Epigallocatechin-3-O-Gallate Protects Against Hepatic Damage and Testicular Toxicity in Male Mice Exposed to Di-(2-Ethylhexyl) Phthalate

Jian Ge,Baoyu Han,Huajun Hu,Jun Liu,Yang Liu 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.7

The aim of this study was to examine the effects of epigallocatechin-3-O-gallate (EGCG) on hepatic damage and testicular toxicity in male mice exposed to daily oral administration of di-(2-ethylhexyl) phthalate (DEHP). A mouse model was used to assess the effects of daily intraperitoneal EGCG injection on hepatic and testicular damage. Histological and mitochondrial membrane potential results revealed that EGCG treatment significantly arrested the progression of hepatic damage. EGCG treatment resulted in significant suppression of liver injury (i.e., reduced activities of alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). The development of DEHP-induced hepatic and testicular damage altered thetestosterone concentration in mouse serum, which could affect the reproductive ability of male mice. Moreover, EGCG treatment markedly attenuated testes lesions, sperm deformity, and spermatogenic cell apoptosis. At the molecular level, hepatic CYP3A4 expression was substantially reduced by EGCG treatment in mice exposed to DEHP compounds, whereas testicular aromatase expression was increased significantly in testes. Thus, these results demonstrate that EGCG administration may protect against liver damage and reproductive toxicity in males exposed to DEHP.

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice

역약곤,송가락,임양이,김용규,박건영 한국식품영양과학회 2015 Preventive Nutrition and Food Science Vol.20 No.1

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)- and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-, IL-1, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage.

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice

Yi, Ruo-Kun,Song, Jia-Le,Lim, Yaung-Iee,Kim, Yong-Kyu,Park, Kun-Young The Korean Society of Food Science and Nutrition 2015 Preventive Nutrition and Food Science Vol.20 No.1

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage.

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice

Ruo-Kun Yi,Jia-Le Song,Yaung-Iee Lim,Yong-Kyu Kim,Kun-Young Park 한국식품영양과학회 2015 Preventive Nutrition and Food Science Vol.20 No.1

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-? and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-?, IL-1?, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage.

黃芩으로 인한 간손상으로 판단되는 건선 환자 1례 보고

이기훈(Ki-Hoon Lee),양지은(Jieun Yang),장규태(Gyu Tae Chang) 대한한의학회 2011 대한한의학회지 Vol.32 No.4

Submicromolar bisphenol A induces proliferation and DNA damage in human hepatocyte cell lines <i>in vitro</i> and in juvenile rats <i>in vivo</i>

Kim, Seoyoung,Mun, Gil-im,Choi, Eun,Kim, Minjeong,Jeong, Ji Seong,Kang, Keon Wook,Jee, Sunha,Lim, Kyung-Min,Lee, Yun-Sil Elsevier 2018 Food and chemical toxicology Vol.111 No.-

<P><B>Abstract</B></P> <P>An association between bisphenol A (BPA) exposure and hepatic tumors was suggested, but the employment of high-dose levels raises questions about its relevance to human health. Here, we demonstrate that submicromolar concentrations of BPA induce the proliferation and DNA damage in human hepatocyte cell lines. In HepG2 and NKNT-3, undifferentiated and differentiated hepatocyte cell lines, respectively, submicromolar BPA concentrations promoted the cell proliferation, as indicated by enhanced DNA synthesis and elevated expression of cell-cycle proteins. At concentrations higher than 10 μM, these effects disappeared, reflecting a non-monotonic dose-response relationship. Notably, histone H2AX was activated following exposure to BPA, which is a sensitive marker of DNA damage. Importantly, proliferative foci and DNA damage were also observed in liver tissue of rats orally exposed to BPA at 0.5 mg/kg for 90 days, from juvenile age (postnatal day 9) through adulthood. Reactive oxygen species appeared to play a role in the BPA-induced proliferation and DNA damage, as evidenced by a partial reversal of both processes upon pretreatment with an antioxidant, <I>N</I>-acetylcysteine. Collectively, these results demonstrate that submicromolar BPA concentrations induce the DNA damage and promote the cell proliferation in the liver, which may support its role as a risk factor for hepatocarcinogenicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Submicromolar bisphenol A (BPA) concentrations induced proliferation and DNA damage in human hepatocyte cell lines. </LI> <LI> Proliferative foci and DNA damage were also observed in liver tissue of rats exposed to BPA. </LI> <LI> Histone H2AX activation, a sensitive marker of DNA damage, was observed after exposure of liver cells and tissues to BPA. </LI> <LI> The BPA-induced proliferative and DNA damage effects seemed to be mediated by the generation of reactive oxygen species. </LI> <LI> The study supports the role of BPA as a risk factor for hepatocarcinogenicity. </LI> </UL> </P>

Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis

Choi, Yoon Seok,Lee, Jeewon,Lee, Hyun Woong,Chang, Dong-Yeop,Sung, Pil Soo,Jung, Min Kyung,Park, Jun Yong,Kim, Ja Kyung,Lee, Jung Il,Park, Hana,Cheong, Jae Youn,Suh, Kyung-Suk,Kim, Hyung Joon,Lee, Jun BMJ Publishing Group Ltd 2015 Gut Vol.64 No.8

<P><B>Objective</B></P><P>Foxp3<SUP>+</SUP>CD4<SUP>+</SUP>CD25<SUP>+</SUP> regulatory T cells (Tregs) control immune responses, but their role in acute viral hepatitis remains elusive. Herein, we investigated alteration in the peripheral blood Treg population during acute hepatitis A (AHA) and its implication in the immune-mediated liver injury.</P><P><B>Design</B></P><P>The study included 71 patients with AHA, and peripheral blood mononuclear cells (PBMCs) were isolated. The suppressive activity of Treg population was determined by assessing anti-CD3/CD28-stimulated proliferation of Treg-depleted and reconstituted PBMCs. Treg cell frequency, phenotype and apoptosis in PBMCs were analysed by flow cytometry.</P><P><B>Results</B></P><P>The frequency of circulating Tregs was reduced during AHA. Moreover, the suppressive activity of the total Treg pool in the peripheral blood was attenuated during AHA. Treg frequency and suppressive activity of the Treg population inversely correlated with the serum alanine aminotransferase level. Fas was overexpressed on Tregs during AHA, suggesting their susceptibility to Fas-induced apoptosis. Indeed, increased apoptotic death was observed in Tregs of patients with AHA compared with healthy controls. In addition, agonistic anti-Fas treatment further increased apoptotic death of Tregs from patients with AHA. The decreased Treg frequency and Fas overexpression on Tregs were not observed in other acute liver diseases such as acute hepatitis B, acute hepatitis C and toxic/drug-induced hepatitis.</P><P><B>Conclusions</B></P><P>The size of the Treg pool was contracted during AHA, resulting from apoptosis of Tregs induced by a Fas-mediated mechanism. Decrease in Treg numbers led to reduced suppressive activity of the Treg pool and consequently resulted in severe liver injury during AHA.</P>

Acupuncture inhibits liver injury induced by morphine plus acetaminophen through antioxidant system

Lee, Young Joon,Zhao, Rong Jie,Kim, Young Woo,Kang, Su Jin,Lee, Eun Kyung,Kim, Nam Jun,Chang, Suchan,Kim, Jin Mook,Lee, Ji Eun,Ku, Sae Kwang,Lee, Bong Hyo Elsevier 2016 European journal of integrative medicine Vol.8 No.3

<P><B>Abstract</B></P> <P><B>Introduction</B></P> <P>Morphine (MP) and acetaminophen (APAP), widely used-pain relievers and antipyretics, are known to induce hepatotoxicity. Acupuncture, a traditional therapy in Asia, is used for various reasons including detoxification. This study aimed to examine whether acupuncture exerts protective effects against MP+APAP-induced hepatic damage.</P> <P><B>Methods</B></P> <P>Male Sprague-Dawley rats received chronic MP, withdrawal, and APAP. Thereafter, blood and liver were taken. Acupuncture was performed once daily. Asparte aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured, and percentages of abnormally decreased-hepatocyte regions, mean liver cell counts, and mean inflammatory cell numbers infiltrated on hepatic parenchyma were examined. In addition, antioxidant effects were evaluated based on liver lipid peroxidation malondialdehyde (MDA) and glutathione (GSH) contents, superoxide dismutase (SOD) and catalase (CAT) activities with the number of immunopositive hepatocytes against nitrotyrosine (NT) as a marker of inducible nitric oxide synthase (iNOS) related-oxidative stresses and 4-hydroxynonenal (4HNE) as a marker of lipid peroxidation.</P> <P><B>Results</B></P> <P>Significant elevations of AST and ALT were noted of MP or APAP. They also induced an increase in MDA contents as well as decreases in GSH levels and activities of SOD and CAT activity. A centrolobular decrease in hepatocytes along with degenerative changes of hepatocytes were also observed, and increases of NT and 4HNE immunoreactive hepatocytes were shown. These hepatocellular damages were more severe with the combination of MP+APAP. However, these MP+APAP-induced hepatic damages were significantly inhibited by acupuncture.</P> <P><B>Conclusion</B></P> <P>This study suggests that acupuncture may have a protective effect against the MP+APAP-induced hepatic damage through the amelioration of antioxidant defense systems.</P>

Vitamin C가 방사선과 Aflatoxin B1을 투여한 흰쥐의간 기능 효소 활성 및 간 손상에 미치는 효과

강진순 ( Jin Soon Kang ) 한국식품영양학회 2010 韓國食品營養學會誌 Vol.23 No.1

This study was conducted to determine the effects of vitamin C on the activity of liver function enzymes and electromicrographic changes in white rats treated with aflatoxin B1(AFB1) or X-ray and AFB1. Six week-old male Sprague-Dawley rats were randomly divided into five groups: a control group, AFB1 treated group, AFB1 treated group with vitamin C, X-ray and AFB1 co-treated group, X-ray and AFB1 co-treated group with vitamin C. On the first day of the experiment, only one dose of X-rays was exposed to the entire liver at 1,500 cGy. Next, vitamin C was injected at 10㎎/㎏body weight by intraperitoneal injection, followed 1 hr later by the administration of 0.4㎎/㎏of AFB1 by intraperitoneal injection. These treatments were then administered every three days over a period of 15 days. On the 16th day of treatments, the animals were sacrificed. Analysis of the activity of the liver function enzymes, GOT, ALK phatase and LDH, in the sera of rats revealed that they were somewhat increased by AFB1 treatment, X-ray and AFB1 co-treatment when compared to the control group. Furthermore, the activity of these enzymes decreased in response to administration of vitamin C. Especially, the levels of GOT were remarkably decreased in the AFB1 treated group treated with vitamin C when compared to the group treated with AFB1 alone(p<0.001). Electromicrographic analysis revealed cloudy swelling, necrosis, vesicular degeneration and fat accumulation of hepatocytes in response to treatment with AFB1 or co-treatment with X-ray and AFB1. However, the destruction of hepatic cells was considerably lower in the vitamin C-treated group. These results indicate that vitamin C had ameliorating effects on the hepatic cell damage.

자보양영환의 물추출물이 사염화탄소로 유발된 간 손상에 미치는 영향

전병훈,이형철,황상구,남은영,김대근,박정원,이영찬,박승택 한국생명과학회 2002 생명과학회지 Vol.12 No.2

자보양영환은 자보폐간의 효능이 있어 간허증상의 치료제로 사용되었던 전통약물로 잘 알려져 있다. 따라서 본 연구에서는 사염화탄소로 간 손상을 유도한 흰쥐에서 자보양영환의 물추출물이 간 보호효과가 있는지 알아보았다. 사염화탄소의 1회 복강투여는 혈청 aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)의 유의적인 증가가 관찰되어 사염화탄소에 의한 간 손상이 유발되었음을 알 수 있었다. 자보양영환 물 추출물(300, 600, and 1200 mg/kg, 7 days)을 전 처리한 횐쥐에서는 사염화탄소 단독 투여군인 대조군에 비해 AST, ALT, ALP의 유의한 감소양상이 관찰되었다. 또한 사염화탄소의 투여는 microsome의 지질과산화가 유도되었으며, 이물질대사효소(cytochrome P450 및 P450 reductase)의 유의한 감소가 확인되었다. 자보양영환 물추출물의 경구투여는 간의 지질과산화 지표인 microsome의 TBARS 생성을 억제하였으며 cytochrome P450 및 P450 reductase 활성도가 대조군에 비해 유의한 증가되어 정상수준으로 회복되었다. 자보양영환 추출물의 투여는 사염화탄소의 투여에 따른 생화학적 지표들의 변화를 억제하는데, 이러한 실험결과에서 자보양영환의 물추출물은 사염화탄소로 유도한 간 독성에 대하여 해독작용 및 간 보호효과가 있는 것으로 판단된다. Jaboyangyeong-hwan (IAE) has been known as a traditional medicine for the treatment of debility, fatigue, and liver diseases. The hepatoprotective effect of the water extract of Jaboyangyeong-hwan was investigated against carbon tetrachloride ($CCl_4$)-induced hepatic damage. A single intraperitoneal injection of $CCl_4$produced liver damage in rats as manifested by the significant rise of aspartate aminotransferase (AST, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in serum as compared to those of untreated normal group. Pretreatments of rats with the JAE extract (300, 600, and 1200 mg/kg for 7 days) were significantly reduced AST, ALT, and ALP levels compared with $CCl_4$-treated control group. Treatment of rats with $CCl_4$led to significantly increase in lipid peroxidation and significantly decrease in cytochrome P450 and P450 reductase. The oral administration of the JAE extract significantly inhibited the accumulation of microsomal thiobarbituric acid reactive substance (TBARS) and increased the cytochrome P450 and P450 reductase activity. All these biochemical alterations resulting from $CCl_4$administration were inhibited by the pretreatment with JAE extract. These results suggest that JAE water extract can be useful as a hepatoprotective agent.