• Nutrition Research and Practice
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• v.7 no.2
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• pp.109-114
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• 2013

We compared the preventive capacity of high intakes of vitamin C (VC) and vitamin E (VE) on oxidative stress and liver toxicity in rats fed a low-fat ethanol diet. Thirty-two Wistar rats received the low fat (10% of total calories) Lieber-DeCarli liquid diet as follows: either ethanol alone (Alc group, 36% of total calories) or ethanol in combination with VC (Alc + VC group, 40 mg VC/100 g body weight) or VE (Alc + VE group, 0.8 mg VE/100 g body weight). Control rats were pair-fed a liquid diet with the Alc group. Ethanol administration induced a modest increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), conjugated dienes (CD), and triglycerides but decreased total radical-trapping antioxidant potential (TRAP) in plasma. VE supplementation to alcohol-fed rats restored the plasma levels of AST, CD, and TRAP to control levels. However, VC supplementation did not significantly influence plasma ALT, AST, or CD. In addition, a significant increase in plasma aminothiols such as homocysteine and cysteine was observed in the Alc group, but cysteinylglycine and glutathione (GSH) did not change by ethanol feeding. Supplementing alcohol-fed rats with VC increased plasma GSH and hepatic S-adenosylmethionine, but plasma levels of aminothiols, except GSH, were not influenced by either VC or VE supplementation in ethanol-fed rats. These results indicate that a low-fat ethanol diet induces oxidative stress and consequent liver toxicity similar to a high-fat ethanol diet and that VE supplementation has a protective effect on ethanol-induced oxidative stress and liver toxicity.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.51 no.1
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• pp.31-41
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• 2018

Seaweeds are composed of a variety of bioactive substances, including polysaccharides, pigments, minerals, peptides, and polyphenols. Among these substances, the arsenic content of seaweeds has been a significant cause for concern. The present study evaluated the toxicity of arsenic from three species of seaweed using a zebrafish Danio rerio model. The arsenic-rich extracts were obtained from Ecklonia cava (ECAE), Undaria pinnatifida (UPAE) and Hizikia fusiformis (HFAE) using a solvent of 50% methanol and 1% $HNO_3$. We investigated the toxicity of the arsenic-rich extracts in zebrafish embryos through survival rate, heart rate, yolk sac edema size, cell death, reactive oxygen species (ROS) production and real-time polymerase chain reaction (PCR). The hepatotoxicity of arsenic-rich extracts was assessed in the liver of adult zebrafish through real-time PCR and histopathology. The survival rates of embryos and adult zebrafish showed no significant changes at any concentration. At 100 ppm, embryos did not exhibit significant differences in heart rate, yolk sac edema size, cell death or ROS production. In addition, apoptosis-related genes in larvae and liver tissue were unaffected by treatment with arsenic-rich extracts. These data will help clarify that developmental changes, hepatic oxidative stress, and apoptosis are not associated with toxicity from arsenic-rich seaweed extracts in a zebrafish model.

• Nutritional Sciences
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• v.6 no.3
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• pp.141-147
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• 2003

Fruits and vegetables reportedly have a protective effect against hyperlipidemia and oxidative disease. Accordingly, this study aimed to investigate the lipid-lowering effect and antioxidative capacity of persimmon leaf extract (PLE) in rats fed a high-cholesterol diet. Male rats were fed a high-cholesterol (1% wt/wt) or high-cholesterol diet supplemented with Lovastatin (0.02% wt/wt) or PLE (0.2% wt/wt) for 5 weeks. The concentration of plasma total cholesterol was significantly lower in the PLE group than in the lovastatin group. However, the concentration of plasma HDL-cholesterol and the ratio of HDL-cholesterol/total-cholesterol (%) were significantly higher in the PLE group than in the control group. The PLE supplement also significantly lowered the contents of hepatic cholesterol and triglyceride. In comparing fecal sterol contents, the PLE group saw a significant increase of both neutral and acidic sterol compared to the other groups. The PLE supplement significantly lowered plasma GOT and GPT activity, which ave indices of hepatic toxicity. Plasma TBARS concentration was significantly lower in the PLE group than in the control group, while hepatic TBARS level was not significantly different between the groups. In a comparison of hepatic antioxidant parameters, SOD, catalase and GSH-Px activity were significantly higher in the PLE group than in the control group. However, the PLE supplement significantly towered antioxidant enzyme activity in the erythrocyte. Furthermore, these results suggest that supplementation of PLE promoted the excretion of fecal sterols, thereby leading to decreased absorption of dietary cholesterol. In addition, PLE may play an important role in regulating antioxidative capacities by altering SOD and ChT activity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7517-7522
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• 2015

Onion (Allium cepa) consumption has been remarked in folk medicine which has not been noted to be administered so far as an adjunct to conventional doxorubicin-based chemotherapy in breast cancer patients. To our knowledge, this is the first study aimed to investigate the effects of consuming fresh yellow onions on hepatic enzymes and cancer specific antigens compared with a low-onion containing diet among breast cancer (BC) participants treated with doxorubicin. This parallel design randomized controlled clinical trial was conducted on 56 BC patients whose malignancy was confirmed with histopathological examination. Subjects were assigned in a stratified-random allocation into either group received body mass index dependent 100-160 g/d of onion as high onion group (HO; n=28) or 30-40 g/d small onion in low onion group (LO; n=28) for eight weeks intervention. Participants, care givers and laboratory assessor were blinded to the assignments (IRCT registry no: IRCT2012103111335N1). The compliance of participants in the analysis was appropriate (87.9%). Comparing changes throughout pre- and post-dose treatments indicated significant controls on carcinoembryonic antigen, cancer antigen-125 and alkaline phosphatase levels in the HO group (P<0.05). Our findings for the first time showed that regular onion administration could be effective for hepatic enzyme conveying adjuvant chemotherapy relevant toxicity and reducing the tumor markers in BC during doxorubicin-based chemotherapy.

• Radiation Oncology Journal
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• v.34 no.3
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• pp.168-176
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• 2016

Purpose: The purpose of current study is to evaluate the response of the patients with portal vein thrombosis (PVT) or hepatic vein thrombosis (HVT) in hepatocellular carcinoma (HCC) treated with three-dimensional conformal radiation therapy (3D-CRT). In addition, survival of patients and potential prognostic factors of the survival was evaluated. Materials and Methods: Forty-seven patients with PVT or HVT in HCC, referred to our department for radiotherapy, were retrospectively reviewed. For 3D-CRT plans, a gross tumor volume (GTV) was defined as a hypodense filling defect area in the portal vein (PV) or hepatic vein (HV). Survival of patients, and response to radiation therapy (RT) were analyzed. Potential prognostic factors for survival and response to RT were evaluated. Results: The median survival time of 47 patients was 8 months, with 1-year survival rate of 15% and response rate of 40%. Changes in Child-Pugh score, response to RT, Eastern cooperative oncology group performance status (ECOG PS), hepatitis C antibody (HCVAb) positivity, and additional post RT treatment were statistically significant prognostic factors for survival in univariate analysis (p = 0.000, p = 0.018, p = 0.000, p = 0.013, and p = 0.047, respectively). Of these factors, changes in Child-Pugh score, and response to RT were significant for patients' prognosis in multivariate analysis (p = 0.001 and p = 0.035, respectively). Conclusion: RT could constitute a reasonable treatment option for patients with PVT or HVT in HCC with acceptable toxicity. Changes in Child-Pugh score, and response to RT were statistically significant factors of survival of patients.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.460-465
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• 2013

The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/$10{\mu}g/kg$ body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.

• Tuberculosis and Respiratory Diseases
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• v.63 no.5
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• pp.435-439
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• 2007

Standard antituberculous therapy, including isoniazid (INH), rifampin, ethambutol, and pyrazinamide (PZA), is widely used to treat active tuberculosis. The most important side effect is hepatotoxicity. In a standard four-drug regimen, PZA was the most common cause of drug-induced hepatitis and was dose-related. The incidence of drug-induced hepatitis is high at doses of 40~70 mg/kg per day but has fallen significantly since the recommended dose was reduced. Liver toxicity induced by PZA is rare at doses of 25 mg/kg per day or less. PZA-induced fulminant hepatic failure is also rare but fatal. We report a case of fulminant hepatic failure caused by a re-challenge of PZA.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.252-260
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• 2007

As it is needed to assay possible feasibility of extrapolation between in vivo and in vitro systems and to develop a new in vitro method for toxicity testing, we investigated global gene expression from both animal and cell line treated with thioacetamide (TAA) and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with TAA and sacrificed at 6 and 24 h. For in vitro study, TAA was administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose TAA-treated group, there was centrilobular necrosis (in vivo) and cellular toxicity with an elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified several common pathways existed between in vivo and in vitro system such as glutathione metabolism, bile acid biosynthesis, nitrogen metabolism, butanoate metabolism for hepatotoxicty caused by TAA. Our results suggest it may be feasible to develop toxicogenomics biomarkers by comparing in vivo and in vitro genomic profiles specific to TAA for application to prediction of liver toxicity.

• The Journal of Internal Korean Medicine
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• v.24 no.2
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• pp.190-202
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• 2003

Object : The effect of Banhabakchulchunma-tang extracts on the hepatic, splenic and cardiac toxicity induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. Methods : The changes of body weight, clinical signs, necropsy findings and organ weights of liver, spleen and heart were observed with blood GOT and GPT levels. Results : 1. Decrease of body weight and The degrees of anorexia, ataxia and dehydration after Doxorubicin treatment were dose-dependently inhibited by Banhabakchulchunma-tang extracts. 2. Increase of absolute and relative liver and heart weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhabakchulchunma-tang extracts. In addition, the degrees of liver congestion necrotic spot and the degrees of heart congestion enlargement were dose-dependently decreased after Banhabakchulchunma-tang extracts dosing groups compared to that of doxorubicin treatment group. It is also demonstrated that elevated serum GOT and GPT levels in doxorubicin treatment group were significantly decreased in Banhabakchulchunma-tang extracts dosing groups. 3. Decrease of absolute and relative spleen weight observed in doxorubicin treatment group were dose-dependently inhibited by Banhabakchulchunma-tang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased after Banhabakchulchunma-tang extracts dosing groups compared to that of doxorubicin treatment group. Conclusion : the toxicity of doxorubicin treatment(decrease of body weights, clinical signs such as anorexia, ataxia and dehydration, changes of organ weights of liver, spleen and heart, elevation of serum GOT and GPT levels) was inhibited and/or prevented by Banhabakchulchunma-tang extracts. According to these results, it is considered that Banhabakchulchunma-tang has some preventive effect against to doxorubicin induced toxicity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1025-1034
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• 2009

This study was carried out to examine the protective effect of Cultured Wild Ginseng(CWG) on the acute and subacute toxicities induced by doxorubicin(Doxo) in mice. Heart and liver weight was decreased following Doxo administration. In contrast, such a decrease was significantly attenuated by CWG administration. The value of serum CPK in Doxo group was increased compared with normal group. But the value of CWG group were decreased significantly compared with the values of Doxo group in the liver of the Doxo group, cloudy swelling of hepatic cells and narrowing of sinusoids were observed. Whereas in the CWG group, well oriented hepatic cell cords and sinusoids were observed. In the testis of the Doxo group, necrotic and degenerative changes of the seminiferous tubules, especially beneath testicular membrane were observed. But those lesions were alleviated in CWG group. Cross sectional area of testis and diameter of semineferous tubule were significantly increased in CWG group compared with Doxo group. Body weight was reduced in Doxo group compared with normal group. In contrast, such a decrease was significantly attenuated by CWG administration atwa5th day. Spermatogenetic cells in seminiferous tubules were necrotic and desquamated and the cellularity of seminiferous epithelia was reduced in Doxo group. But those lesions were attenuated by CWG administration. Cross sectional area of testis and diameter of seminiferous tubule were significantly increased in CWG group compared with Doxo group. In addition, the increase in lipid peroxidation(LPO) in testis was inaddition, the, iout such a increased was significantly inhibited in CWG group. BrdU labelled cells in the seminiferous tubules were remarkably decreased in Doxo group. Whereas the number of seminiferous tubules labelled with BrdU in spermatogonia was increased by CWG administration. The obtained results suggest that CWG has protective effect on doxorubicin-induced toxicity. This effect might be mediated through the supplementation of vital energy.