Lavender (Lavandula officinalis) essential oil prevents acetaminophen-induced hepatotoxicity by decreasing oxidative stress and inflammatory response




Acute Hepatic Injury; Lavender Essential Oil; Oxidative Stress; Antioxidant; Hepatotoxicity.


Acetaminophen (N-acetyl-p-aminophenol, APAP) is the most popular drug recommended and consumed for relieving mild and moderate pain and fever. Although effective in therapeutic doses, APAP overdose induces hepatotoxicity, causing acute liver failure. In this study, the hepatoprotective effects and the underlying mechanisms of Lavandula officinalis essential oil (LEO) were investigated in APAP-induced hepatotoxicity. To evaluate the hepatoprotective effect, Balb /c mice were pretreated with LEO at doses of 200 and 400 mg/kg, once daily for seven days. On the seventh day, mice were treated with APAP (250 mg/kg) to induce hepatotoxicity. LEO significantly decreased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γ-GT) compared to the APAP group. Besides, a decrease in myeloperoxidase (MPO) activity, nitric oxide (NO), and pro-inflammatory cytokines levels were observed in liver samples of the LEO treated mice. Moreover, pretreatment with LEO showed significant antioxidant activity by decreasing the levels of malondialdehyde (MDA), carbonylated proteins, reactive oxygen species (ROS), and glutathione (GSH), in addition to increasing levels of the hepatic superoxide dismutase (SOD), catalase (CAT), and oxidized glutathione (GSSG). Our results showed that LEO improved liver functions altered by APAP by inhibiting oxidative stress and inflammatory induced by APAP and other oxidative stress-mediated toxicities.


Abdallah, H. M. I., Abdel-Rahman, R. F., El Awdan, S. A., Allam, R. M., El-Mosallamy, A. E. M. K., Selim, M. S., Mohamed, S. S., Arbid, M. S., & Farrag, A. R. H. (2019). Protective effect of some natural products against chemotherapy-induced toxicity in rats. Heliyon, 5(5), e01590.

Adams, R. P. (2007). Identification of Essential Oil Components By Gas Chromatography/ Mass Spectrometry (C. Stream. (ed.); 4th Editio). Allured Publishing Corporation.

Aebi, H. (1984). Catalase in vitro. Methods Enzymol, 121–612.

Ames-Sibin, A. P., Barizão, C. L., Castro-Ghizoni, C. V., Silva, F. M. S., Sá-Nakanishi, A. B., Bracht, L., Bersani-Amado, C. A., Marçal-Natali, M. R., Bracht, A., & Comar, J. F. (2018). β-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats. Journal of Cellular Biochemistry, 119(12), 10262–10277.

Arauz, J., Ramos-Tovar, E., & Muriel, P. (n.d.). Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside. Annals of Hepatology, 15(2), 160–173.

Athersuch, T. J., Antoine, D. J., Boobis, A. R., Coen, M., Daly, A. K., Possamai, L., Nicholson, J. K., & Wilson, I. D. (2018). Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective. Toxicology Research, 7(3), 347–357.

Blieden, M., Paramore, L. C., Shah, D., & Ben-Joseph, R. (2014). A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States. Expert Review of Clinical Pharmacology, 7(3), 341–348.

Bradley, P. P., Priebat, D. A., Christensen, R. D., & Rothstein, G. (1982). Measurement of Cutaneous Inflammation: Estimation of Neutrophil Content with an Enzyme Marker. Journal of Investigative Dermatology, 78(3), 206–209.

Buege, J. A., & Aust, S. D. (1978). Microsomal lipid peroxidation. In Methods in Enzymology. pp. 302–310.

Cao, L., Waldon, D., Teffera, Y., Roberts, J., Wells, M., Langley, M., & Zhao, Z. (2013). Ratios of biliary glutathione disulfide (GSSG) to glutathione (GSH): a potential index to screen drug-induced hepatic oxidative stress in rats and mice. Analytical and Bioanalytical Chemistry, 405(8), 2635–2642.

Cardia, G. F. E., Silva-Filho, S. E., Silva, E. L., Uchida, N. S., Cavalcante, H. A. O., Cassarotti, L. L., Salvadego, V. E. C., Spironello, R. A., Bersani-Amado, C. A., & Cuman, R. K. N. (2018). Effect of Lavender (Lavandula angustifolia) Essential Oil on Acute Inflammatory Response. Evidence-Based Complementary and Alternative Medicine, 2018, 1–10.

Casas-Grajales, S. (2015). Antioxidants in liver health. World Journal of Gastrointestinal Pharmacology and Therapeutics, 6(3), 59.

Chen, Y., Dong, H., Thompson, D. C., Shertzer, H. G., Nebert, D. W., & Vasiliou, V. (2013). Glutathione defense mechanism in liver injury: Insights from animal models. Food and Chemical Toxicology, 60, 38–44.

Chiu, Y.-J., Chou, S.-C., Chiu, C.-S., Kao, C.-P., Wu, K.-C., Chen, C.-J., Tsai, J.-C., & Peng, W.-H. (2018). Hepatoprotective effect of the ethanol extract of Polygonum orientale on carbon tetrachloride-induced acute liver injury in mice. Journal of Food and Drug Analysis, 26(1), 369–379.

Ciftci, O., Ozdemir, I., Tanyildizi, S., Yildiz, S., & Oguzturk, H. (2011). Antioxidative effects of curcumin, β-myrcene and 1,8-cineole against 2,3,7,8-tetrachlorodibenzo- p -dioxin-induced oxidative stress in rats liver. Toxicology and Industrial Health, 27(5), 447–453.

da Rocha, B. A., Ritter, A. M. V., Ames, F. Q., Gonçalves, O. H., Leimann, F. V., Bracht, L., Natali, M. R. M., Cuman, R. K. N., & Bersani-Amado, C. A. (2017). Acetaminophen-induced hepatotoxicity: Preventive effect of trans anethole. Biomedicine & Pharmacotherapy, 86, 213–220.

Du, K., Ramachandran, A., & Jaeschke, H. (2016). Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential. Redox Biology, 10, 148–156.

Dutta, S., Majzoub, A., & Agarwal, A. (2019). Oxidative stress and sperm function: A systematic review on evaluation and management. Arab Journal of Urology, 17(2), 87–97.

Edris, A. E. (2007). Pharmaceutical and therapeutic Potentials of essential oils and their individual volatile constituents: a review. Phytotherapy Research, 21(4), 308–323.

El-Hosseiny, L. S., Alqurashy, N. N., & Sheweita, S. A. (2016). Oxidative Stress Alleviation by Sage Essential Oil in Co-amoxiclav induced Hepatotoxicity in Rats. International Journal of Biomedical Science, 12(2), 71–78.

Eugenio-Pérez, D., Montes de Oca-Solano, H. A., & Pedraza-Chaverri, J. (2016). Role of food-derived antioxidant agents against acetaminophen-induced hepatotoxicity. Pharmaceutical Biology, 54(10), 2340–2352.

Freitag, A. F., Cardia, G. F. E., Da Rocha, B. A., Aguiar, R. P., Silva-Comar, F. M. D. S., Spironello, R. A., Grespan, R., Caparroz-Assef, S. M., Bersani-Amado, C. A., & Cuman, R. K. N. (2015). Hepatoprotective effect of silymarin (silybum marianum) on hepatotoxicity induced by acetaminophen in spontaneously hypertensive rats. Evidence-Based Complementary and Alternative Medicine.

Ghanem, C. I., Pérez, M. J., Manautou, J. E., & Mottino, A. D. (2016). Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity. Pharmacological Research, 109, 119–131.

Grespan, R., Aguiar, R. P., Giubilei, F. N., Fuso, R. R., Damião, M. J., Silva, E. L., Mikcha, J. G., Hernandes, L., Bersani Amado, C., & Cuman, R. K. N. (2014). Hepatoprotective Effect of Pretreatment with Thymus vulgaris Essential Oil in Experimental Model of Acetaminophen-Induced Injury. Evidence-Based Complementary and Alternative Medicine, 1–8.

Hinson, J. A., Roberts, D. W., & James, L. P. (2010). Mechanisms of Acetaminophen-Induced Liver Necrosis (pp. 369–405).

Hissin, P. J., & Hilf, R. (1976). A fluorometric method for determination of oxidized and reduced glutathione in tissues. Analytical Biochemistry, 74(1), 214–226.

Jiang, Z., Guo, X., Zhang, K., Sekaran, G., Cao, B., Zhao, Q., Zhang, S., Kirby, G. M., & Zhang, X. (2019). The Essential Oils and Eucalyptol From Artemisia vulgaris L. Prevent Acetaminophen-Induced Liver Injury by Activating Nrf2-Keap1 and Enhancing APAP Clearance Through Non-Toxic Metabolic Pathway. Frontiers in Pharmacology, 10, 782.

Juergens, U. R., Stöber, M., & Vetter, H. (1998). Inhibition of cytokine production and arachidonic acid metabolism by eucalyptol (1.8-cineole) in human blood monocytes in vitro. European Journal of Medical Research, 3(11), 508–510.

Khan, A., Vaibhav, K., Javed, H., Tabassum, R., Ahmed, M. E., Khan, M. M., Khan, M. B., Shrivastava, P., Islam, F., Siddiqui, M. S., Safhi, M. M., & Islam, F. (2014). 1,8-Cineole (Eucalyptol) Mitigates Inflammation in Amyloid Beta Toxicated PC12 Cells: Relevance to Alzheimer’s Disease. Neurochemical Research, 39(2), 344–352.

Khayyat, A., Tobwala, S., Hart, M., & Ercal, N. (2016). N -acetylcysteine amide, a promising antidote for acetaminophen toxicity. Toxicology Letters, 241, 133–142.

Kumari, A., & Kakkar, P. (2012). Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade. Life Sciences, 90(15–16), 561–570.

Lee, W. M. (2017). Acetaminophen (APAP) hepatotoxicity—Isn’t it time for APAP to go away? Journal of Hepatology, 67(6), 1324–1331.

Levine, R. L., Garland, D., Oliver, C. N., Amici, A., Climent, I., Lenz, A.-G., Ahn, B.-W., Shaltiel, S., & Stadtman, E. R. (1990). Determination of carbonyl content in oxidatively modified proteins. Methods in Enzymology, 464–478.

Liang, H., Feng, Y., Cui, R., Qiu, M., Zhang, J., & Liu, C. (2018). Simvastatin protects against acetaminophen-induced liver injury in mice. Biomedicine & Pharmacotherapy, 98, 916–924.

Marklund, s., & Marklund, g. (1974). Involvement of the Superoxide Anion Radical in the Autoxidation of Pyrogallol and a Convenient Assay for Superoxide Dismutase. European Journal of Biochemistry, 47(3), 469–474.

Mori, H.-M., Kawanami, H., Kawahata, H., & Aoki, M. (2016). Wound healing potential of lavender oil by acceleration of granulation and wound contraction through induction of TGF-β in a rat model. BMC Complementary and Alternative Medicine, 16(1), 144.

Niksic, H., Kovac-Besovic, E., Omeragic, E., Muratovic, S., Kusturica, J., & Duric, K. (2017). Antiproliferative, antimicrobial, and antioxidant activity of Lavandula angustifolia Mill. essential oil. Journal of Health Sciences, 7(1), 35–43.

Papackova, Z., Heczkova, M., Dankova, H., Sticova, E., Lodererova, A., Bartonova, L., Poruba, M., & Cahova, M. (2018). Silymarin prevents acetaminophen-induced hepatotoxicity in mice. Plos one, 13(1), e0191353.

Pinho, R., Aguiar, R., Spironello, R., Silva-Comar, F., Silva-Filho, S., Nogami, E., Bersani-Amado, C., & Cuman, R. (2014). Hepatoprotective Effect of Pretreatment with Rosemary and Ginger Essential Oil in Experimental Model of Acetaminophen-induced Injury. British Journal of Pharmaceutical Research, 4(18), 2126–2135

Rašković, A., Milanović, I., Pavlović, N., Ćebović, T., Vukmirović, S., & Mikov, M. (2014). Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential. BMC Complementary and Alternative Medicine, 14(1), 225.

Robles-Diaz, M., Garcia-Cortes, M., Medina-Caliz, I., Gonzalez-Jimenez, A., Gonzalez-Grande, R., Navarro, J. M., Castiella, A., Zapata, E. M., Romero-Gomez, M., Blanco, S., Soriano, G., Hidalgo, R., Ortega-Torres, M., Clavijo, E., Bermudez-Ruiz, P. M., Lucena, M. I., & Andrade, R. J. (2015). The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity. Liver International, 35(11), 2474–2482.

Rodrigues Siqueira, I., Fochesatto, C., da Silva Torres, I. L., Dalmaz, C., & Alexandre Netto, C. (2005). Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of Wistar rats. Life Sciences, 78(3), 271–278.

Saito, C., Lemasters, J. J., & Jaeschke, H. (2010). c-Jun N-terminal kinase modulates oxidant stress and peroxynitrite formation independent of inducible nitric oxide synthase in acetaminophen hepatotoxicity. Toxicology and Applied Pharmacology, 246(1–2), 8–17.

Santos, F. (2004). 1,8-cineole (eucalyptol), a monoterpene oxide attenuates the colonic damage in rats on acute TNBS-colitis. Food and Chemical Toxicology, 42(4), 579–584.

Santos, F A, & Rao, V. S. (2000). Anti-inflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils. Phytotherapy Research, 14(4), 240–244.

Santos, Flávia A., Silva, R. M., Tomé, A. R., Rao, V. S. N., Pompeu, M. M. L., Teixeira, M. J., De Freitas, L. A. R., & De Souza, V. L. (2001). 1,8-Cineole protects against liver failure in an in-vivo murine model of endotoxemic shock. Journal of Pharmacy and Pharmacology, 53(4), 505–511.

Selmi, S., Jallouli, M., Gharbi, N., & Marzouki, L. (2015). Hepatoprotective and Renoprotective Effects of Lavender (Lavandula stoechas L.) Essential Oils Against Malathion-Induced Oxidative Stress in Young Male Mice. Journal of Medicinal Food, 18(10), 1103–1111. 30

Shan, S., Shen, Z., & Song, F. (2018). Autophagy and acetaminophen-induced hepatotoxicity. Archives of Toxicology, 92(7), 2153–2161.

Silva-Comar, F. M. de S., Wiirzler, L. A. M., Silva-Filho, S. E., Kummer, R., Pedroso, R. B., Spironello, R. A., Silva, E. L., Bersani-Amado, C. A., & Cuman, R. K. N. (2014). Effect of Estragole on Leukocyte Behavior and Phagocytic Activity of Macrophages. Evidence-Based Complementary and Alternative Medicine, 1–7.

Silva-Filho, S., De Souza Silva-Comar, F., Wiirzler, L., Do Pinho, R., Grespan, R., Bersani-Amado, C., & Cuman, R. (2015). Effect of Camphor on the Behavior of Leukocytes In vitro and In vivo in Acute Inflammatory Response. Tropical Journal of Pharmaceutical Research, 13(12), 2031.

Silva, G. L., Luft, C., Lunardelli, A., Amaral, R. H., Melo, D. A., Donadio, M. V. F., Nunes, F. B., Azambuja, M. S., Santana, J. C., Moraes, C. M. B., Mello, R. O., Cassel, E., Pereira, M. A. de A., & de Oliveira, J. R. (2015). Antioxidant, analgesic and anti-inflammatory effects of lavender essential oil. Anais Da Academia Brasileira de Ciências, 87(2 Suppl), 1397–1408.

Sparkman, O. D. (2005). Identification of essential oil components by gas chromatography/quadrupole mass spectroscopy Robert P. Adams. Journal of the American Society for Mass Spectrometry, 16(11), 1902–1903.

Subramanya, S., Venkataraman, B., Meeran, M., Goyal, S., Patil, C., & Ojha, S. (2018). Therapeutic Potential of Plants and Plant Derived Phytochemicals against Acetaminophen-Induced Liver Injury. International Journal of Molecular Sciences, 19(12), 3776.

Sumalan, R. M., Kuganov, R., Obistioiu, D., Popescu, I., Radulov, I., Alexa, E., Negrea, M., Salimzoda, A. F., Sumalan, R. L., & Cocan, I. (2020). Assessment of Mint, Basil, and Lavender Essential Oil Vapor-Phase in Antifungal Protection and Lemon Fruit Quality. Molecules, 25(8).

Tezcan, A. H., Ozturk, O., Ustebay, S., Adali, Y., & Yagmurdur, H. (2018). The beneficial effects of ozone therapy in acetaminophen-induced hepatotoxicity in mice. Pharmacological Reports, 70(2), 340–345.

Uchida, N.S., Silva-Filho, S. E., Cardia, G. F. E., Cremer, E., De Souza Silva-Comar, F. M., Silva, E. L., Bersani-Amado, C. A., & Cuman, R. K. N. (2017). Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice. Evidence-Based Complementary and Alternative Medicine.

Uchida, Nancy Sayuri, Silva-Filho, S. E., Aguiar, R. P., Wiirzler, L. A. M., Cardia, G. F. E., Cavalcante, H. A. O., Silva-Comar, F. M. de S., Becker, T. C. A., Silva, E. L., Bersani-Amado, C. A., & Cuman, R. K. N. (2017). Protective Effect of Cymbopogon citratus Essential Oil in Experimental Model of Acetaminophen-Induced Liver Injury. The American Journal of Chinese Medicine, 45(03), 515–532.

van Den Dool, H., & Dec. Kratz, P. (1963). A generalization of the retention index system including linear temperature programmed gas—liquid partition chromatography. Journal of Chromatography A, 11, 463–471.

Wang, D., Yuan, X., Liu, T., Liu, L., Hu, Y., Wang, Z., & Zheng, Q. (2012). Neuroprotective Activity of Lavender Oil on Transient Focal Cerebral Ischemia in Mice. Molecules, 17(8), 9803–9817.

Woelk, H., & Schläfke, S. (2010). A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine, 17(2), 94–99.

Woolbright, B. L., & Jaeschke, H. (2017). Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure. Journal of Hepatology, 66(4), 836–848.

Xie, T., Song, S., Li, S., Ouyang, L., Xia, L., & Huang, J. (2015). Review of natural product databases. Cell Proliferation, 48(4), 398–404.

Younus, H. (2018). Therapeutic potentials of superoxide dismutase. International Journal of Health Sciences, 12(3), 88–93.

Zhang, C., Wang, N., Xu, Y., Tan, H.-Y., Li, S., & Feng, Y. (2018). Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study. International Journal of Molecular Sciences, 19(9), 2745.

Zhao, C., Sun, J., Fang, C., & Tang, F. (2014). 1,8-Cineol Attenuates LPS-Induced Acute Pulmonary Inflammation in Mice. Inflammation, 37(2), 566–572.

Ziaee, M., Khorrami, A., Ebrahimi, M., Nourafcan, H., Amiraslanzadeh, M., Rameshrad, M., Garjani, M., & Garjani, A. (2015). Cardioprotective Effects of Essential Oil of Lavandula angustifolia on Isoproterenol-induced Acute Myocardial Infarction in Rat. Iranian Journal of Pharmaceutical Research 14(1), 279–289.




How to Cite

CARDIA, G. F. E.; SILVA-COMAR , F. M. de S.; SILVA, E. L.; ROCHA, E. M. T. da; COMAR, J. F. .; SILVA-FILHO, S. E. .; ZAGOTTO, M.; UCHIDA, N. S.; BERSANI-AMADO, C. A.; CUMAN, R. K. N. Lavender (Lavandula officinalis) essential oil prevents acetaminophen-induced hepatotoxicity by decreasing oxidative stress and inflammatory response . Research, Society and Development, [S. l.], v. 10, n. 3, p. e43410313461, 2021. DOI: 10.33448/rsd-v10i3.13461. Disponível em: Acesso em: 17 apr. 2021.



Health Sciences