doiSerbia

The effects of ethanol on paracetamol-induced oxidative stress in mice liver

Mladenović Dušan (Faculty of Medicine, Department of Pathophysiology, Belgrade)
Ninković Milica (Institute for Medical Research, Millitary Medical Academy, Belgrade)
Vučević Danijela (Faculty of Medicine, Department of Pathophysiology, Belgrade)
Čolić Miodrag (Institute for Medical Research, Millitary Medical Academy, Belgrade)
Micev Marjan (Institute for Digestive Diseases, Clinical Centre of Serbia, Belgrade)
Todorović Vera (Faculty of Stomatology Pančevo, University of Academy Trade, Novi Sad)
Stanković Milena (Faculty of Medicine, Department of Pathophysiology, Belgrade)
Radosavljević Tatjana (Faculty of Medicine, Department of Pathophysiology, Belgrade)

The aim of our study was to investigate the effects of binge drinking on paracetamol induced oxidative stress in mice liver. Male Swiss mice were divided into groups: control; ethanol-treated group (E) in five subsequent doses of 2 g/kg by orogastric tube; paracetamol-treated group (P) in a dose of 300 mg/kg intraperitoneally; group that received paracetamol 12 hrs after the last dose of ethanol (PE). Blood and liver samples were collected for determination of oxidative stress parameters 6, 24 and 48 hrs after treatment. Prior binge drinking potentiated paracetamol-induced rise in liver malondialdehyde level 48 hours after treatment in comparison with P and E groups (17.14 ± 1.98 vs 13.14 ± 0.82 and 12.99 ± 1.18 μmol/L, p<0.01). Ethanol and paracetamol in combination induced a more pronounced decrease in liver GSH level than either of these substances alone at all time intervals (p<0.01). Total liver superoxide dismutase (SOD) activity was significantly lower in PE 48 hours after treatment in comparison with P and E groups (251.73 ± 80.63 vs 707.62 ± 179.92 and 1179.62 ± 147.94 U/mg prot., p<0.01). The lowest MnSOD activity in PE group was detected 48 hrs after treatment (86.52 ± 28.31; 41.13 ± 11.07 and 23.16 ± 5.18 U/mg prot. in P, E and PE groups, p<0.05, respectively). Prior binge ethanol drinking potentiates paracetamol-induced reduction of antioxidative capacity of hepatocytes due to GSH depletion and SOD activity reduction, simultaneously increasing lipid peroxidation caused by paracetamol.

Keywords: ethanol, paracetamol, oxidative stress, liver, mice

Projekat Ministarstva nauke Republike Srbije, br. 175015