Curcumin prevents paracetamol-induced liver mitochondrial alterations

Objective In the present study was evaluated if curcumin is able to attenuate paracetamol (PCM)‐induced mitochondrial alterations in liver of mice. Methods Mice (n = 5–6/group) received curcumin (35, 50 or 100 mg/kg bw) 90 min before PCM injection (350 mg/kg bw). Plasma activity of alanine aminotran...

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Veröffentlicht in:Journal of pharmacy and pharmacology 2016-02, Vol.68 (2), p.245-256
Hauptverfasser: Granados-Castro, Luis Fernando, Rodríguez-Rangel, Daniela Sarai, Fernández-Rojas, Berenice, León-Contreras, Juan Carlos, Hernández-Pando, Rogelio, Medina-Campos, Omar Noel, Eugenio-Pérez, Dianelena, Pinzón, Enrique, Pedraza-Chaverri, José
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Sprache:eng
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Zusammenfassung:Objective In the present study was evaluated if curcumin is able to attenuate paracetamol (PCM)‐induced mitochondrial alterations in liver of mice. Methods Mice (n = 5–6/group) received curcumin (35, 50 or 100 mg/kg bw) 90 min before PCM injection (350 mg/kg bw). Plasma activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was measured; histological analyses were done; and measurement of mitochondrial oxygen consumption, mitochondrial membrane potential, ATP synthesis, aconitase activity and activity of respiratory complexes was carried out. Key findings Curcumin prevented in a dose‐dependent manner PCM‐induced liver damage. Curcumin (100 mg/kg) attenuated PCM‐induced liver histological damage (damaged hepatocytes from 28.3 ± 7.7 to 8.3 ± 0.7%) and increment in plasma ALT (from 2300 ± 150 to 690 ± 28 U/l) and AST (from 1603 ± 43 to 379 ± 22 U/l) activity. Moreover, curcumin attenuated the decrease in oxygen consumption using either succinate or malate/glutamate as substrates (evaluated by state 3, respiratory control ratio, uncoupled respiration and adenosine diphosphate/oxygen ratio), in membrane potential, in ATP synthesis, in aconitase activity and in the activity of respiratory complexes I, III and IV. Conclusions These results indicate that the protective effect of curcumin in PCM‐induced hepatotoxicity is associated with attenuation of mitochondrial dysfunction.
ISSN:0022-3573
2042-7158
DOI:10.1111/jphp.12501