Anat Cell Biol.  2019 Sep;52(3):302-311. 10.5115/acb.18.180.

Improvement in histology, enzymatic activity, and redox state of the liver following administration of Cinnamomum zeylanicum bark oil in rats with established hepatotoxicity

  • 1Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
  • 2Department of Anatomical Sciences, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
  • 3Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
  • 4Department of Pharmacognosy, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.


Formaldehyde (FA) is an environmentally-available pollutant. Since the liver acts as a detoxifier in the human body, it is the first and most affected organ in individuals exposed to higher-than-normal amounts of FA. FA mainly alters oxidant/antioxidant status and initiates oxidative stress, and by means, causes functional damage to the liver. Thus, it is important to identify natural bioactive compounds with antioxidant properties in order to be used as food additives. Cinnamon (Cinnamomum zeylanicum) is a popular flavor and also a medicinal plant with a variety of beneficial effects. In the present original study, cinnamon essential oil (CEO) has been administrated at doses of 10, 20, and 100 mg/kg, orally, to hepatotoxicity rat models caused by FA (10 mg/kg, intraperitoneally). Liver enzymes and its histology were assessed and oxidative stress biomarkers in the liver tissue were also examined. CEO administration caused a significant increase in superoxide dismutase, glutathione peroxidase, and catalase and a prominent decrease in nitric oxide levels in the liver tissue. Also, in serum samples, CEO significantly reduced the elevated amounts of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. When assessed histologically, portal area and central vein fibrosis alongside with the hepatocytes' hypereosinophilia and swelling, focal inflammation, and necrotic areas were found to be prominently decreased in the CEO group. In conclusion, our study suggested that the CEO may have the potential for being used against FA-induced hepatotoxicity.


Formaldehyde; Oxidative stress; Liver; Cinnamomum zeylanicum; Antioxidants

MeSH Terms

Alanine Transaminase
Alkaline Phosphatase
Aspartate Aminotransferases
Cinnamomum zeylanicum*
Food Additives
Glutathione Peroxidase
Human Body
Models, Animal
Nitric Oxide
Oxidative Stress
Plants, Medicinal
Superoxide Dismutase
Alanine Transaminase
Alkaline Phosphatase
Aspartate Aminotransferases
Food Additives
Glutathione Peroxidase
Nitric Oxide
Superoxide Dismutase


  • Fig. 1 The effect of cinnamon essential oil administration on liver enzymes in serum among groups. FA treatment significantly increased the serum levels of ALT (A), AST (B), and ALP (C) as a sign of tissue damage. CEO administration caused an increase in serum levels of all three liver hormones, indicating the protection CEO administration caused against FA-induced hepatotoxicity. C, control; FA, formaldehyde 10 mg/kg; V, FA 10 mg/kg+solvent; CEO10,20,100, FA 10 mg/kg+cinnamon essential oil 10,20,100 mg/kg; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase. ****P<0.0001.

  • Fig. 2 Effect of cinnamon essential oil administration on oxidative stress markers in liver among groups. Levels of SOD (A), GPx (C), and CAT (D) were found to be decreased due to FA treatment, as a result of oxidative stress. CEO administration at the dose of 100 mg/kg ameliorated these abnormal elevations. MDA (B) and NO (E) activities which were increased in response to FA treatment, were significantly decreased following 100 mg/kg CEO administration. C, control; FA, formaldehyde 10 mg/kg; V, FA 10 mg/kg+solvent; CEO10,20,100, FA 10 mg/kg+cinnamon essential oil 10,20,100 mg/kg; SOD, superoxide dismutase; GPx, glutathione peroxidase; CAT, catalase; MDA, malondialdehyde; NO, nitric oxide. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

  • Fig. 3 Histological alterations of liver following formaldehyde (FA) administration in comparison with control in H&E stained sections (×200). Samples from FA group (B, D) showed an increase in hyper-eosinophilic and swelled hepatocytes (arrowheads), focal inflammation (arrows) and necrotic areas (asterisk) when compared to control group (A, C). This shows how FA caused damage to the cellular architecture of portal area and liver parenchyma. PV, portal vein; HA, hepatic artery; BD, bile duct.

  • Fig. 4 Histological alterations and fibrotic changes of liver following co-treatment of formaldehyde (FA) and cinnamon essential oil (CEO; 100 mg/kg) in H&E and Masson's trichrome stained sections (×200). CEO administration ameliorated FA-induced hepatocytes hyper-eosinophilia and swelling (arrowheads), inflammation (arrows), and necrosis (not seen in the picture) in H&E stained sections (A, C). It also inhibited fibrous tissue formation around portal area and central vein in Masson's trichrome stained sections (B, D). PV, portal vein; HA, hepatic artery; BD, bile duct; CV, central vein.

  • Fig. 5 Fibrotic changes of liver following formaldehyde (FA) administration in comparison with control in Masson's trichrome stained sections (×200). Samples from FA group (B, D) showed an increase in fibrous tissue around portal area and central vein (arrowheads) when compared with control group (A, C). This figure shows that FA prominently disrupts portal area network by causing fibrotic tissue. PV, portal vein; HA, hepatic artery; BD, bile duct; CV, central vein.


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