• BMB Reports
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• v.40 no.6
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• Toxicological Research
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• v.32 no.2
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• pp.133-140
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• 2016

Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.1
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• pp.78-82
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• 2004

Effects of the extract of oriental herbal composition, Jang Baek Union (JBU), on hangover and liver function were studied in rats. To investigate anti-hangover effect, alcohol concentration and acetaldehyde concentration of blood were measured after oral ethanol treatment. Blood alcohol concentration was significantly reduced by pre-treatment of JBU extract. The effect of JBU extract on the blood acetaldehyde concentration was more significant than commercial product used as a positive control. To investigate hepato-protective effect, serum GOT and GPT levels and histological changes of liver tissue were analyzed in $CCl_4$-treated rats. JBU extract adminstration significantly inhibited the increase of serum GPT and GOT levels induced by $CCl_4$-treatment. Moreover, histological injuries of liver tissue such as fatty changes and sinusoidal leukocytosis were inhibited by JBU extract.

• Korean Journal of Food Science and Technology
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• v.31 no.3
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• pp.802-808
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• 1999

An rat liver enzyme test was carried out in order to investigate preventing effect of selested amino acids and some food extracts on ethanol induced liver toxicity in vitro. Solutions of aspartic acid, arginine, glutamic acid were prepared and treated on ethanol treated rat liver preparation. Protective effect of amino acids on lipid peroxidation was determined. Same experiments were conducted using aqueous extracts of Dried soybean sprout, Dried Alaskan pollack and Ganoderma lucidum. The TBA value indicating the lipid peroxidation decreased significantly (p<0.05) by addition of aspartate, glutamate and arginine, repectively at concentrations of $6.25{\sim}50\;{\mu}g/mL$. Similar results were observed by adding the aqueous extracts of Soybean sprout, dried Alaskan pollack and Ganoderma lucidum. The aqueous extracts added after ethanol treatment presemted more effect than added before the treatment.

• Korean Journal of Pharmacognosy
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• v.40 no.2
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• pp.137-142
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• 2009

Isoniazid was discovered in 1950's and since then it has been widely used as a synthetic bactericidal agent in the treatment of tuberculosis. However, the adverse effect of isoniazid has been reported to show significant hepatotoxicity in approximately 1-2% of patients. Nitrofurantoin {1-(5-nitro-2-furfurylideneamino)-hydantoin} is a synthetic nitrofuran that is commonly used for the treatment and prophylaxis of urinary tract infections, but its use is associated with liver cirrhosis and fatal liver necrosis. Therefore, studies for natural products with protective effect on the isoniazid- and/or nitrofurantoin-induced hepatotoxcity would be valuable as the potential therapeutic use. 107 plants sources were collected at Mt. Baekdu, and extracted with methanol. These extracts had been screened for the protective effects against isoniazid- and/or nitrofurantoin-induced cytotoxicity in HepG2 cells at the both 100 and $300{\mu}g/ml$. Five methanolic extracts, Acanthopanax senticosus, Acer mono, Asparagus schoberioides, Fagopyrum tataricum, Potentilla centigrana, showed significant protective effects against isoniazidinduced hepatotoxicity. Two methanolic extracts, Acer mono and Leonurus artemisia, showed significant protective effects against nitrofurantoin-induced cytotoxicity in HepG2 cells.

• The Korea Journal of Herbology
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• v.24 no.3
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• pp.13-19
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• 2009

Objectives : This study was aimed to define the protective effect of Tissue Cultured Root of Wild Ginseng (CWG) against doxorubicin (Doxo) toxicity, and investigate the anti-tumor synergic effect of CWG in combination with Doxo in tumor-bearing C57BL/6 mice. Methods : Tumor-bearing mice were established by single inoculation with B16/F10 melanoma cells (2$\times$10$^6$/ml) subcutaneously. Tumor-bearing mice (tumor volume between 50-100 mm$^3$) were selected and divided them into control, Doxo, and Doxo+CWG group. Mice of Doxo group were received with Doxo (4 mg/kg of B.W.) intraperitoneally at 0, 4, 8 days after starting the experiment. Mice of Doxo+CWG group were received CWG water extract during 12 days in combination with Doxo treatment. The body weight, tumor volume, tumor weight, and organ weight (heart, liver, kidney, and testis) were measured. And serum SPK, GOT and creatinine values were analysed. Results : The volume and weights of tumor masses in Doxo group were decreased significantly compared with the those of control group. And the those of Doxo+CWG group were not significantly different from the those of Doxo group. Whereas the weight of body, liver, kidney and testis in Doxo+CWG group were increased significantly compared with the those of Doxo group. The level of serum CPK and GOT in Doxo group were increased compared with the those of control group. But the value of Doxo+CWG group were decreased significantly compared with the values of Doxo group. Conclusions : These results suggest that CWG has protective effect against doxorubicin toxicity. And these effect is guessed that is caused in augmentation of vital energy.

• Natural Product Sciences
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• v.20 no.4
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• pp.237-242
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• 2014

Plant extracts produced from branches of Crataegus pinnatifida and barks of Crataegus pinnatifida inhibited ethanol-induced cytotoxicity and DNA damage in liver cells. Furthermore, these two extracts inhibited the expression and activities of CYP2E1 enzyme. Cinnamomum cassia had a better effect on inhibition of DNA damage than Crataegus pinnatifida, as well as showed a high tendency to inhibit CYP2E1 expression and catalytic activities. It is considered that extracts produced from Crataegus pinnatifida or Cinnamomum cassia have an effect to reduce ethanol-induced cytotoxicity and DNA damage in liver cells. Therefore, we suggest to use Crataegus pinnatifida and Cinnamomum cassia and their ingredients as potential candidate substances to prevent and treat ethanol-induced cytotoxicity and genotoxicity in liver cells.

• Natural Product Sciences
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• v.22 no.4
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• pp.231-237
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• 2016

Prolonged alcohol consumption causes alcoholic liver damage due to the generation of reactive oxygen species, the accumulation of fatty acids, and an increase in inflammatory cytokines in the liver. In this study, the protective effect of a fruit extract of Paeonia anomala (FEPA) against chronic alcohol-induced liver damage was evaluated in Sprague-Dawley rats fed an ethanol or a control Lieber-DeCarli diet for 5 weeks to induce alcoholic liver damage. FEPA (50, 25, and 10 mg/kg body weight/day) as well as the reference control silymarin (25 mg/kg body weight/day) were administered along with the ethanol diet. FEPA protected against increases in alanine aminotransferase and aspartate aminotransferase in serum and attenuated alcohol-induced increases in triglycerides, tumor necrosis factor alpha, thiobarbituric acid-reactive substances, and cytochrome P450 2E1 enzyme activity in the liver compared with the group treated with ethanol only. Anti-oxidative defenses such as the total glutathione level and glutathione peroxidase activity were increased by FEPA treatment. These results suggest that FEPA exerts protective effects against chronic alcohol-induced liver damage by attenuating hepatosteatosis and pro-inflammatory cytokine production and enhancing anti-oxidative defense mechanisms in the liver.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.8
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• pp.1107-1112
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• 2011

Over-consumption of alcohol leads to many side-effects such as malnutrition, liver disease, and neuronal disorders and many investigators have tired to identify methods for preventing the side-effects of drinking. In this study, we demonstrated the protective effect of a new food component, SAC-1, containing Hovenia dulcis Thumb and Lonicera caerulea Thumb extract against the side-effects of drinking. We observed that blood alcohol concentration, glutamic oxaloacetate transaminase, lipid peroxidation, and total glutathione level decreased significantly in plasma and liver of mice fed the SAC-1 extract before alcohol intoxication. In particular, SAC-1 had more of a protective effect than that of Hovenia dulcis Thumb extract alone. These results suggest that SAC-1 should further be developed to treat alcohol detoxification and stimulate antioxidative potentials.

• Environmental Analysis Health and Toxicology
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• v.23 no.4
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• pp.325-335
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• 2008

The protective effects of the Naringin, on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with Naringin prior to the administration of $CCl_4$ significantly prevented an increase in serum alanine, aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with Naringin also significantly prevented the depletion of glutathione (GSH) content in the livers of $CCl_4$-induced mice. However, reduced hepatic glutathione levels was unaffected by treatment with Naringin alone. In addition, Naringin prevented $CCl_4$-induced apoptosis and necrosis, as indicated by a liver DNA laddering. To determine whether caspase-8,-3 pathway involved in $CCl_4$-induced acute liver injury, caspase-8, -3 activities were tested by ELISA. Naringin attenuated $CCl_4$induced caspase-8, -3 activities in mouse livers. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic study. The effects of Naringin on the cytochrome P450 (CYP) 2E1, the major isozyme involved in $CCl_4$ were also investigated. Treatment of mice with Naringin resulted in a significant decrease of the CYP2E1-dependent hydroxyl at ion and aniline in a dose-dependent manner. These findings suggest that protective effects of Naringin against the $CCl_4$-induced hepatotoxicity may be due to its ability to block CYP2E1-mediated $CCl_4$ bioactivation and that is also protects against caspase-8, -3 pathway mediated apoptosis.