Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease

Masubuchi, Yasuhiro; Bourdi, Mohammed; Reilly, Timothy P.; Graf, Mary L.; George, John W.; Pohl, Lance R.

doi:10.1016/s0006-291x(03)00572-2

Cited by 136 publications

(100 citation statements)

References 41 publications

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“…In the present study, the TNF-α level was markedly increased in the APAPtreated group. This result agrees with in vitro and in vivo studies by Masubuchi et al (2003) and Matsumaru et al (2003) who reported that TNF-α has an important role for expression of hepatotoxicity by APAP. However, the TNF-α level in both doses of the PG pretreated groups significantly decreased compared with the APAP-treated group.…”

Section: +supporting

confidence: 93%

Protective effect of Panax ginseng against N-acetyl-p-aminophenol-induced hepatotoxicity in rats

Uzkeser¹

2012

Afr. J. Pharm. Pharmacol.

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Panax ginseng (PG) has been commonly used as medicinal herb for the treatment of various diseases in Eastern Asia for thousands of years. This study was designed to investigate the protective effect of PG against paracetamol-(N-acetyl-p-aminophenol; APAP)-induced liver damage in rats. Thirty-two albino Wistar rats were divided into four groups: Group C (control); Group APAP (gavaged orally with APAP (APAP, 2 g/kg, single dose); Group PG 100 mg/kg + APAP or 200 mg/kg + APAP (these two groups were treated by gavaging with PG (100 or 200 mg/kg) for 30 days following a single dose of APAP). APAP treatment alone induced hepatotoxicity, evidenced by significant increases in malondialdehyde (MDA) level and serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α). In addition, the level of GSH in the liver was significantly reduced, as were the activities of superoxide dismutase (SOD) and catalase (CAT). Liver histopathological examination showed that APAP administration induced centrilobular necrosis and infiltration of lymphocytes. However, these biochemical and histological changes were prevented by PG pretreatment. In conclusion, our results suggest that PG may be considered a protective medicinal herb against APAP-induced liver injury.

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Section: +supporting

confidence: 93%

Protective effect of Panax ginseng against N-acetyl-p-aminophenol-induced hepatotoxicity in rats

Uzkeser¹

2012

Afr. J. Pharm. Pharmacol.

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“…43 In addition,, Hsps have been implicated in the protection against APAP-induced necrosis-like liver failure. 44 After NTBC withdrawal, we observed a marked increase of Hsp27, 32, and 70. The up-regulation of multiple Hsps, which have been shown to prevent cell death by either apoptosis or necrosis, strongly suggests that they contribute to the acquired phenotype in mice that are off NTBC.…”

Section: Discussionmentioning

confidence: 79%

Chronic liver disease in murine hereditary tyrosinemia type 1 induces resistance to cell death

et al. 2004

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“…[34][35][36] These observations would indicate the essential involvement of inflammatory responses in the development of liver damages caused by APAP. Accumulating evidence implicates IL-1a and IL-1b as crucial mediators in various inflammatory reaction 11,[13][14][15] and their endogenous antagonist, IL-1ra, can inhibit the biological activities of IL-1s by competitive binding to IL-1RI.…”

Section: Discussionmentioning

confidence: 84%

“…By contrast, there was no significant difference in the intrahepatic expression of IL-6 and IL-10, the cytokines that had protective roles in APAP-induced liver injury (data not shown). 34,35 These observations would imply that impaired NAPQI generation in IL-1ra KO mice reduced the initiation of APAP-induced liver injury and subsequent inflammatory reactions as evidenced by reduced IL-1 and chemokine expression.…”

Section: Il-1ra and Apap-induced Liver Injury T Ishibe Et Almentioning

confidence: 97%

Reduced acetaminophen-induced liver injury in mice by genetic disruption of IL-1 receptor antagonist

Ishibe

Kimura

Ishida

et al. 2009

Laboratory Investigation

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Acetaminophen (APAP) induced increases in intrahepatic expression of interleukin (IL)-1a, IL-1b, and IL-1 receptor antagonist (IL-1ra), when administered intraperitoneally. These observations prompted us to define the pathophysiological roles of IL-1ra in APAP-induced liver injury. Compared with wild-type (WT) mouse-derived hepatocytes, IL-1ra-deficient (IL-1ra KO)-derived hepatocytes exhibited more resistance against APAP but not APAP-derived major toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Moreover, the amounts of a major APAP adduct (selenium-binding protein), an indicator of NAPQI generation from APAP, was significantly lower in IL-1ra KO mice than WT mice with depressed intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, the enzymes crucially involved in NAPQI generation from APAP. These observations would indicate that IL-1ra deficiency impaired APAP metabolism. IL-1a and IL-1b were expressed to similar extents in livers of untreated IL-1ra KO and WT mice. By contrast, the intranuclear amount of p65 of NF-kB, which can suppress the gene expression of CYP1A2, CYP2E1, and CYP3A11, was higher in untreated IL-1ra KO than WT mice. Moreover, when mice were intraperitoneally administered APAP (200 mg/kg), IL-1ra KO mice exhibited attenuated APAP-induced liver injury as evidenced by reductions in serum alanine transferase levels and histopathological changes such as centrilobular necrosis, hemorrhages, and leukocyte infiltration. Finally, when given 12 h before APAP challenge, IL-1a repressed the intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, eventually reducing APAP-induced liver injury, along with reduction in APAP adducts. Collectively, NF-kB was activated without any stimuli by the genetic disruption of IL-1ra, and suppressed cytochrome P450 enzyme expression, thereby reducing APAP-induced liver injury.

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Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease

Cited by 136 publications

References 41 publications

Protective effect of Panax ginseng against N-acetyl-p-aminophenol-induced hepatotoxicity in rats

Protective effect of Panax ginseng against N-acetyl-p-aminophenol-induced hepatotoxicity in rats

Chronic liver disease in murine hereditary tyrosinemia type 1 induces resistance to cell death

Reduced acetaminophen-induced liver injury in mice by genetic disruption of IL-1 receptor antagonist

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