Geranylgeranylacetone protects against acetaminophen-induced hepatotoxicity by inducing heat shock protein 70

Nishida, Tadashi; Matsura, Tatsuya; Nakada, Junya; Togawa, Aki; Kai, Masachika; Sumioka, Isao; Minami, Yukari; Inagaki, Yoshimi; Ishibe, Yuichi; Ito, Hisao; Ohta, Yoshiji; Yamada, Kazuo

doi:10.1016/j.tox.2005.11.018

Cited by 32 publications

(27 citation statements)

References 43 publications

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“…Light microscopic examination of liver samples was assessed semiquantitatively by visual inspection of the sections, following the procedures of Valentovic et al (2004) and Nishida et al (2006). Sections of erdosteine groups showed no abnormality in liver histology.…”

Section: Light Microscopic Examination Resultsmentioning

confidence: 99%

Effects of Erdosteine on Acetaminophen-induced Hepatotoxicity in Rats

et al. 2008

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We investigated the effects of erdosteine on acetaminophen (APAP)-induced hepatotoxicity in rats. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), AST (aspartate aminotransferase), and ALT (alanine transaminase) activities, and malonyldialdehyde (MDA) and nitric oxide levels as oxidant/antioxidant biochemical parameters were investigated with light microscopic evaluation in adult female Wistar Albino rats. APAP administration produced a decrease in hepatic SOD, CAT, and GSH-Px activities, and coadministration of erdosteine (150 and 300 mg/kg) resulted in increases in the activities. MDA and NO levels increased in the APAP group, and erdosteine treatments prevented these increases. Significant elevations in serum AST and ALT levels were observed in the APAP group, and when erdosteine and APAP were coadministered, their serum levels were close to those in the control group. Light microscopic evaluation of livers showed that there were remarkable centrilobular (zone III) hepatic necrosis and mild to moderate sinusoidal congestion in the APAP group, whereas in the erdosteine group, cellular necrosis was minimal and the hepatocytes maintained a better morphology when compared to the APAP group. Erdosteine prevented APAP-induced liver injury and toxic side effects probably through the antioxidant and radical scavenging effects of erdosteine.

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Section: Light Microscopic Examination Resultsmentioning

confidence: 99%

Effects of Erdosteine on Acetaminophen-induced Hepatotoxicity in Rats

et al. 2008

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“…GGA has the ability to protect various cells from apoptosis triggered by a wide range of stimuli, including ethanol, reactive oxygen species, proteasome inhibitors, and nonsteroidal anti-inflammatory drugs and ischemia (Hirakawa et al, 1996;Ikeyama et al, 2001;Kikuchi et al, 2002;Nishida et al, 2006). It is worthwhile to note that all of these agents are potential inducers of ER stress.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent investigation revealed the novel potential of this agent as a general cytoprotective compound. GGA induces 70-kDa heat shock protein (HSP70) selectively, and it protects various cells from apoptosis in vitro triggered by ethanol, reactive oxygen species, proteasome inhibitors, and cytotoxic drugs (Hirakawa et al, 1996;Ikeyama et al, 2001;Kikuchi et al, 2002;Nishida et al, 2006). The therapeutic utility of GGA in vivo has also been documented by several investigators.…”

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confidence: 99%

Geranylgeranylacetone, an Inducer of the 70-kDa Heat Shock Protein (HSP70), Elicits Unfolded Protein Response and Coordinates Cellular Fate Independently of HSP70

Endo¹,

Hiramatsu²,

Hayakawa³

et al. 2007

Mol Pharmacol

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“…HSPs (also termed stress proteins) are induced by a number of stimuli including heat stress, exercise, and oxidative stress (Kregel 2002). Recent observations also indicate that HSPs may play an important role in the cellular defense against several toxic chemicals (Nishida et al 2006;Tolson et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Simulated diving after heat stress potentiates the induction of heat shock protein 70 and elevates glutathione in human endothelial cells

Djurhuus

Nossum

Lundsett

et al. 2010

Cell Stress and Chaperones

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Heat stress prior to diving has been shown to confer protection against endothelial damage due to decompression sickness. Several lines of evidence indicate a relation between such protection and the heat shock protein (HSP)70 and HSP90 and the major cellular red-ox determinant, glutathione (GSH). The present study has used human endothelial cells as a model system to investigate how heat stress and simulated diving affect these central cellular defense molecules. The results demonstrated for the first time that a simulated dive at 2.6 MPa (26 bar) had a potentiating effect on the heat-induced expression of HSP70, increasing the HSP70 concentration on average 54 times above control level. In contrast, a simulated dive had no significant potentiating effect on the HSP90 level, which might be due to the higher baseline level of HSP90. Both 2 and 24-h dive had similar effects on the HSP70 and HSP90, suggesting that the observed effects were independent of duration of the dive. The rapid HSP response following a 2-h dive with a decompression time of 5 min might suggest that the effects were due to compression or pressure per se rather than decompression and may involve posttranslational processing of HSP. The exposure order seemed to be critical for the HSP70 response supporting the suggestion that the potentiating effect of dive was not due to de novo synthesis of HSP70. Neither heat shock nor a simulated dive had any significant effect on the intracellular GSH level while a heat shock and a subsequent dive increased the total GSH level approximately 62%. Neither of these conditions seemed to have any effect on the GSH red-ox status.

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Geranylgeranylacetone protects against acetaminophen-induced hepatotoxicity by inducing heat shock protein 70

Cited by 32 publications

References 43 publications

Effects of Erdosteine on Acetaminophen-induced Hepatotoxicity in Rats

Effects of Erdosteine on Acetaminophen-induced Hepatotoxicity in Rats

Geranylgeranylacetone, an Inducer of the 70-kDa Heat Shock Protein (HSP70), Elicits Unfolded Protein Response and Coordinates Cellular Fate Independently of HSP70

Simulated diving after heat stress potentiates the induction of heat shock protein 70 and elevates glutathione in human endothelial cells

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