• Toxicological Research
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• v.29 no.3
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• pp.165-172
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• 2013

Acetaminophen (APAP) known as paracetamol is the main ingredient in Tylenol, which has analgesic and anti-pyretic properties. Inappropriate use of APAP causes major morbidity and mortality secondary to hepatic failure. Overdose of APAP depletes the hepatic glutathione (GSH) rapidly, and the metabolic intermediate leads to hepatocellular death. This article reviews the mechanisms of hepatotoxicity and provides an overview of current research studies. Pharmacokinetics including metabolism (activation and detoxification), subsequent transport (efflux)-facilitating excretion, and some other aspects related to toxicity are discussed. Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene battery plays a critical role in the multiple steps associated with the mitigation of APAP toxicity. The role of Nrf2 as a protective target is described, and potential natural products inhibiting APAP toxicity are outlined. This review provides an update on the mechanism of APAP toxicity and highlights the beneficial role of Nrf2 and specific natural products in hepatoprotection.

• BMB Reports
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• v.39 no.5
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• pp.479-491
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• 2006

Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.

• Herbal Formula Science
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• v.16 no.2
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• pp.193-204
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• 2008

Dehydrocostus lactone (DHL) and Mokko lactone (ML) were isolated from Saussureae Radix, and their effects on heme oxygenase-1 (HO-1) expression and hepatoprotection in the liver cell line HepG2 were investigated. DHL induced HO-1 expression and HO activity in a dose-dependent manner, whereas ML lacking one double bond property at 11 and 13 carbons on its own chemical structure had no apparent effects. DHL also induced Nrf2 nuclear translocation and enhanced antioxidant response element (ARE) activation which mediated HO-1 gene transcription. Pretreatment with DHL protected HepG2 cells against oxidative damages caused by H2O2. Interestingly, the hepatoprotective effects of DHL appeared to be associated with HO enzymatic activation, HO-1 expression and Nrf2 activation, because blockage of HO activity by a HO inhibitor and inhibition of HO-1 and Nrf2 cellular synthesis by small interfering RNA abolished heptoprotection afforded by DHL. Taken together, this investigation provides evidence supporting that Saussureae Radix is hepatoprotective against oxidative stress that causes abnormal liver damages.

• Preventive Nutrition and Food Science
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• v.8 no.3
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• pp.239-244
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• 2003

Recently, we reported (J Korean Soc Food Sci Nutr, 31(3): 516-520, 2002) that Semisulcospira libertina (Marsh Snail) pretreatment has a hepatoprotective effect on $CCl_4$-induced liver damage in rats. The purpose of this study was to investigate the possible mechanisms of hepatoprotection by S. libertina (SL) on liver injury induced by acetaminophen (AA). Male ICR mice were pretreated with dehydrated powder of SL once daily for three consecutive days, given a single toxic dose of AA (450 mg/kg) and liver function determined 24 h later. Liver damage was assessed by quantifying serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) activities, and by measuring hepatic lipid peroxidation. To confirm possible mechanism(s), the content of hepatic glutathione (GSH) and gene expression of tumor necrosis factor a (TNF $\alpha$) mRNA by reverse transcription-polymerase chain reaction (RTPCR) were also measured. Pretreatment with SL dramatically lowered AA-elevated ALT, AST and SDH activities. SL pretreatment decreased AA-produced lipid peroxidation by 11% and restored the AA-depleted hepatic GSH by 27%. Furthermore, SL markedly suppressed the expression of TNF $\alpha$ mRNA induced by AA. Our findings revealed that the possible hepatoprotective mechanisms of SL could be attributed, at least in part, to the glutathione-mediated detoxification as well as the regulation of TNF $\alpha$ mRNA expression.

• The Korean Journal of Food And Nutrition
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• v.33 no.1
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• pp.17-26
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• 2020

This study was conducted to evaluate the functionality of fermented black garlic extracts under various conditions. Black garlic powder was prepared by aging for 0~72 hours at 80℃ depending on relative humidity (RH). It showed the highest antioxidant effects among the samples; the total antioxidant activity of black garlic powders at RH 75%, 84%, and 90% for 72 hours was increased 31.9 times, 28.2 times, and 22.6 times compared with that of the fresh garlic powder, respectively. Also, the alliin content was gradually decreased. S-ally-L-cysteine and S-ethyl-cysteine levels were increased; the highest values were 495.9 ㎍/g and 1,769.7 ㎍/g after aging for 72 hours at RH 75%. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were increased following high fat diet feeding, but the rise was obviously reduced by administration of black garlic extract. The total cholesterol, LDL/VLDL-cholesterol, and triglyceride contents in serum were significantly lower in methionine and choline deficient (MCD) diet treatment groups than in the positive control group. The concentration was increased following the intake of black garlic and fermented black garlic extracts. Therefore, black garlic extracts could be an ideal material as a dietary supplement in healthy functional foods to improve the effects on fatty liver.

• YAKHAK HOEJI
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• v.52 no.4
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• pp.316-321
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• 2008

The hepatoprotection by the methanol extract of Oenanthe javanica DC (water dropwort) (OJME) was investigated in Sprague Dawley rats with inducing liver damage by acetaminophen. After OJME administration for 1 week, the increase of hepatic lipid peroxide level by acetaminophen-induced hepatotoxicity was significantly reduced. In case of phase I microsomal enzyme systems including cytochrome P-450, aminopyrine N-demethylase and aniline hydroxylase, any significant differences between in control and in OJME-pretreated group was observed after acetaminophen treatment. However, the pretreatment of OJME maintained the hepatic glutathione level and the activity of liver cytosolic glutathione S-transferase, which was significantly decreased by the acetaminophen intoxication. Among the glutathione-generating system, glutathione reductase was more responsible for its biosynthesis rather than ${\gamma}-glutamylcystein$ synthetase. OJME itself showed the strong inhibition activity on DPPH radical generation. In conclusion, OJME administration maintains the liver glutathione pool and hepatic glutathione S-transferase activity, in addition with its high anti-oxidative capability, to show hepatoprotective effect from acetaminophen intoxication.

• BMB Reports
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• v.46 no.10
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• pp.513-518
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• 2013

We investigated the protective effects of Gymnaster koraiensis against oxidative stress-induced hepatic cell damage. We used two different cytotoxicity models, i.e., the administration of tert-butyl hydroperoxide (t-BHP) and acetaminophen, in HepG2 cells to evaluate the protective effects of G. koraiensis. The ethyl acetate (EA) fraction of G. koraiensis and its major compound, 3,5-di-O-caffeoylquinic acid (DCQA), exerted protective effects in the t-BHP-induced liver cytotoxicity model. The EA fraction and DCQA ameliorated t-BHP-induced reductions in GSH levels and exhibited free radical scavenging activity. The EA fraction and DCQA also significantly reduced t-BHP-induced DNA damage in HepG2 cells. Furthermore, the hexane fraction of G. koraiensis and its major compound, gymnasterkoreayne B (GKB), exerted strong hepatoprotection in the acetaminophen-induced cytotoxicity model. CYP 3A4 enzyme activity was strongly inhibited by the extract, hexane fraction, and GKB. The hexane fraction and GKB ameliorated acetaminophen-induced reductions in GSH levels and protected against cell death.

• Food Science and Biotechnology
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• v.17 no.6
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• pp.1178-1184
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• 2008

The effect of some peptides on hepatoprotection and cecal fermentation against D-galactosamine (GalN)-treated rats was studied. In acute hepatic injury tests, serum alanine aminotransferase (ALT), aspartate aminotranferase (AST), and lactic dehydrogenase (LDH) activities were remarkably increased after injection of GalN. However, potato and soybean peptides significantly decreased GalN-induced alterations of serum ALT and AST activities. Hepatic thiobarbituric acid-reactive substance (TBARS) concentration in GalN-treated groups fed potato and soybean peptides was significantly lower than that in GalN-treated control group. Hepatic glutathione level in the GalN-treated group fed potato peptide was significantly higher than that in GalN-treated control group. Furthermore, cecal Lactobacillus level in GalN-treated groups fed potato and soybean peptides was significantly higher than that in GalN-treated control group, and cecal short-chain fatty acid concentrations in GalN-treated group fed potato peptide were significantly higher than in GalN-treated control group. These results indicate that potato peptide may improve the cecal fermentation and prevent the GalN-induced liver damage in rats.

• Natural Product Sciences
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• v.13 no.3
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• pp.186-189
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• 2007

The aerial parts of Verbascum sinaiticum Benth. (Scrophulariaceae) yielded two iridoids that were idenified as ajugol 3 and aucubin 4. Also, investigation of the flavonoid constituents revealed the isolation and identification of luteolin 1 and chrysoeriol-7-glucoside 2. All the isolated compounds were identifid by spectroscopicmethods (UV, MS, $^{1}H-NMR$ and $^{13}C-NMR$) and in comparison with the literature data. Both alcohol and methylene chloride/methanol extracts (1 : 1) exhibited a hepatoprotective effect by $CCl_{4}challenge$ test.

• Food Science and Biotechnology
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• v.17 no.1
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• pp.199-202
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• 2008

The effects of $\beta$-(1,6)-galactosyl trehalose trisaccharide ($\beta$-GT) that was preferentially produced by Escherichia coli $\beta$-galactosidase on cryo- and thermo-protections of protein were investigated with those of other sugars at the level of 8% (w/v). As compared to a control without sugar additive, $\beta$-GT effectively enhanced 32-54% of the cryoprotection of fish actomyosin against repeated freeze-thawing and frozen storage, and also 49% of the protection against thermal inactivation of pyrophosphatase, respectively. As a result, it was significantly more effective than sorbitol and trehalose in both cryoprotection and thermoprotection. Thus, $\beta$-GT would be possibly applied as a sugar substitute for cryo- and thermo-protective applications of food protein.