Lotkova 2009 Acta Vet Brno

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Lotková H, Kučera O, Roušar T, Endlicher R, Křiváková P, Garnol T, Červinková Z (2009) Effect of S-adenosylmethionine on Acetaminophen-induced toxic injury of rat hepatocytes in vitro. Acta Vet Brno 78:603-13.

» doi:10.2754/avb200978040603 Open Access

Lotkova Halka, Kucera Otto, Rousar Tomas, Endlicher Rene, Stankova Pavla, Garnol T, Cervinkova Zuzana (2009) Acta Vet Brno

Abstract: Acetaminophen (AAP) overdose causes severe liver injury and is the leading cause of acute liver injury in humans. The mechanisms participating in its toxic effect are glutathione depletion, oxidative stress and mitochondrial dysfunction. S-adenosylmethionine (SAMe) is the principal biological methyl donor and is also a precursor of glutathione. In our previous studies we have documented a protective action of SAMe against various toxic injuries of rat hepatocytes in primary cultures. The aim of this study was to evaluate a possible protective effect of SAMe against AAP-induced toxic injury of primary rat hepatocytes. Hepatocytes were exposed to AAP (2.5 mM) or AAP together with SAMe at the final concentrations of 5, 25 or 50 mg/l for 24 h. Incubation of hepatocytes with AAP caused a significant increase of the leakage of lactate dehydrogenase (LDH) (p < 0.001) and decline of the activity of cellular dehydrogenases (WST- 1) (p < 0.001). Co-incubation of hepatocytes with SAMe at any dose did not improve these markers of cellular integrity. The functional indicators improved in hepatocytes co-cultured with SAMe - urea production was significantly increased when using the highest dose of SAMe (p < 0.05); albumin synthesis was higher in all cultured hepatocytes exposed to SAMe (p < 0.05). SAMe did not influence AAP-induced decrease of cellular content of glutathione. Mitochondrial respiration of harvested digitonin-permeabilized hepatocytes was measured; Complex II was more sensitive to toxic action of AAP, respiration was decreased by 20%. This decrease was completely abolished by SAMe.

Keywords: Hepatotoxicity, Hepatoprotective effect, Mitochondrial membrane potential, Urea, Albumin, Glutathione, LDH

O2k-Network Lab: CZ Hradec Kralove Cervinkova Z, CZ Pardubice Rousar T


Labels:

Stress:Oxidative stress;RONS  Organism: Rat  Tissue;cell: Liver  Preparation: Permeabilized cells  Enzyme: Complex II;succinate dehydrogenase 


Pathway:HRR: Oxygraph-2k