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. 2016 Oct 28;11(10):e0165638. doi: 10.1371/journal.pone.0165638

Fig 2. Activation of AMPK prevented drugs-induced mitochondrial dysfunction.

Fig 2

Rat or human hepatocytes were treated with acetaminophen (APAP) or diclofenac (Diclo) in the presence or the absence of AMPK activator AICAR (200μM). Cellular ATP levels were measured using ATP determination kit (Invitrogen). Percentages relative to respective controls were calculated. (A) AICAR prevented the decrease in cellular ATP in rat hepatocytes treated with acetaminophen (10mM, 24h) or diclofenac (250μM, 24h). Treatment with AICAR alone significantly increased ATP level. The relative ATP were 61% in APAP; 100% in APAP + AICAR; 65% in Diclo; 104% in Diclo + AICAR and 130% in AICAR, and (B) AICAR prevented the decrease in ATP in human hepatocytes treated with acetaminophen (25mM, 24h) or diclofenac (1000μM, 24h). The relative ATP levels were 28% in APAP; 92% in APAP + AICAR; 59% in Diclo; 100% in Diclo + AICAR and 147% in AICAR. Treatment with AICAR alone significantly increased ATP level. (C) Mitochondrial potentials were measured and quantitatively analysed using Image J (see details in Methods). Percentages relative to respective controls were calculated. AICAR prevented the decrease in mitochondrial potential in rat hepatocytes treated with acetaminophen (10mM, 24h) or diclofenac (250μM, 24h). Treatment with AICAR alone significantly increased mitochondrial potential. FCCP treatment was used as negative control. The relative mitochondrial potentials were 62% in APAP; 96% in APAP + AICAR; 72% in Diclo; 97% in Diclo + AICAR; 113% in AICAR and 27% in FCCP. (D) AICAR also prevented the decreases of mitochondrial potential in human hepatocytes treated with acetaminophen (25mM, 24h) or diclofenac (1000μM, 24h). The relative mitochondrial potentials were 68% in APAP; 96% in APAP + AICAR; 44% in Diclo; 91% in Diclo + AICAR; 136% in AICAR and 30% in FCCP (* p<0.05, ** p<0.01 and *** p<0.001).