The beneficial effects of ozone therapy in acetaminophen-induced hepatotoxicity in mice

Pharmacol Rep. 2018 Apr;70(2):340-345. doi: 10.1016/j.pharep.2017.11.003. Epub 2017 Nov 13.


Background: The aim of the present study was to determine the therapeutic effects of medical ozone therapy on acute acetaminophen (APAP)-induced hepatotoxicity which were not clearly demonstrated in prior studies.

Method: Twenty-four mice were randomly assigned into three equal groups: Group 1 (control), Group 2 (APAP) and Group 3 (APAP +ozone). Hepatotoxicity was induced by APAP given as a single dose of 300mg/kg intraperitoneally in Groups 2 and 3. Additionally, Group 3 received 20mcg/0.5mL ozone intraperitoneal twice a day for the remaining of the study. Other groups received saline injections. On the fourth day of the study, biochemical variables (AST, ALT, ALP) and liver histopathology was assessed.

Results: Intraperitoneal administration of a single dose of APAP induced hepatocellular damage that was shown by both liver enzymes and histopathological changes (p<0.001). AST, ALT, ALP levels were elevated in both groups 2 and 3 and the difference from group 1 was statistically significant (p<0.01).Mean ALT and AST levels of group 2 were statistically significantly higher versus group 3 (p<0.01). In histopathological examinations; necrosis and inflammation were more prominent in Group 2 compared to Group 3 (p<0.01).

Conclusion: Ozone showed beneficial effects on APAP hepatotoxicity at a statistically significant level. It is known that ozone has therapeutic effects in various diseases owing to its antioxidant effects. The present study suggests that ozone may be utilized as a routine supplementary therapy in acute APAP hepatotoxicity.

Keywords: Acetaminophen; Hepatotoxicity; Ozone.

MeSH terms

  • Acetaminophen / pharmacology*
  • Alanine Transaminase / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Aspartate Aminotransferases / metabolism
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Glutathione / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Necrosis / drug therapy
  • Necrosis / metabolism
  • Necrosis / pathology
  • Ozone / pharmacology*


  • Antioxidants
  • Acetaminophen
  • Ozone
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione