Effects of hyperbaric oxygen therapy on acetaminophen induced nephrotoxicity and hepatotoxicity: the role of heme oxygenase-1

  • İclal Karatop-Cesur Department of Undersea and Hyperbaric Medicine, Gülhane Military Medical Academy, Etlik, Ankara, Turkey
  • Senol Yildiz Department of Undersea and Hyperbaric Medicine, Gülhane Military Medical Academy, Etlik, Ankara, Turkey
  • Günalp Uzun Department of Undersea and Hyperbaric Medicine, Gülhane Military Medical Academy, Etlik, Ankara, Turkey https://orcid.org/0000-0002-8717-6230
  • Yeşim Öztaş Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey
  • Suna Sabuncuoglu Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
  • Yasin Ilgaz Department of Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
  • Ayhan Kutlu Department of Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
  • Eyup Dogan Department of Medical Microbiology, Gülhane Military Medical Academy, Etlik, Ankara, Turkey
  • Emin Oztas Department of Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
Keywords: Paracetamol, hyperbaric oxygen, kidney, liver, heme oxygenase-1

Abstract

The aim of this study was to investigate the effects of hyperbaric oxygen (HBO) therapy on acetaminophen (APAP) induced renal and liver injudr and the role of heme oxygenase-1 (HO-1) activation. Wistar-Albino rats were randomly assigned into four groups. Control group received no treatment. APAP (3gr/kg) was administered by gastric lavage in APAP group. Animals in the APAP+HBO and APAP+zinc protoporphyrin (ZnPP)+HBO groups received HBO therapy (90 min at 2.5 atm), starting 1 hour after APAP administration, for 2 consecutive days.HO-1 activity was inhibited by ZnPP. APAP+ZnPP+HBO group received intraperitoneal 50 µmol\kg ZnPP injection 30 minutes after APAP treatment and HBO therapy for 2 days. Serum and tissue samples were taken at 48 hours after APAP treatment. Renal and liver functions were evaluated by serum levels of urea, creatinine and transaminases. Lipid  peroxidation and tissue levels of antioxidant enzymes were measure by ELISA. Tissue injury was evaluated by light microscopy.HO-1 level was determined by immunohistochemistry. HO-1 mRNA level was investigated by polymerase chain reaction (PCR). Serum transaminase levels significantly increased after APAP treatment (p<0.05) and severe tissue injury was detected on liver slides (p<0.05). HBO therapy both reduced transminase levels and alleviated liver injury (p<0.05). The inhibition of HO-1 by ZnPP agreviated liver injury (p<0.05). HBO therapy reduced lipid peroxidation (p<0.05) and increased the activity of superoxide dismutase (p<0.05). Tissue HO-1 level increased after APAP treatment (p<0.05). HBO therapy significantly increased HO-1 level (p<0.05). APAP nephrotoxicity was not observed in this model. In conclusion, HBO therapy ameliorates APAP induced liver injury by increasing liver HO-1 levels.

Author Biographies

İclal Karatop-Cesur, Department of Undersea and Hyperbaric Medicine, Gülhane Military Medical Academy, Etlik, Ankara, Turkey

Department of Undersea and Hyperbaric Medicine, Gülhane Military Medical Academy, Etlik, Ankara, Turkey

Senol Yildiz, Department of Undersea and Hyperbaric Medicine, Gülhane Military Medical Academy, Etlik, Ankara, Turkey

Department of Undersea and Hyperbaric Medicine, Gülhane Military Medical Academy, Etlik, Ankara, Turkey

Günalp Uzun, Department of Undersea and Hyperbaric Medicine, Gülhane Military Medical Academy, Etlik, Ankara, Turkey

Department of Undersea and Hyperbaric Medicine, Gülhane Military Medical Academy, Etlik, Ankara, Turkey

Yeşim Öztaş, Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Suna Sabuncuoglu, Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

Yasin Ilgaz, Department of Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey

Department of Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey

Ayhan Kutlu, Department of Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey

Department of Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey

Eyup Dogan, Department of Medical Microbiology, Gülhane Military Medical Academy, Etlik, Ankara, Turkey

Department of Medical Microbiology, Gülhane Military Medical Academy, Etlik, Ankara, Turkey

Emin Oztas, Department of Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey

Department of Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey

APAP treatment, liver injury, hyperbaric oxygen, heme oxygenate-1
Published
2016-09-30
How to Cite
Karatop-Cesur, İclal, Yildiz, S., Uzun, G., Öztaş, Y., Sabuncuoglu, S., Ilgaz, Y., Kutlu, A., Dogan, E., & Oztas, E. (2016). Effects of hyperbaric oxygen therapy on acetaminophen induced nephrotoxicity and hepatotoxicity: the role of heme oxygenase-1. Disease and Molecular Medicine, 4(3), 37-42. https://doi.org/10.5455/dmm.20160802110754
Section
Original Article

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