• Bulletin of the Korean Chemical Society
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• v.28 no.6
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• pp.977-982
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• 2007

For the development of novel hepatoprotective agents, C2, C3, C23 and C28 functional groups on asiatic acid were modified, and the prepared compounds were evaluated for their hepatoprotective effects. Among the prepared compounds, 9, 13 and 16 showed significant hepatoprotective activities against CCl4- and galactosamine (GaIN)-induced hepatotoxicity. Especially, compound 9 showed the most significant hepatoprotective effects against GaIN-induced hepatotoxicity (66.4% protection at 50 μM) and moderate hepatoprotective activities against CCl4-induced hepatotoxicity (20.7% protection at 50 μM).

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.6
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• pp.1173-1180
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• 1997

Hepatotoxicity of caffeine and acetaminophen was investigated in this study. Special attention was paid to the effect of vitamins on the reduction of hepatotoxicity caused by the chemicals. Rat hepaocytes isolated by two-step perfusion method were cultured in two differents methods-suspension, monolayer cultures-, and exposed to caffeine and/or acetaminophen for 24hrs. Caffeine or acetaminophen exhibited no significant hepatotoxicity in terms of intracellular glutathione(GSH) level and lipid peroxidation(MDA), but GSH level was significantly decreased after administrated acetaminophen, and the toxicity caused by the chemicals showed a dose-dependent manner. The synergistic effect of caffeine and acetaminophen was observed when both caffeine and acetaminophen were supplemented to culture medium. At the concentration 1mM, caffeine enhanced the intracellular GSH depletion and MDA formation by 63% and 64%, respectively, compared to single supplementation of 10mM acetaminophen in culture medium. This hepatotoxicity induced membrane integrity loss was observed by lightmicroscope on the simultaneous administration of caffeine and acetaminophen in monolayer cultured hepatocytes. Co-supplementation of vitamins with caffeine/acetaminophen to culture medium results in the protection of hepatocytes from hepatotoxic attach by caffeine/acetaminophen. Especially, vitamin E was superior to vitamin C and $\beta$-carotene from the standpoints of GSH depletion and MDA formation. From this results, it has been speculated that vitamin E may play a role of antioxidant scavenging radicals produced from acetaminophen. Taken all together, in vitro culture system like monolayer culture of hepatocytes may be a useful tool for the evaluation of hepatotoxicity or protection ability of food ingredients.

• The Journal of Korean Medicine
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• v.23 no.3
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• pp.33-42
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• 2002

Objective : This study was performed to investigate the activity of Whagan-Jeon (huaganjian) in protection against acetaminophen (AAP)-induced hepatotoxicity and the possible mechanisms in vivo. Methods : The following were performed : Serum ALT, depletion of hepatic glutathione (GSH) levels, the microsomal p. nitrophenol hydroxylation activity, microsomal aniline hydroxylation activity, genomic DNA fragmentation and its reversal, hepatic glutathione-S-transferase (GST) activity, and hepatic NAD(P)H:quinone oxidoreductase (QR) activity Results : Whagan-Jeon (huaganjian) protected against AAP-inducedhepatotoxicity by the increase of GSH levels, inhibition of P450 2E1-specific metabolic activities, attenuation of hepatic DNA damage, and induction of GST and QR activities in vivo. Conclusions : In conclusion, Whagan-Jeon (huaganjian) was effective in protection against AAP-induced hepatoxicity.

• YAKHAK HOEJI
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• v.42 no.6
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• pp.598-606
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• 1998

The liver expresses a considerable amount of nitric oxide (NO) upon induction with cytokines or/and endotoxin. The NO synthesized by inducible NO synthase (NOS) of the liver see ms to play a role in various hepatic physiological processes. Here we investigate the effects of NO on acetaminophen (AA)-induced liver injury. The treatment of S-nitros-N-acetyl penicillamine (SNAP, exogenous NO donor) at the dose of 0.1mM decreased AA-induced hepatotoxicity suggesting the possibility of NO to play a role in protection from the hepatotoxicity induced by AA. On the other hand, the excessive NO produced by NO donor (SNAP: 0.5, 2.5, 6.25mM) has been shown to cause a concentration dependent hepatotoxicity, and such damages was decreased by Superoxide and increased by superoxide dismutase, indicating that the hepatotoxicity induced by excessive NO depends on balancing between NO and superoxide. Taken together, the results indicate that NO has biphasic effects on hepatotoxicity.

• Toxicological Research
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• v.9 no.2
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• pp.167-175
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• 1993

Protective effects of dithiol malonate derivatives (DMDs), YH-100, YH-150 and YH-439 on carbon tetrachloride-induced hepatotoxicity were investigated in primary rat hepatocytes culture. Treatment of DMDs to hepatocytes culture did not affect total cytochrome P-450 content and ECOD and AHH activities. Protein and RNA synthesis was also similar to control. Meanwhile, DMDs significantly decreased LDH release and in vitro lipid peroxidation induced by $CCI_4$. Accumulation of cellular triglyceride and decreased secretion of VLDL from liver cells by $CCI_4$ treatment were also significantly protected.

• Archives of Pharmacal Research
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• v.16 no.1
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• pp.13-17
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• 1993

Several naturally occurring furanocoumarins significantly inhibited microsomal lipid peroxidation not only mediated by endogeneous iron and NADPH but also initiated by $CCL_4$ metabolites, phellopterin, a potent inhibibitor of cytochrome p-450, exhibited an almost complete inhibition of $CCL_4$-induced hepatotoxicity as measured by sGPT activity 24 hr after $CCL_4$ intoxication, whereas other furanocoumarins such as imperation, byakangelicin and oxypeucedanin methanolate exerted no protective effect. When compared with other cytochrome P-450 inhibitors(SKF-52A, AIA) and silymarin given at the same dose level $(ED_{50})$, phellopterin still showed a significant inhibition of hepatotoxicity which was even stronger than that of AIA, known as a typical suicide inhibitor. Phellopterin was partially effective when given 30 min after $CCL_4$ treatment. Repeated administrations of phellopterin, however, resulted in a complete loss of the protection against $CCL_4$-induced hepatotoxicity.

• Journal of Pharmacopuncture
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• v.10 no.1 s.22
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• pp.101-107
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• 2007

Objectives : This study was aimed at investigating liver protection mechanism of Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese by inducing liver toxicity through $CCl_4$ and t-BHP in mice and evaluated serological findings. Methods : Experiment groups was categorized into untreated normal group, treated control group, and orally administered Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese experimental groups. At the termination of experiment, gross examination of the liver as well as Total bilirubin, AST, and ALT contents in the serum were evaluated. Results : 1. In the $CCl_4$ induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. 2. In the t-BHP induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. Conclusion : Taken together, Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese cannot be effectively used for recovering the liver functions in acute hepatotoxicity tests using $CCl_4$ and t-BHP. Further researches, for example treated long period, must be tried to verify the efficacies.

• Nutrition Research and Practice
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• v.9 no.1
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• pp.37-42
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• 2015

BACKGROUND/OBJECTIVES: Red grape seeds as functional food are a good source of important bioactive components such as phenolics and antioxidants, which decrease oxidative stress that contributes to the pathogenesis of hepatotoxicity. The current study was conducted in order to evaluate the protective effect of red grape dried seeds (RGDS) on antioxidant properties, lipid metabolism, and liver and kidney functions of rats with paracetamol (750 mg/kg) induced hepatotoxicity. MATERIALS/METHODS: RGDS was added to the basal diet at 5, 10, and 20%. Thirty five adult male rats were assigned to five groups (n = 7) for a six-week feeding period; group (1) normal control, group (2) induced control, groups (3, 4, and 5) fed a diet with RGPS at different levels, 5, 10, and 20%, respectively. At the end of the feeding period, animals' blood and tissues were collected for estimation of serum lipid profile, serum liver, and kidney biomarkers. The protection was measured by detecting lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), Catalase (CAT) (in liver tissues), and liver histological examination. RESULTS: The results showed a significant (P < 0.05) decrease in levels of serum cholesterol, triglycerides, low density lipoprotein (LDL-C), and very low density lipoprotein (VLDL-C), with a significant increase in level of high density lipoprotein (HDL-C) for RGDS groups compared to induced control. Rats administered a diet containing RGDS levels produced significant (P < 0.05) hepatoprotection by decreasing the activities of liver enzymes, kidney parameters, and lipid peroxidation, while levels of GSH, SOD, and CAT were increased significantly to near the normal levels. CONCLUSION: The RGDS 20% group was more effective than others against hepatotoxicity of paracetamol, which may be attributed to RGDS total phenols and antioxidant contents, which were 1.438 mg and 1.231 mg, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.15-23
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• 2016

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated $I{\kappa}B{\alpha}$ and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

• Korean Journal of Pharmacognosy
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• v.38 no.4
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• pp.400-402
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• 2007

Tacrine is an acetylcholinesterase inhibitor that is approved for the treatment of Alzheimer's disease. However, tacrine treatment for Alzheimer's disease results in reversible hepatotoxicity in 30-50% of patients, which seriously limits its clinical use. Accordingly, the identification of constituents in natural products that have protective effects on tacrine-induced hepatotoxicity would be valuable. In the present study, an immortalized human hepatoma cell line, HepG2 was employed to screen for agents that protect against tacrine-induced hepatotoxicity. The bioassay-guided fractionation of water extract of Cassiae Semen furnished two anthraquinones, aurantio-obtusin (1) and obtusifolin (2). Compounds 1 and 2 showed hepatoprotective effects with the protection ratio values of 55.3 +/- 0.5% and 41.2 +/- 0.8% at $160{\mu}M$, respectively.