity of cryopreserved placenta extract in acute and chronic lesions of the stomach. Mod Med Technol 2023;1(56):62–8.
19. Koshurba IV, Hladkykh FV, Chyzh MO. Modulation of lipoperoxidation and energy metabolism in the gastric mucosa as a mechanism of placenta cryoextract activity in the healing of stress-induced erosive-ulcerative damage. Gastroenterology 2022;56(3):149–55.
20. Koshurba IV, Hladkykh FV, Chyzh MO, Belochkina IV, Rubleva TV. Hepatotropic effects of triple antiulcer therapy and placenta cryoextract: the role of sex factors in lipoperoxidation. Fiziol Zh 2022;68:25–32.
21. Koshurba IV, Chyzh MO, Hladkykh FV, Belochkina IV. Influence of placenta cryoextract on the liver metabolic and functional state in case of D-galactosamine hepatitis. Innov Biosyst Bioeng 2022;6:64–7.
22. Chyzh MO, Koshurba IV, Marchenko MM, Hladkykh FV, Belochkina IV. Gender determinism of the effect of placenta cryoextract on the hepatotropic effects of esomeprazole, clarithromycin and metronidazole in chronic liver damage. Mod Med Technol 2023;1(56):55–61.
23. Vogel HG. Drug discovery and evaluation: pharmacological assays. Berlin, Heidelberg: Springer Berlin Heidelberg; 2008.
24. Hladkykh FV. Gastrocytoprotective properties of cryopreserved placenta extract in combined action of low temperatures and inhibition of cyclooxygenase. Acta Fac Med Naiss 2022;39:48–56.
25. Hladkykh FV. Anti-inflammatory properties of diclofenac sodium on the background of combined use with cryopreserved placenta extract in the experiment. Probl Cryobiol Cryomed 2021;31:364–7.
26. Ntamo Y, Ziqubu K, Chellan N, Nkambule BB, Nyambuya TM, Mazibuko-Mbeje SE, et al. Drug-induced liver injury: clinical evidence of N-acetyl cysteine protective effects. Oxid Med Cell Longev 2021;2021:3320325. doi: 10.1155/2021/3320325.
27. Asakawa T, Matsushita S. Coloring condition of thiobarbituric acid test for detecting lipid hydroperoxides. Lipids 1980;15:137–40.
28. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121–6.
29. Vink KL, Schuurman W, van Gansewinkel R. Use of the caffeine reagent in direct spectrophotometry of bilirubin. Clin Chem 1986;32:1389–93.
30. 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.
31. Tokuda K. Tanimoto K. New method of measuring serum bilirubin using vanadic acid. Jap J Clin Chem 1993;22:116–22.
32. Zar JH. Biostatistical analysis. 5th edition. Prentice-Hall, Englewood; 2014.
33. Botros M, Sikaris KA. The De Ritis ratio: the test of time. Clin Biochem Rev 2013;34:117-30.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement 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 acknowledgement 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).