Activation of mitogen activated protein kinase (MAPK) during d-galactosamine intoxication in the rat liver

Nishioka, Hitomi; Kishioka, Terumi; Iida, Chinatsu; Fujii, Kozue; Ichi, Ikuyo; Kojo, Shosuke

doi:10.1016/j.bmcl.2006.02.057

Cited by 18 publications

(17 citation statements)

References 27 publications

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“…These results indicated that oxidative stress and the activation of JNK and ERK took place almost simultaneously, as previously reported (9). This result also indicated that oxidative stress and the activation of these MAPKs took place without delay if the former caused the latter as generally assumed.…”

Section: Discussionsupporting

confidence: 89%

“…Phosphorylated JNK at 54 kDa and phospho-ERK significantly increased transiently 6-12 h after treatment with D-Galn, when the liver vitamin C decreased as in a previous study (9). These results indicated that oxidative stress and the activation of JNK and ERK took place almost simultaneously, as previously reported (9).…”

Section: Discussionsupporting

confidence: 87%

“…Phosphorylated p38 MAPK was not significantly changed by administration of D-Galn (300 mg/kg, this study), while it was increased by D-Galn at a dose of 1 g/ kg (9), where DMSO did not show an appreciable protective effect (data not shown). This may be due to the decrease in the dose of D-Galn.…”

Section: Discussionmentioning

confidence: 54%

“…Determination was made as previously described ( 9 ). Homogenization was done basically as reported ( 12 ).…”

Section: Methodsmentioning

confidence: 99%

“…In this report, we have attempted to investigate whether DMSO functions in vivo as an antioxidant and protects against necrosis of the liver caused by D -Galn even in a pharmacological dose. For this purpose we evaluated oxidative stress using hepatic vitamin C level and activation profiles of the three major subclasses of the MAPK (mitogen activated protein kinase) family, namely, JNK (c-Jun NH 2 -terminal kinase), p38 MAPK, and ERK (extracellular signal-related kinase), which were activated by a high dose of D -Galn intoxication ( 9 ).…”

mentioning

confidence: 99%

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Inhibitory Effect of Dimethyl Sulfoxide (DMSO) on Necrosis and Oxidative Stress Caused by D-Galactosamine in the Rat Liver

Iida

Fujii

Koga

et al. 2007

J Nutr Sci Vitaminol

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Summary D -Galactosamine ( D -Galn: 300 mg/kg) was intraperitoneally administered to rats. After 6 h the activity of plasma GOT and GPT was significantly higher than that of the control group and plasma GOT and GPT activities increased thereafter. These results indicated that the necrotic process was initiated at about 6 h and developed thereafter. With coadministration of DMSO (1 h before administration of D -Galn: 2.5 mL/kg, oral), plasma GOT and GPT were significantly lower, showing that DMSO inhibited the necrotic action of DGaln. After 6-24 h of D -Galn administration, the hepatic level of vitamin C, the most sensitive indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced 6 h after D -Galn intoxication and thereafter. DMSO significantly restored the liver vitamin C level 24 h after D -Galn injection, demonstrating that DMSO effectively ameliorated the oxidative stress caused by D -Galn, resulting in the prevention of necrosis of the liver. Phosphorylated JNK and phospho-ERK were significantly increased transiently 6-12 h after treatment with D -Galn. These results indicated that oxidative stress and the activation of JNK took place almost simultaneously. Phosphorylated p38 MAPK was not changed and DMSO treatment did not affect the change of these MAPKs by D -Galn. Key Words DMSO, galactosamine, MAPK, oxidative stress, vitamin C Hepatoprotection remains one of the major challenges in nutritional and clinical therapy to limit liver injuries such as chronic hepatitis and fulminant hepatic failure. To study this issue more effectively, experimental methods are necessary to cause effective hepatic failure. Chemical toxins such as D -galactosamine ( D -Galn) ( 1 ), thioacetamide ( 2 ), and carbon tetrachloride ( 3 ) have been used for this purpose. D -Galn is known as a toxin causing necrosis of the liver by UTP depletion and inhibition of protein synthesis ( 4 ). Recently, we reported that radical reactions were caused by D -Galn in the early stage based on a decrease in vitamin C ( 1 ), resulting in necrosis. In chemically induced hepatitis ( 1-3 ), liver vitamin C was firstly consumed by oxidative stress, indicating that vitamin C was the most sensitive indicator of oxidative stress ( 5 ).Antioxidants in foods are therefore expected to protect the liver from oxidative stress caused by these chemicals. To survey the antioxidative effect of food factors, it is necessary to investigate effects of a known antioxidant on the liver. Only limited studies are available and DMSO is reported to function as an antioxidant in cultured hepatocytes ( 6 ) as well as in the rat liver under thioacetamide intoxication (6)(7)(8). In this report, we have attempted to investigate whether DMSO functions in vivo as an antioxidant and protects against necrosis of the liver caused by D -Galn even in a pharmacological dose. For this purpose we evaluated oxidative stress using hepatic vitamin C level and activation profiles of the three major subclasses of the MAPK (mitogen a...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 54%

“…Determination was made as previously described ( 9 ). Homogenization was done basically as reported ( 12 ).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%