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