• Title/Summary/Keyword: Human liver

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A Cholesterol Biosynthesis Inhibitor from Rhizopus oryzae

  • Kim, Hyun-Jung;Yim, Soon-Ho;Lee, Ik-Soo
    • Archives of Pharmacal Research
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    • v.27 no.6
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    • pp.624-627
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    • 2004
  • A bile acid derivative, methyl chalate (1), was isolated from EtOAc extract of the fungus Rhizopus oryzae as a cholesterol biosynthesis inhibitor. It showed moderate inhibitory activity on cholesterol biosynthesis in human Chang liver cells. Compound 1 exhibited inhibitory effect on the later step of cholesterol biosynthesis, indicating that its action mode is different from that of statins that act on the HMG-CoA reductase.

Reabsorption of Neutral Amino Acids Mediated by Amino Acid Transporter LAT2 and TAT1 in The Basolateral Membrane of Proximal Tubule

  • Park Sun Young;Kim Jong-Keun;Kim In Jin;Choi Bong Kyu;Jung Kyu Yong;Lee Seoul;Park Kyung Jin;Chairoungdua Arthit;Kanai Yoshikatsu;Endou Hitoshi;Kim Do Kyung
    • Archives of Pharmacal Research
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    • v.28 no.4
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    • pp.421-432
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    • 2005
  • In order to understand the renal reabsorption mechanism of neutral amino acids via amino acid transporters, we have isolated human L-type amino acid transporter 2 (hLAT2) and human T-type amino acid transporter 1 (hTAT1) in human, then, we have examined and compared the gene structures, the functional characterizations and the localization in human kidney. Northern blot analysis showed that hLAT2 mRNA was expressed at high levels in the heart, brain, placenta, kidney, spleen, prostate, testis, ovary, lymph node and the fetal liver. The hTAT1 mRNA was detected at high levels in the heart, placenta, liver, skeletal muscle, kidney, pancreas, spleen, thymus and prostate. Immunohistochemical analysis on the human kidney revealed that the hLAT2 and hTAT1 proteins coexist in the basolateral membrane of the renal proximal tubules. The hLAT2 transports all neutral amino acids and hTAT1 transports aromatic amino acids. The basolateral location of the hLAT2 and hTAT1 proteins in the renal proximal tubule as well as the amino acid transport activity of hLAT2 and hTAT1 suggests that these transporters contribute to the renal reabsorption of neutral and aromatic amino acids in the basolateral domain of epithelial proximal tubule cells, respectively. Therefore, LAT2 and TAT1 play essential roles in the reabsorption of neutral amino acids from the epithelial cells to the blood stream in the kidney. Because LAT2 and TAT1 are essential to the efficient absorption of neutral amino acids from the kidney, their defects might be involved in the pathogenesis of disorders caused by a disruption in amino acid absorption such as blue diaper syndrome.

Direct Conversion of L-Selenomethionine into Methylselenol by Human Cystathionine ${\gamma}$-Lyase (인간 Cystathionine ${\gamma}$-Lyase에 의한 Selenomethionine의 Methylselenol로의 직접분해)

  • Cho, Hyun-Nam;Jhee, Kwang-Hwan
    • Microbiology and Biotechnology Letters
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    • v.42 no.1
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    • pp.11-17
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    • 2014
  • Selenium is an essential trace element for mammals, but it is very toxic. Therefore, the control of selenium concentrations should be precisely and effectively monitored. Selenium is naturally obtained through foods and seleno-L-methionine (LSeMet) is a major form of selenium. It has been reported that L-SeMet is only converted into Se-adenosyl-L-SeMet. However, a recent study suggested that L-SeMet was directly metabolized into methylselenol ($CH_3SeH$) in mouse liver extract by the reaction of cystathionine ${\gamma}$-lyase (CGL). The canonical reaction of CGL was known to catalyze the cleavage of L-cystathionine to L-cysteine, ${\alpha}$-ketobutyrate and $NH_3$. In the present study, we found that L-SeMet could be directly converted to $CH_3SeH$ using purified homogenous human CGL instead of mouse liver cytosol. Authentic $CH_3SeH$ was prepared by reduction of dimethyldiselenide with sodium tetrahydroborate. The gaseous product of the enzymatic reaction with L-SeMet was analyzed by GC/MS spectrometry. The GC/MS data was identical to that of authentic dinitrophenyl selenoether. We also analyzed the kinetic parameters for the formation of $CH_3SeH$ from L-SeMet by human and mouse CGL. These results suggest that human CGL is a critical enzyme which is responsible for L-SeMet metabolism.

Latest Study on the Assignment of the Eight Trigrams in Human Body (팔괘(八卦)의 인체 배속(配屬)에 대한 새로운 연구 - (하도 락서)河圖 洛書를 중심으로-)

  • Shin, Soon-Shik;Kim, Hun;Kim, Yi-Soon;Kim, Gyeon-Cheol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1447-1450
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    • 2006
  • To study on the assignment of the eight trigrams (八卦) in human body being based on based the number of HADO(河圖)-NAGSEO(洛書). Being based on the number of HADO(河圖)-NAGSEO(洛書) and the BEOK-HEE's diagram of eight trigrams order(伏羲次序圖), human being organ (five-Jang organs (liver, heart, spleen, lung and kidney), five organs (ear, eye, mouth and nose), provisional namely six entera for the process on intake, digestion, excretion of food (mouth, stomach, small intestine, large intestine, rectum, anus) are assigned eight trigrams (八卦). Eight trigrams(八卦) are attached to the based on the number HADO(河圖)-NAGSEO(洛書): 1-GEON(乾), 2-TAE(兌), 3-LEE(離), 4-JIN(震), 9-SON(巽), 6-GAM(坎), 7-GAN(艮), 8-GON(坤). And (八卦) are attached to the human being organs (five-Jang organs (live, heart, spleen, lung and kidney), five organs (ear, eye, mouth, nose, anus) : 1-GEON(乾)-left lung-left nose, 6-GAM(坎)-right kidney-right ear, 7-GAN(艮)-left heart-anus, 8-GON(坤)-right liver-right ear. Eight trigrams(八卦) are attached to the provisional namely six entera for the process on intake, digestion, excretion of food : the air(GEON 乾), the month(TAE 兌), the stomach(LEE 離), the small intestine(JIN 震), the large intestine(Son 巽), the rectum(GAM 坎), the anus(GAN 艮), the excrements(GON 坤). The BEOK-HEE's diagram of eight trigrams order(伏羲次序圖) means immutable order naturally. The process of the human being organs( five-Jang organs, five organs and six entera's digestion) is also unchangeable in region and program. Therefore we can set up the five-Jang organs, five organs and the process of six entera's digestion as the category of observation on the basis of BEOK-HEE's diagram of eight trigrams order(伏羲次序圖), and then we can arrange eight trigrams (八卦) on the five-Jang organs, five organs and the process of six entera's digestion.

The Carcinogenic Liver Fluke Opisthorchis viverrini is a Reservoir for Species of Helicobacter

  • Deenonpoe, Raksawan;Chomvarin, Chariya;Pairojkul, Chawalit;Chamgramol, Yaowalux;Loukas, Alex;Brindley, Paul J;Sripa, Banchob
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1751-1758
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    • 2015
  • There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms were collected and the presence of species of Helicobacter determined by PCR-based approaches. In addition, O. viverrini worms were cultured in vitro with and without ABx for four weeks, after which the presence of Helicobacter spp. was determined. In situ localization of H. pylori and Helicobacter-like species was performed using a combination of histochemistry and immunohistochemistry. The prevalence of H. pylori infection in O. viverrini-infected hamsters was significantly higher than that of O. viverrini-uninfected hamsters ($p{\leq}0.001$). Interestingly, O. viverrini-infected hamsters treated with ABx and PZQ (to remove the flukes) had a significantly lower frequency of H. pylori than either O. viverr-iniinfected hamsters treated only with ABx or O. viverrini-infected hamsters, respectively ($p{\leq}0.001$). Quantitative RT-PCR strongly confirmed the correlation between intensity H. pylori infection and the presence of liver fluke infection. In vitro, H. pylori could be detected in the O. viverrini worms cultured with ABx over four weeks. In situ localization revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings indicate that the liver fluke O. viverrini in the biliary tree of the hamsters harbors H. pylori and Helicobacter-like bacteria. Accordingly, the association between O. viverrini and H. pylori may be an obligatory mutualism.

Hepatoprotective effect of Paeoniae radix via Nrf2 activation (Nrf2 활성화(活性化)를 통한 작약(芍藥)의 간보호효과(肝保護效果))

  • Lee, Soo Hwan;Jung, Ji Yun;Park, Sang Mi;Jegal, Kyung Hwan;Byun, Sung Hui;Cho, Il Je;Kim, Sang Chan;Kim, Kwang Joong;Kim, Young Woo
    • The Korea Journal of Herbology
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    • v.31 no.1
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    • pp.33-40
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    • 2016
  • Objectives : Liver is one of the largest organs in the human, and has a function of detoxification and energy sensing to prevent severe disease. Paeoniae radix has been used to treat a variety of liver diseases such as hepatitis and chronic hepatic failure. Although P. radix has been used as an medicinal herb for a long time, the effects of P. radix on severe oxidative stress and its action mechanism on the liver was not clearly verified.Methods : This study investigated the protective effects of P. radix extract (PRE), and the underlying mechanism of its action in the liver. tert-butyl hydroperoxide (t-BHP) and carbon tetrachlroride (CCl4) were used to induce oxidative stress in the HepG2 hepatocyte cell line and Sprague-Dawley rats, respectively.Results : t-BHP significantly induced cell death and ROS production in HepG2 cell, as indicated by MTT and FACS analysis. However, pretreatment of PRE inhibited a decrease in cell viability and H2O2 production in the HepG2 cells. PRE also blocked the ability of t-BHP to damage in mitochondrial membrane transition. More importantly, PRE induced Nrf2 activation and antioxidant Phase II enzyme, which may have a role in the effects of PRE. In mice, PRE inhibited the liver damage induced by CCl4.Conclusions : PRE inhibited oxidative stress and hepatic damages as mediated with Nrf2 activation. This study unveil, in part, the effect and mechanism of old medicinal herb, P. radix.

Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study

  • Peter, Aniekan Imo;Naidu, Edwin CS;Akang, Edidiong;Ogedengbe, Oluwatosin O;Offor, Ugochukwu;Rambharose, Sanjeev;Kalhapure, Rahul;Chuturgoon, Anil;Govender, Thirumala;Azu, Onyemaechi O
    • Toxicological Research
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    • v.34 no.3
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    • pp.221-229
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    • 2018
  • Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.