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Eucalyptol Protects against Cisplatin-Induced Liver Injury in Rats

  • ANIMAL AND HUMAN PHYSIOLOGY
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Abstract

Eucalyptol (1,8-cineole), a terpenoid oxide, is known as the main component of eucalyptus essential oils. The antimicrobial, anti-inflammatory and antioxidant activities of eucalyptol have been reported in many studies. We investigated the possible effects of eucalyptol (EUC) against hepatotoxicity induced by cisplatin (CIS) in Wistar albino rats. A total of 24 rats were divided into 4 equal groups; Control (C), Eucalyptol (EUC), Cisplatin (CIS), and Cisplatin + Eucalyptol (CIS + EUC). CIS and CIS + EUC groups received cisplatin (12 mg/kg, in a single dose, intraperitoneally (i.p.)). EUC and CIS + EUC groups were treated with eucalyptol (100 mg/kg, seven days, orally). The rats were euthanised under appropriate conditions, and samples were taken. Histopathologically, hepatocyte degeneration and necrosis, sinusoidal dilatation, inflammatory cell infiltration and bile duct proliferation were significantly irregular in the CIS group compared to the C group. However, EUC treatment modulated changes in group CIS. Biochemically, EUC (100 mg/kg) treatment reduced oxidative stress against increased liver hepatotoxicity by decreasing MDA levels and increasing Glutathione (GSH), Glucose-6-phosphate dehydrogenase (G6PD) and Catalase (CAT) levels. EUC treatment down-regulated 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, resulting in reductions DNA damage. It also significantly down-regulated inducible nitric oxide synthase (iNOS) expression. In conclusion, eucalyptol exerts protective effects on cisplatin-induced experimental liver toxicity in rats by improving oxidative stress and oxidative DNA damage and iNOS expressions.

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REFERENCES

  1. Abd Rashid, N., Abd Halim, S.A.S., Teoh, S.L., Budin, S.B., Hussan, F., Ridzuan, N.R.A., and Jalil, N.A.A., The role of natural antioxidants in cisplatin-induced hepatotoxicity, Biomed. Pharmacother., 2021, vol. 144, p. 112328.

    Article  CAS  PubMed  Google Scholar 

  2. Abdel-Daim, M.M., Abdel-Rahman, H.G., Dessouki, A.A., Ali, H., Khodeer, D.M., Bin-Jumah, M., Alhader, M.S., Alkahtani, S., and Aleya, L., Impact of garlic (Allium sativum) oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats, Sci. Total. Environ., 2020, vol. 710, p. 136338.

    Article  CAS  PubMed  Google Scholar 

  3. Aebi, H., Catalase in vitro, Methods Enzymol., 1984, vol. 105, pp. 121–126.

    CAS  PubMed  Google Scholar 

  4. Ahmadipour, A., Sharififar, F., Nakhaipour, F., Samanian, M., and Karami-Mohajeri, S., Hepatoprotective effect of Zataria multiflora Boisson cisplatin-induced oxidative stress in male rat, J. Med. Life Sci., 2015, vol. 8, pp. 275–281.

    CAS  Google Scholar 

  5. Beutler, E., A Manual of Biochemical Methods, New York: Grune and Stratton, 1975, 2rd ed., pp. 112–114.

    Google Scholar 

  6. Bhattacharyya, S. and Mehta, P., The hepatoprotective potential of Spirulina and vitamin C supplemention in cisplatin toxicity, Food Funct., 2012, vol. 3, pp. 164–169.

    Article  CAS  PubMed  Google Scholar 

  7. Cagin, Y.F., Erdogan, M.A., Sahin, N., Parlakpinar, H., Atayan, Y., Polat, A., Vardi, N., Yildiz, A., and Tanbek, K., Protective effects of apocynin on cisplatin-induced hepatotoxicity in rats, Arch. Med. Sci., 2015, vol. 46, pp. 517–526.

    CAS  Google Scholar 

  8. Cai, Z.M., Peng, J.Q., Chen, Y., Tao, L., Zhang, Y.Y., Fu, L.Y., Long, Q.D., and Shen, X.C., 1,8-Cineole: a review of source, biological activities, and application, J. Asian Nat. Prod. Res., 2021, vol. 23, pp. 938–954.

    Article  CAS  PubMed  Google Scholar 

  9. de Oliveira Mora, L., Antunes, L.M.G., Francescato, H.s.D.C., and Bianchi, M.d.L.P., The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats, Pharmacol. Res., 2003, vol. 47, pp. 517–522.

    Article  Google Scholar 

  10. Dkhil, M.A., Al-Quraishy, S., Aref, A.M., Othman, M.S., El-Deib, K.M., and Abdel Moneim, A.E., The potential role of Azadirachta indica treatment on cisplatin-induced hepatotoxicity and oxidative stress in female rats, Oxid. Med. Cell. Longevity, 2013, p. 741817.

  11. Eiserich, J.P., Patel, R.P., and O’Donnell, V.B., Pathophysiology of nitric oxide and related species: free radical reactions and modification of biomolecules, Mol. Asp. Med., 1998, vol. 19, pp. 221–357.

    CAS  Google Scholar 

  12. Ekinci-Akdemir, F.N., Yildirim, S., Kandemir, F.M., Gülçin, İ., Küçükler, S., Sağlam, Y.S., and Yakan, S., The effects of casticin and myricetin on liver damage induced by methotrexate in rats, Iran. J. Basic Med. Sci., 2018, vol. 21, pp. 1281–1288.

    PubMed Central  Google Scholar 

  13. El-Shitany, N.A. and Eid, B., Proanthocyanidin protects against cisplatin-induced oxidative liver damage through inhibition of inflammation and NF-κβ/TLR-4 pathway, Environ. Toxicol., 2017, vol. 32, pp. 1952–1963.

    Article  CAS  PubMed  Google Scholar 

  14. Ellman, G.L., Tissue sulfhydryl groups, Arch. Biochem. Biophys., 1959, vol. 82, pp. 70–77.

    Article  CAS  PubMed  Google Scholar 

  15. Fahmy, M.A., Hassan, E.E., Ibrahim, N.E., Hassan, E.M., Hassan, Z.M., and Omara, E.A., Protective role of ficus carica extract against hepato-testicular side effects and genotoxicity induced by cisplatin, Pharm. J., 2020, vol. 12, pp. 645–656.

    CAS  Google Scholar 

  16. Fazelan, Z., Hoseini, S.M., Yousefi, M., Khalili, M., Hoseinifar, S.H., and Van Doan, H., Effects of dietary eucalyptol administration on antioxidant and inflammatory genes in common carp (Cyprinus carpio) exposed to ambient copper, Aquaculture, 2020, vol. 520, p. 734988.

    Article  CAS  Google Scholar 

  17. Ferah Okkay, I., Okkay, U., Aydin, I.C., Bayram, C., Ertugrul, M.S., Mendil, A.S., and Hacimuftuoglu, A., Centella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxidative stress, inflammation, and apoptosis, Environ. Sci. Pollut. Res., 2022, vol. 29, pp. 33774–33784.

    Article  CAS  Google Scholar 

  18. Gelen, V., Gelen, S.U., Celebi, F., Cinar, A., Yildirim, S., and Eser, G., The protective effect of Lactobacillus rhamnosus, Lactobacillus fermentum and Lactobacillus brevis against cisplatin-induced hepatic damage in rats, Fresenius Environ. Bull., 2019, vol. 28, pp. 7583–7592.

    CAS  Google Scholar 

  19. Graille, M., Wild, P., Sauvain, J.-J., Hemmendinger, M., Guseva Canu, I., and Hopf, N.B., Urinary 8-OHdG as a biomarker for oxidative stress: a systematic literature review and meta-analysis, Int. J. Mol. Sci., 2020, vol. 21, p. 3743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hanigan, M.H. and Devarajan, P., Cisplatin nephrotoxicity: molecular mechanisms, Cancer Ther., 2003, vol 1, pp. 47–61.

    PubMed  PubMed Central  Google Scholar 

  21. Ishikawa, T., Future perspectives on the treatment of hepatocellular carcinoma with cisplatin, World J. Hepatol., 2009, vol. 1, pp. 8–16.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Iwakiri, Y., Nitric oxide in liver fibrosis: the role of inducible nitric oxide synthase, Clin. Mol. Hepatol., 2015, vol. 21, pp. 319–325.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kazak, F., Deveci, M.Z.Y., and Akçakavak, G., Eucalyptol alleviates cisplatin-induced kidney damage in rats, Drug. Chem. Toxicol., 2022, pp. 1–8.

  24. Kazak, F., in Functional Foods and Nutraceuticals: Bioactive Compounds, Haci Ahmet Deveci, Ed., France: Livre de Lyon, 2022, pp. 125–138.

    Google Scholar 

  25. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R., Protein measurement with pholin phenol reagent, J. Biol. Chem., 1951, vol. 193, pp. 265–275.

    Article  CAS  PubMed  Google Scholar 

  26. Mansour, H.H., Hafez, H.F., and Fahmy, N.M., Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats, BMB Rep., 2006, vol. 39, pp. 656–661.

    Article  CAS  Google Scholar 

  27. Martins, N., Santos, N., Curti, C., Bianchi, M., and Santos, A., Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver, J. Appl. Toxıcol., 2008, vol. 28, pp. 337–344.

    Article  CAS  PubMed  Google Scholar 

  28. Mesgari Abbasi, M., Hassanalilou, T., Khordadmehr, M., Mohammadzadeh Vardin, A., Behroozi Kohlan, A., and Khalili, L., Effects of Cornus mas fruit hydro-methanolic extract on liver antioxidants and histopathologic changes induced by cisplatin in rats, Indian J. Clin. Biochem., 2020, vol. 35, pp. 218–224.

    Article  CAS  PubMed  Google Scholar 

  29. Natarajan, A., Jayavelu, A., Thangamani, R., Prabakarakrishnan, R., Choi, D., Mohammed, A., Khamis, H., and Kumar, B.S., In vivo evaluation of protective effect of Sargassum fusiforme on cisplatin induced hepato-renal toxicity, Physiol. Mol. Plant. Pathol., 2022, vol. 117, p. 101748.

    Article  CAS  Google Scholar 

  30. Nathan, C., Nitric oxide as a secretory product of mammalian cells, FASEB J., 1992, vol. 6, pp. 3051–3064.

    Article  CAS  PubMed  Google Scholar 

  31. Ohkawa, H., Ohishi, N., and Yagi, K., Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction, Anal. Biochem., 1979, vol 95, pp. 351–358.

    Article  CAS  PubMed  Google Scholar 

  32. Palipoch, S., Punsawad, C., Koomhin, P., and Suwannalert, P., Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress, BMC Complement, Altern. Med., 2014, vol 14, pp. 1–8.

    Article  Google Scholar 

  33. Pınar, N., Çakırca, G., Hakverdi, S., and Kaplan, M., Protective effect of alpha lipoic acid on cisplatin induced hepatotoxicity in rats, Biotech. Histochem., 2020, vol. 95, pp. 219–224.

    Article  PubMed  Google Scholar 

  34. Rabik, C.A. and Dolan, M.E., Molecular mechanisms of resistance and toxicity associated with platinating agents, Cancer Treat. Rev., 2007, vol. 33, pp. 9–23.

    Article  CAS  PubMed  Google Scholar 

  35. Radi, R., Nitric oxide, oxidants, and protein tyrosine nitration, Proc. Natl. Acad. Sci. U. S. A., 2004, vol. 101, pp. 4003–4008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Santos, F. and Rao, V., Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils. Phytotherapy research, J. Pharmacol. Toxicol. Methods, 2000, vol. 14, pp. 240–244.

    CAS  Google Scholar 

  37. Seol, G.H. and Kim, K.Y., Eucalyptol and its role in chronic diseases, Nat. Rev. Drug. Discov., 2016, pp. 389–398.

  38. Srivastava, R., Farookh, A., Ahmad, N., Misra, M., Hasan, S., and Husain, M., Evidence for the involvement of nitric oxide in cisplatin-induced toxicity in rats, Biometals, 1996, vol. 9, pp. 139–142.

    Article  CAS  PubMed  Google Scholar 

  39. Sueda, T., Kazak, F., Peker, P., and Kisaçam, M.A., Rutin attenuates methotrexate-induced hepatic oxidative stress in rats, Ataturk Univ. Vet. Bilim. Derg., 2021, vol. 16, pp. 291–297.

    Google Scholar 

  40. Tahoun, E., Elgedawy, G., and El-Bahrawy, A., Cytoprotective effect of ginger extract on cisplatin-induced hepatorenal toxicity in rats via modulation of oxidative stress, inflammation and apoptosis: histopathological, biochemical and immunohistochemical study, Comp. Clin. Pathol., 2021, vol. 30, pp. 647–663.

    Article  CAS  Google Scholar 

  41. Xu, G., Guo, J., and Sun, C., Eucalyptol ameliorates early brain injury after subarachnoid haemorrhage via antioxidant and anti-inflammatory effects in a rat model, Pharm. Biol., 2021, vol. 59, pp. 112–118.

    Article  Google Scholar 

  42. Yu, W., Chen, Y., Dubrulle, J., Stossi, F., Putluri, V., Sreekumar, A., Putluri, N., Baluya, D., Lai, S.Y., and Sandulache, V.C., Cisplatin generates oxidative stress which is accompanied by rapid shifts in central carbon metabolism, Sci. Rep., 2018, vol. 8, pp. 1–12.

    Google Scholar 

  43. Zicca, A., Cafaggi, S., Mariggiò, M.A., Vannozzi, M.O., Ottone, M., Bocchini, V., Caviglioli, G., and Viale, M., Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in rats, Eur J. Pharmacol., 2002 vol. 442, pp. 265–272.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Gokhan Akcakavak.

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Statement on the welfare of animals. This study was approved by The Hatay Mustafa Kemal University Local Ethical Committee (Approval no: 2022/06-18, 18.11.2022).

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Gokhan Akcakavak, Kazak, F. & Yilmaz Deveci, M.Z. Eucalyptol Protects against Cisplatin-Induced Liver Injury in Rats. Biol Bull Russ Acad Sci 50, 987–994 (2023). https://doi.org/10.1134/S106235902360085X

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