Curcumin prevents paracetamol-induced liver mitochondrial alterations

被引:23
作者
Fernando Granados-Castro, Luis [1 ]
Sarai Rodriguez-Rangel, Daniela [1 ]
Fernandez-Rojas, Berenice [1 ]
Carlos Leon-Contreras, Juan [2 ]
Hernandez-Pando, Rogelio [2 ]
Noel Medina-Campos, Omar [1 ]
Eugenio-Perez, Dianelena [1 ]
Pinzon, Enrique [3 ]
Pedraza-Chaverri, Jose [1 ]
机构
[1] Univ Nacl Autonoma Mexico, Fac Chem, Dept Biol, Lab 209,Bldg F, Univ City 04510, DF, Mexico
[2] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Expt Pathol Sect, Mexico City, DF, Mexico
[3] Univ Nacl Autonoma Mexico, Fac Med, Anim Care Unit, Univ City 04510, DF, Mexico
关键词
aconitase; adenosine triphosphate synthesis; mitochondrial dysfunction; mitochondrial membrane potential; respiratory complexes; OXIDATIVE STRESS; INDUCED HEPATOTOXICITY; OXYGEN-CONSUMPTION; ACETAMINOPHEN; PROTECTS; RESPIRATION; INHIBITION; ACONITASE; DAMAGE;
D O I
10.1111/jphp.12501
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
ObjectiveIn the present study was evaluated if curcumin is able to attenuate paracetamol (PCM)-induced mitochondrial alterations in liver of mice. MethodsMice (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 findingsCurcumin 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. ConclusionsThese results indicate that the protective effect of curcumin in PCM-induced hepatotoxicity is associated with attenuation of mitochondrial dysfunction.
引用
收藏
页码:245 / 256
页数:12
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