Comparative Clinical Pathology

, Volume 27, Issue 5, pp 1367–1374 | Cite as

Protection of CCl4-induced hepatotoxicity by Trachyspermum ammi essential oil in mice

  • Mohammad Mahdi ZangenehEmail author
  • Mohammad Hosein Farzaei
  • Nader Goodarzi
  • Akram Zangeneh
Original Article


Ethnomedicinal plants are considered as new resources for producing agents that could act as alternatives to chemical drugs. Trachyspermum ammi (Ta) has been used in medicine as an antioxidant, anti-inflammatory, antiparasitical, antiviral, antifungal, and antibacterial agent. The aim of the present study was to investigate the protective effect of Ta essential oil against CCl4-induced hepatotoxicity in mice. Thirty-five mice were divided into five groups (n = 7). Group I served as negative control, received 1 mL/kg olive oil intraperitoneally and 0.5 mL distilled water through gavage. Group II served as positive control, received 1 mg/kg CCl4 mixed with olive oil in the ratio of 5:5, intraperitoneally, and 0.5 mL distilled water orally. Groups III, IV, and V received CCl4mixed with olive oil in the ratio of 5:5 intraperitoneally and 200, 800, and 1600 μg/kg of Ta essential oil through gavage for 45 consecutive days. The results showed that thymol (44.2%), p-cymene (25.7%), and γ-terpinene (25.1%) are the main components of Ta essential oil. Different doses of Ta essential oil could significantly (p < 0.05) decreased the raised levels of alkaline phosphatase and alanine aminotransferase toward control levels. The volume and weight of the liver, and volume of hepatocytes and sinusoids which were increased significantly (p < 0.05) in positive control group compared to the negative control group, were significantly decreased with high dose of Ta essential oil (1600 μg/kg) (p < 0.05). The volume of central veins, portal veins, hepatic arteries, and bile ducts did not have significant changes (p < 0.05). In conclusion, Ta essential oil can protect hepatic tissue and regulate liver enzymes in CCl4-induced hepatotoxicity due to its antioxidant compounds.


Trachyspermum ammi Hepatotoxicity CCl4 Essential oil 



The authors would like to thank Mr. Moradi and Dr. Massomi for their technical assistances.

Authors’ contributions

MHF prepared the plant essential oil. MMZ performed biochemical assessments and contributed in the statistical analysis. NG performed the stereological plan and wrote the manuscript. AZ was involved in animal handling and treatment.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the ethics committee of Kermanshah University of Medical Sciences (KUMS.REC.1395.497).


  1. Ali S, Al-Amin T, Mohamed A, Gameel A (2009) Hepatoprotective activity of aqueous and methanolic extracts of Capparis decidua stems against carbon tetrachloride induced liver damage in rats. J Pharm Toxicol 4(4):167–172CrossRefGoogle Scholar
  2. Alia M, Horcajo C, Bravo L, Goya L (2003) Effect of grape antioxidant dietary fiber on the total antioxidant capacity and the activity of liver antioxidant enzymes in rats. Nutr Res 23(9):1251–1267CrossRefGoogle Scholar
  3. Bairwa R, Sodha RS, Rajawat BS (2012) Trachyspermum ammi. Pharmacogn Rev 6(11):56–60CrossRefPubMedPubMedCentralGoogle Scholar
  4. Faramarzi E, Zangeneh MM, Zangeneh A, Moradi R (2017) Effect of Cinnamomum zelanicumon oil on hyponeophagia anxiety test in Balb C male mice. Onl J Vet Res 21(2):77–80Google Scholar
  5. Foroughi A, Zangeneh MM, Kazemi N, Zangeneh A (2016a) An in vitro study on antimicrobial properties of Allium noeanumreut ex regel: an ethnomedicinal plant. Iranian J Publ Health 45(2):32Google Scholar
  6. Foroughi A, Pournaghi P, Najafi F, Zangeneh A, Zangeneh MM, Moradi R (2016b) Antibacterial effect and phytochemical screening of essential oil of Pimpinella anisum against Escherichia coli O157:H7 and Staphylococcus aureus. Int J Current Med Pharm Res 7(6):367–371Google Scholar
  7. Foroughi A, Pournaghi P, Najafi F, Zangeneh A, Zangeneh MM, Moradi R (2017) Medicinal plants: antibacterial effects and chemical composition of essential oil of Foeniculum vulgare. IJCPR 8(1):13–17CrossRefGoogle Scholar
  8. Ghashghaii A, Hashemnia M, Nikousefat Z, Zangeneh MM, Zangeneh A (2017) Wound healing potential of methanolic extract of Scrophularia striata in rats. Pharm Sci 23(4):256–263CrossRefGoogle Scholar
  9. Goodarzi N, Zangeneh MM, Zangeneh A, Najafi F, Tahvilian R (2017) Protective effects of ethanolic extract of Allium Saralicum R.M. Fritsch on CCl4-induced hepatotoxicity in mice. J Rafsanjan Univ Med Sci 16(3):227–238Google Scholar
  10. Goodarzi N, Doorgard E, Pournaghi P (2018) The ameliorative potential of Sophora alopecuroides essential oil on CCl4-induced hepatotoxicity in mice; a stereological study. Res J Pharmacogn 5(1):47–54Google Scholar
  11. Goorani S, Zangeneh MM, Zangeneh A, Poorshamohammad C, Abiari M, Moradi R, Najafi F, Tahvilian R (2018) Study of wound healing potential of Stevia rebaudiana ethanol extract in male rats. Res J Pharmacogn 5(1):23–30Google Scholar
  12. Hagh-Nazari L, Goodarzi N, Zangeneh MM, Zangeneh A, Tahvilin R, Moradi R (2017) Stereological study of kidney in streptozotocin-induced diabetic mice treated with ethanolic extract of Stevia rebaudiana (bitter fraction). Comp Clin Pathol 26(2):455–463CrossRefGoogle Scholar
  13. Halliwell B, Gutteridge J (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219(1):1–14CrossRefPubMedPubMedCentralGoogle Scholar
  14. Jia HL, Ji QL, Xing SL, Zhang PH, Zhu GL, Wang XH (2010) Chemical composition and antioxidant, antimicrobial activities of the essential oils of Thymus marschallianus Will. and Thymus proximus Serg. J Food Sci 75(1):59–65CrossRefGoogle Scholar
  15. Jordan MJ, Sanchez-Gomez P, Jimenez JF, Quilez M, Sotomayor JA (2010) Chemical composition and antiradical activity of the essential oil from Satureja intricata, S. obovata; and their hybrid Datureja x delpozoi. Nat Prod Commun 5:629–634PubMedGoogle Scholar
  16. Loguercio C, Federico A (2003) Oxidative stress in viral and alcoholic hepatitis. Free Radic Biol Med 34(1):1–10CrossRefPubMedGoogle Scholar
  17. Mandarim-de-Lacerda CA (2003) Stereological tools in biomedical research. An Acad Bras Cienc 5(4):469–486CrossRefGoogle Scholar
  18. Manjunatha BK, Vidya SM (2008) Hepatoprotective activity of Vitex trifolia against carbon tetrachloride-induced hepatic damage. Ind J Pharm Sci 70(2):241–245CrossRefGoogle Scholar
  19. Moradi R, Hajialiani M, Zangeneh MM, Zangeneh A, Tahvilian R, Hidaryan H, Rezaeeas N, Kohneshin A (2017a) Antibacterial properties of an Iranian ethnomedicinal plant. Int J Ayu Pharm Chem 6(3):128–137Google Scholar
  20. Moradi RM, Hajialiani M, Zangeneh MM, Zangeneh A, Faizi S, Zoalfaghari M, Marabi A (2017b) Study a plant extract as an antibacterial agent. Int J Current Med Pharm Res 3(2):1360–1362Google Scholar
  21. Najafi F, Tahvilian R, Zangeneh MM, Zangeneh A, Moradi R (2016) Screening of essential oil of Allium sativum for antibacterial effects against Bacillus subtilis. IJRSR 7(11):14172–14176Google Scholar
  22. Najafi F, Goodarzi N, Zangeneh MM, Zangeneh A, Hagh-Nazari L (2017) Antidiabtic and hepatoprotective effects of bitter fraction of Stevia rebaudiana alcoholic extract on streptozotocin-induced diabetic male mice. J Rafsanjan Univ Med Sci 16(6):493–504Google Scholar
  23. Nyengaard JR (1999) Stereologic methods and their application in kidney research. J Am Soc Nephrol 10(5):1100–1123PubMedGoogle Scholar
  24. Park EG, Jeon CH, Ko G, Kim J, Sohn DH (2000) Protective effect of curcumin in rat liver injury induced by carbon tetrachloride. J Pharm Pharmacol 52(4):437–440CrossRefPubMedGoogle Scholar
  25. Poorshamohammad C, Souri N, Amini Z, Kosari F, Jamshidpour R, Zangeneh MM, Zangeneh A (2017) Cucurbita moschata: a plant with antibacterial properties. Int J Current Med Pharm Res 3(2):1356–1359Google Scholar
  26. Recknagel RO, GlendeJr EA, Dolak JA, Waller RL (1989) Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther 43(1):139–154CrossRefPubMedGoogle Scholar
  27. Recknagel RO, GlendeJr EA, Britton RS (1991) Free radical damage and lipid peroxidation. In: Meeks RG (ed) Hepatotoxicology. CRC Press, Florida, pp 401–436Google Scholar
  28. Roy A, Bhoumik D, Sahu RK, Dwivedi J (2014) Medicinal plants used in liver protection—a review. UK J Pharm Biosci 2(1):23–33CrossRefGoogle Scholar
  29. Sahreen S, Khan MR, Khan RA (2011) Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat. BMC Complement Altern Med 11(1):48CrossRefPubMedPubMedCentralGoogle Scholar
  30. Tahvilian R, Moradi R, Hajialiani M, Zangeneh MM, Zangeneh A, Yazdani H, Zhale H (2016) Chemical composition and screening of antibacterial activities of essential oil of Pistacia khinjuk against Bacillus subtilis (ATCC No. 21332). Int J Current Med Pharm Res 2(12):1098–1102Google Scholar
  31. Tahvilian R, Moradi R, Hajialiani M, Zangeneh MM, Zangeneh A, Yazdani H, Zhaleh H (2017a) Evaluation of antibacterial properties of essential oil of Pistacia khinjuk. Int J Res Pharm Sci 7(1):1–6Google Scholar
  32. Tahvilian R, Moradi R, Zhaleh H, Zangeneh MM, Zangeneh A, Yazdani H, Hajialiani M (2017b) Chemical composition and screening of antibacterial activity of essential oil of Pistacia khinjuk against two selected pathogenic bacteria. Ann Trop Med Public Health 10(5):1159–1164CrossRefGoogle Scholar
  33. Viuda-Martos M, Navajas YR, Zapata ES, Fernández-López J, Pérez-Alvarez JA (2010) Antioxidant activity of essential oils of five spice plants widely used in a Mediterranean diet. Flavour Fragr J 25(1):13–19CrossRefGoogle Scholar
  34. Weber LWD, Boll M, Stampfl A (2003) Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol 33(2):105–136CrossRefPubMedGoogle Scholar
  35. Woods L, Ingelfinder J, Nyengaard J, Rasch R (2001) Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res 49(4):460–467CrossRefPubMedGoogle Scholar
  36. Yang SA, Jeon SK, Lee EJ, Shim EH, Lee IS (2010) Comparative study of the chemical composition and antioxidant activity of six essential oils and their components. Nat Prod Res 24(2):140–151CrossRefPubMedGoogle Scholar
  37. Zangar RC, Benson JM, Burnett VL, Springer DL (2000) Cytochrome P4502E1 is the primary enzyme responsible for low-dose carbon tetrachloride metabolism in human liver microsomes. Chem Biol Interact 125:233–243CrossRefPubMedGoogle Scholar
  38. Zangeneh MM, Najafi F, Tahvilian R, Zangeneh A, Souri N, Zarei MS, Khedri MR, Bahrami E, Shamohammadi M (2016) Ethnomedicinal plant: antibacterial effects of essential oil of Allium sativum against Pseudomonas aeruginosa (PTCC No. 1707) in west of Iran. IJRSR 7(11):14243–14247Google Scholar
  39. Zangeneh MM, Tahvilian R, Zangeneh A, Moradi R, Najafi F, Haghnazari L (2017a) Effect of Alhagi maurorum oil on anxiety markers in Balb/C male mice. Onl J Vet Res 21(3):115–117Google Scholar
  40. Zangeneh MM, Zangeneh A, Tahvilian R, Moradi R, Kiani K, Khalili M, Shikhi T, Amiri A (2017b) Ethnomedicinal plants: evaluation of in vitro antibacterial properties of Verbascum thapsus against Bacillus subtilis ATCC No. 21332. Int J Ayu Pharm Chem 6(3):155–166Google Scholar
  41. Zangeneh MM, Goodarzi N, Zangeneh A, Najafi F, Tahvilian R (2018) Hypoglycemic, nephroprotective effects of aqueous extract of Stevia rebaudiana (sweet fraction) in streptozotocin-induced diabetic mice. J Ardabil Univ Med Sci 17(4):437–446Google Scholar
  42. Zekrizadeh Z, Farokhy F (2014) The effect of hydroalcoholic extract of ginger (HEG) on histological and biochemical parameters of kidney in epileptic rats treated with lamotrigine. Qom Univ Med Sci J 8(5):54–62Google Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical Science, Faculty of Veterinary MedicineRazi UniversityKermanshahIran
  2. 2.Pharmaceutical Sciences Research Center, Faculty of PharmacyKermanshah University of Medical SciencesKermanshahIran
  3. 3.Department of Basic Science, Faculty of Veterinary MedicineRazi UniversityKermanshahIran

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