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2018 ; 4
(2
): e00521
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Ethyl pyruvate attenuates acetaminophen-induced liver injury and prevents
cellular injury induced by N-acetyl-p-benzoquinone imine
#MMPMID29560444
Nagatome M
; Kondo Y
; Kadowaki D
; Saishyo Y
; Irikura M
; Irie T
; Ishitsuka Y
Heliyon
2018[Feb]; 4
(2
): e00521
PMID29560444
show ga
Acetaminophen, a common analgesic/antipyretic, is a frequent cause of acute liver
failure in Western countries. The development of an effective cure against
acetaminophen hepatotoxicity is crucial. Ethyl pyruvate, an ethyl ester
derivative of pyruvic acid, has been identified as a possible candidate against
acetaminophen hepatotoxicity in animal experiments. However, the mode of the
hepatoprotective action of ethyl pyruvate remains unclear. We examined the
hepatoprotective effect of ethyl pyruvate against hepatocyte injury and oxidative
stress in a mouse model of acetaminophen hepatotoxicity. In addition, to examine
whether ethyl pyruvate has direct hepatocellular protection against acetaminophen
hepatotoxicity to counteract the influence of inflammatory cells, such as
macrophages, we examined the effects of ethyl pyruvate on cellular injury induced
by N-acetyl-p-benzoquinone imine, a toxic metabolite of acetaminophen, in a human
hepatocyte cell line, HepG2 cells. Treatment with ethyl pyruvate significantly
prevented increases in serum transaminase levels and hepatic centrilobular
necrosis induced with an acetaminophen overdose in mice in a dose-dependent
manner. Although hepatic DNA fragmentation induced by acetaminophen was also
attenuated with ethyl pyruvate, nitrotyrosine formation was not inhibited. Ehyl
pyruvate significantly attenuated mitochondria dehydrogenase inactivity induced
by N-acetyl-p-benzoquinone imine in HepG2 cells. The attenuating effect was also
observed in a rat hepatocyte cell line. Increases in annexin V and propidium
iodide-stained cells induced by N-acetyl-p-benzoquinone imine were prevented with
ethyl pyruvate in HepG2 cells. Pyruvic acid, a parent compound of ethyl pyruvate,
tended to attenuate these changes. The results indicate that ethyl pyruvate has
direct hepatocellular protection against N-acetyl-p-benzoquinone imine induced
injury observed in acetaminophen overdose. The in vivo and in vitro results
suggest that ethyl pyruvate attenuates acetaminophen-induced liver injury via, at
least in part, its cellular protective potential.