Effects of gossypin on acetaminophen-induced hepatotoxicity in mice

Yıl 2024, Cilt: 25 Sayı: 1, 81 - 90, 15.04.2024

İrfan Çınar , Muhammed Yayla , Erdem Toktay , Damla Binnetoğlu

https://doi.org/10.23902/trkjnat.1410800

Öz

Liver injury from paracetamol (acetaminophen) (APAP) is common worldwide. To prevent intoxication with a drug with high poisoning, treatment can be made possible with an easily accessible and harmless substance. This study aimed to investigate the hepatoprotective ef-fects of Gossypin (GOS) in mice exposed to an overdose of APAP -the possible mechanism of action. Specifically, serum [alanine aminotransferase (ALT), aspartate transaminase (AST), and hepatic biochemical parameters (glutathione (GSH), malondialdehyde (MDA) and super-oxide dismutase (SOD)] were evaluated. Protein and mRNA levels of inflammatory, apoptot-ic, and cytochrome factors, including TNF-α, IL-1β, IL-6, NF-kB, and CYP2E1, were ana-lyzed using real-time PCR. Pretreatment with GOS significantly reduced APAP-induced he-patic injury via oxidative stress. Along with potent antioxidant activity, GOS promoted APAP hepatic detoxification by regulating AST, ALT, GSH, MDA, and SOD activities and mRNA levels of the cytochrome CYP2E1 gene. The anti-inflammatory activity of GOS in-creases its production. TNF-α, IL-1β and IL-6, through possible NF-kB blockade, are also responsible for its hepatoprotective effect. Taken together, GOS has the potential to be devel-oped as a preventive agent to be administered to patients suffering from APAP overdose.

Anahtar Kelimeler

Gossypin, Acetaminophen, CYP2E1, AST, NF-kB, Anti-oxidative

Etik Beyan

Ethics committee approval was received for this study from the Kafkas University Local Animal Care Committee by the number KAU-HADYEK/2019-071.

Destekleyen Kurum

Science and Technology Research Projects of Kastamonu University

Proje Numarası

KÜ-BAP01/2021-6

Kaynakça

• 1. Aycan, I.O., Tufek, A., Tokgoz, O., Evliyaoglu, O., Firat, U., Kavak, G.O., Turgut, H. & Yuksel, M.U. 2014. Thymoquinone treatment against acetaminophen-induced hepatotoxicity in rats. International journal of surgery, 12(3): 213-218. https://doi.org/10.1016/j.ijsu.2013.12.013
• 2. Babu, B.H., Jayram, H.N., Nair, M.G., Ajaikumar, K.B. & Padikkala, J. 2003. Free radical scavenging, antitumor and anticarcinogenic activity of gossypin. Journal of experimental & clinical cancer research: CR, 22(4): 581-589. https://pubmed.ncbi.nlm.nih.gov/15053300/
• 3. Bromer, M.Q. & Black, M. 2003. Acetaminophen hepatotoxicity. Clinics in liver disease, 7(2): 351-367. https://doi.org/10.1016/S1089-3261(03)00025-4
• 4. Bunchorntavakul, C. & Reddy, K.R. 2013. Acetaminophen-related hepatotoxicity. Clinics in liver disease, 17(4): 587-607. https://doi.org/10.1016/j.cld.2013.07.005
• 5. Cadirci, E., Ugan, R.A., Dincer, B., Gundogdu, B., Cinar, I., Akpinar, E. & Halici, Z. 2019. Urotensin receptors as a new target for CLP induced septic lung injury in mice. Naunyn-Schmiedeberg's archives of pharmacology, 392(2): 135-145. https://doi.org/10.1007/s00210-018-1571-8
• 6. Cinar, I. 2021. Apoptosis-Inducing Activity and Antiproliferative Effect of Gossypin on PC-3 Prostate Cancer Cells. Anti-cancer agents in medicinal chemistry, 21(4): 445-450. https://doi.org/10.2174/1871520620666200721103422
• 7. Cinar, I., Sirin, B., Aydin, P., Toktay, E., Cadirci, E., Halici, I. & Halici, Z. 2019. Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. Life sciences, 221: 327-334. https://doi.org/10.1016/j.lfs.2019.02.039
• 8. Cinar, I., Yayla, M., Tavaci, T., Toktay, E., Ugan, R.A., Bayram, P. & Halici, H. 2022. In Vivo and In Vitro Cardioprotective Effect of Gossypin Against Isoproterenol-Induced Myocardial Infarction Injury. Cardiovascular toxicology, 22(1): 52-62. https://doi.org/.1007/s12012-021-09698-3
• 9. Dincer, B., Cinar, I., Yayla, M. & Toktay, E. 2022. Evaluation of the protective effects of gossypin for ischemia/reperfusion injury in ovary tissue. The journal of obstetrics and gynaecology research, 48(3): 748-756. https://doi.org/10.1111/jog.15127
• 10. Dong, D., Xu, L., Han, X., Qi, Y., Xu, Y., Yin, L., Liu, K. & Peng, J. 2014. Effects of the total saponins from Rosa laevigata Michx fruit against acetaminophen-induced liver damage in mice via induction of autophagy and suppression of inflammation and apoptosis. Molecules, 19(6): 7189-7206. https://doi.org/10.3390/molecules19067189
• 11. Ferah, I., Halici, Z., Bayir, Y., Demirci, E., Unal, B. & Cadirci, E. 2013. The role of infliximab on paracetamol-induced hepatotoxicity in rats. Immunopharmacology and immunotoxicology, 35(3): 373-381. https://doi.org/10.3109/08923973.2013.775589
• 12. Ferrucci, L.M., Bell, B.P., Dhotre, K.B., Manos, M.M., Terrault, N.A., Zaman, A., Murphy, R.C., Vanness, G.R., Thomas, A.R., Bialek, S.R., Desai, M.M. & Sofair, A.N. 2010. Complementary and alternative medicine use in chronic liver disease patients. Journal of clinical gastroenterology, 44(2): e40-45. https://doi.org/10.1097/MCG.0b013e3181b766ed
• 13. Gautam, P. & Flora, S.J. 2010. Oral supplementation of gossypin during lead exposure protects alteration in heme synthesis pathway and brain oxidative stress in rats. Nutrition, 26(5): 563-570. https://doi.org/10.1016/j.nut.2009.06.008
• 14. Gilroy, D.W., Lawrence, T., Perretti, M. & Rossi, A.G. 2004. Inflammatory resolution: new opportunities for drug discovery. Nature reviews. Drug discovery, 3(5): 401-416. https://doi.org/10.1038/nrd1383
• 15. Golestan Jahromi, M., Nabavizadeh, F., Vahedian, J., Nahrevanian, H., Dehpour, A.R. & Zare-Mehrjardi, A. 2010. Protective effect of ghrelin on acetaminophen-induced liver injury in rat. Peptides, 31(11): 2114-2117. https://doi.org/10.1016/j.peptides.2010.08.009
• 16. Holubek, W.J., Kalman, S. & Hoffman, R.S. 2006. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology, 43(4): 880; author reply 882. https://doi.org/10.1002/hep.21106
• 17. Karakus, E., Halici, Z., Albayrak, A., Polat, B., Bayir, Y., Kiki, I., Cadirci, E., Topcu, A. & Aksak, S. 2013. Agomelatine: an antidepressant with new potent hepatoprotective effects on paracetamol-induced liver damage in rats. Human & experimental toxicology, 32(8): 846-857. https://doi.org/10.1177/0960327112472994
• 18. Katary, M. & Salahuddin, A. 2017. Ameliorative effect of gossypin against gentamicin-induced nephrotoxicity in rats. Life sciences, 176: 75-81. https://doi.org/10.1016/j.lfs.2017.03.009
• 19. Kim, M.S. & Lee, D.Y. 2015. Insulin-like growth factor binding protein-3 enhances etoposide-induced cell growth inhibition by suppressing the NF-kappaB activity in gastric cancer cells. Molecular and cellular biochemistry, 403(1-2): 107-113. https://doi.org/10.3978/j.issn.2304-3881.2014.11.01
• 20. Krenkel, O., Mossanen, J.C. & Tacke, F. 2014. Immune mechanisms in acetaminophen-induced acute liver failure. Hepatobiliary surgery and nutrition, 3(6): 331-343. https://doi.org/10.3978/j.issn.2304-3881.2014.11.01
• 21. La Rosa, F.A., Pierce, J.W. & Sonenshein, G.E. 1994. Differential regulation of the c-myc oncogene promoter by the NF-kappa B rel family of transcription factors. Molecular and cellular biology, 14(2): 1039-1044. https://doi.org/10.1128/mcb.14.2.1039-1044.1994
• 22. Larsen, F.S. & Wendon, J. 2014. Understanding paracetamol-induced liver failure. Intensive care medicine, 40(6): 888-890. https://doi: 10.1007/s00134-014-3293-9
• 23. Li, G., Chen, J.B., Wang, C., Xu, Z., Nie, H., Qin, X.Y., Chen, X.M. & Gong, Q. 2013. Curcumin protects against acetaminophen-induced apoptosis in hepatic injury. World journal of gastroenterology, 19(42): 7440-7446. https://doi.org/10.3748/wjg.v19.i42.7440
• 24. Liang, B., Guo, X.L., Jin, J., Ma, Y.C. & Feng, Z.Q. 2015. Glycyrrhizic acid inhibits apoptosis and fibrosis in carbon-tetrachloride-induced rat liver injury. World journal of gastroenterology, 21(17): 5271-5280. https://doi.org/10.3748/wjg.v21.i17.5271
• 25. Livak, K.J. & Schmittgen, T.D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25(4): 402-408. https://doi.org/10.1006/meth.2001.1262
• 26. Madrigal-Santillan, E., Madrigal-Bujaidar, E., Alvarez-Gonzalez, I., Sumaya-Martinez, M.T., Gutierrez-Salinas, J., Bautista, M., Morales-Gonzalez, A., Garcia-Luna y Gonzalez-Rubio, M., Aguilar-Faisal, J.L. & Morales-Gonzalez, J.A. 2014. Review of natural products with hepatoprotective effects. World journal of gastroenterology, 20(40): 14787-14804. https://doi.org/10.3748/wjg.v20.i40.14787
• 27. Matic, M.M., Paunovic, M.G., Milosevic, M.D., Ognjanovic, B.I. & Saicic, Z.S. 2021. Hematoprotective effects and antioxidant properties of beta-glucan and vitamin C against acetaminophen-induced toxicity: an experimental study in rats. Drug and chemical toxicology, 44(3): 302-309. https://doi.org/10.1080/01480545.2019.1587451
• 28. McGill, M.R. & Jaeschke, H. 2013. Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharmaceutical research, 30(9): 2174-2187. https://doi.org/10.1007/s11095-013-1007-6
• 29. Palabiyik, S.S., Karakus, E., Akpinar, E., Halici, Z., Bayir, Y., Yayla, M. & Kose, D. 2016. The Role of Urotensin Receptors in the Paracetamol-Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist. Basic & clinical pharmacology & toxicology, 118(2): 150-159. https://doi.org/10.1111/bcpt.12447
• 30. Raffa, R.B., Pergolizzi, J.V., Jr., Taylor, R., Jr., Decker, J.F. & Patrick, J.T. 2014. Acetaminophen (paracetamol) oral absorption and clinical influences. Pain practice: the official journal of World Institute of Pain, 14(7): 668-677. https://doi.org/10.1111/papr.12130
• 31. Roomi, M.W., Kalinovsky, T., Ivanov, V., Rath, M. & Niedzwiecki, A. 2008. A nutrient mixture prevents acetaminophen hepatic and renal toxicity in ICR mice. Human & experimental toxicology, 27(3): 223-230. https://doi.org/10.1177/0960327108090276
• 32. Rotundo, L. & Pyrsopoulos, N. 2020. Liver injury induced by paracetamol and challenges associated with intentional and unintentional use. World journal of hepatology, 12(4): 125-136. https://doi.org/10.4254/wjh.v12.i4.125
• 33. Song, E., Fu, J., Xia, X., Su, C. & Song, Y. 2014. Bazhen decoction protects against acetaminophen induced acute liver injury by inhibiting oxidative stress, inflammation and apoptosis in mice. PloS one, 9(9): e107405. https://doi.org/10.1371/journal.pone.0107405
• 34. Toktay, E., Selli, J., Gurbuz, M.A., Tastan, T.B., Ugan, R.A., Un, H. & Halici, Z. 2020. Effects of soy isoflavonoids (genistein and daidzein) on endometrial receptivity. Iranian journal of basic medical sciences, 23(12): 1603-1609. https://doi.org/10.22038/ijbms.2020.48294.11089
• 35. Ugan, R.A., Cadirci, E., Halici, Z., Toktay, E. & Cinar, I. 2018. The role of urotensin-II and its receptors in sepsis-induced lung injury under diabetic conditions. European journal of pharmacology, 818: 457-469. https://doi.org/10.1016/j.ejphar.2017.11.011
• 36. Wu, Y.L., Jiang, Y.Z., Jin, X.J., Lian, L.H., Piao, J.Y., Wan, Y., Jin, H.R., Joon Lee, J. & Nan, J.X. 2010. Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen-induced hepatic toxicity in mice. Phytomedicine: international journal of phytotherapy and phytopharmacology, 17(6): 475-479. https://doi.org/10.1016/j.phymed.2009.07.011
• 37. Yapar, K., Kart, A., Karapehlivan, M., Atakisi, O., Tunca, R., Erginsoy, S. & Citil, M. 2007. Hepatoprotective effect of L-carnitine against acute acetaminophen toxicity in mice. Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie, 59(2): 121-128. https://doi.org/10.1016/j.etp.2007.02.009