View More View Less
  • 1 National Academy of Sciences, Belarus
  • | 2 University of Medical Sciences, Poland
  • | 3 Yanka Kupala State University of Grodno, Belarus
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $752.00

Betulin, a pentacyclic triterpene, possesses antioxidant, anti-inflammatory and hepatoprotective properties. The aim of this study was to evaluate the impact of liver mitochondria in hepatoprotection of betulin using a rat model of alcoholic steatohepatitis induced by ethanol administration (4 g/kg, intragastric) for 8 weeks. The treatment with betulin (50 and 100 mg/kg b.w., intragastric) during this period attenuated the histological signs of steatohepatitis and lowered the serum and liver triglyceride contents, as well as the serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Betulin (100 mg/kg) decreased the liver/body weight ratio and inhibited the increase in the serum levels of TNFα, IL-1β, TGFβ, and hyaluronic acid, demonstrating hepatoprotective, anti-inflammatory, and antifibrotic potential. Betulin also inhibited the formation of superoxide anions in mitochondria and the end-products of lipid peroxidation in liver tissue, the amount of which was significantly increased in ethanol-treated rats. The disturbances in mitochondrial respiration, uncoupling of oxidative phosphorylation and decreasing of mitochondrial complex I, II, and IV activities in rats with steatohepatitis, were reverted by betulin administration. The increased susceptibility of mitochondria to Ca2+-induced permeability transition pore formation in the hepatitis group was improved in rats treated with betulin. In conclusion, betulin, having antioxidant properties, exerts a beneficial effect in the rat model of alcoholic steatohepatitis via prevention of liver mitochondria dysfunction, which may be attributed to the inhibition of mitochondrial permeability transition.

  • 1.

    Akerboom TP , Sies H : Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol. 77, 373382 (1981)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Alavian KN , Beutner G , Lazrove E , Sacchetti S , Park HA , Licznerski P , Li H , Nabili P , Hockensmith K , Graham M , Porter GA Jr , Jonas EA : An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proc. Natl. Acad. Sci. U. S. A. 111, 1058010585 (2014)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Albano E : Alcohol, oxidative stress and free radical damage. Proc. Nutr. Soc. 65, 278290 (2006)

  • 4.

    Bai T , Yang Y , Yao YL , Sun P , Lian LH , Wu YL , Nan JX : Betulin alleviated ethanol-induced alcoholic liver injury via SIRT1/AMPK signaling pathway. Pharmacol. Res. 105, 112 (2016)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Bailey SM , Cunnunham CC : Contribution of mitochondria to oxidative stress associated with alcohol liver disease. Free Radic. Biol. Med. 32, 1116 (2002)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Batandier C , Leverve X , Fontaine E : Opening of the mitochondrial permeability transition pore induces reactive oxygen species production at the level of the respiratory chain complex I. J. Biol. Chem. 279, 1719717204 (2004)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Bernardi P , Lisa DF : The mitochondrial permeability transition pore: molecular nature and role as a target in cardioprotection. J. Mol. Cell Cardiol. 78, 100106 (2015)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Buege JA , Aust SD : Microsomal lipid peroxidation. Methods Enzymol. 52, 302310 (1978)

  • 9.

    Cederbaum AI , Lu Y , Wu D : Role of oxidative stress in alcohol-induced liver injury. Arch. Toxicol. 83, 519548 (2009)

  • 10.

    Ci X , Zhou J , Lv H , Yu Q , Peng L , Hua S : Betulin exhibits anti-inflammatory activity in LPS-stimulated macrophages and endotoxin-shocked mice through an AMPK/AKT/Nrf2-dependent mechanism. Cell Death Dis. 8, е2798 (2017)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Diogo CV , Grattagliano I , Oliveira PJ , Bonfrate L , Portincasa P : Re-wiring the circuit: mitochondria as a pharmacological target in liver disease. Curr. Med. Chem. 18, 54485465 (2011)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Golovach NG , Cheshchevik VT , Lapshina EA , Ilyich TV , Zavodnik IB : Calcium-induced mitochondrial permeability transitions: parameters of Ca2+ ion interactions with mitochondria and effects of oxidative agents. J. Membr. Biol. 250, 225236 (2017)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Johnson D , Lardy HA : Isolation of liver or kidney mitochondria. Methods Enzymol. 10, 9496 (1967)

  • 14.

    Kim M-S , Ong M , Qu X : Optimal management for alcoholic liver disease: conventional medication, natural therapy or combination? World J. Gastroenterol. 22, 823 (2016)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Kowaltowski AJ , Castilho RF , Vercesi AE : Mitochondrial permeability transition and oxidative stress. FEBS Lett. 495, 1215 (2001)

  • 16.

    Li Y , He K , Huang Y , Zheng D , Gao C , Cui L , Jin YH : Betulin induces mitochondrial cytochrome c release associated apoptosis in human cancer cells. Mol. Carcinog. 49, 630640 (2010)

    • Search Google Scholar
    • Export Citation
  • 17.

    Lin W-Y , Lin F-H , Sadhasivam S , Savitha S : Antioxidant effect of betulin on porcine chondrocyte behavior in gelatin/C6S/C4S/HA modified tricopolimer scaffold. Mater. Sci. Eng. 30, 597604 (2010)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Liu J , Liu Y , Mao Q , Klaassen CD : The effects of 10 triterpenoid compounds on experimental liver injury in mice. Fundam. Appl. Toxicol. 22, 3440 (1994)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Louvet A , Mathurin P : Alcoholic liver disease: mechanisms of injury and targeted treatment. Nat. Rev. Gastroenterol. Hepatol. 12, 231242 (2015)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Lowry OH , Rosebrough NJ , Farr AL , Randall RJ : Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265275 (1951)

    • Search Google Scholar
    • Export Citation
  • 21.

    Lukivskaya O , Naruta E , Sadovnichy V , Kirko S , Buko VU : Reversal of experimental ethanol-induced liver steatosis by borage oil. Phytother. Res. 26, 16261631 (2012)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Lukivskaya O , Patsenker E , Buko VU : Protective effect of ursodeoxycholic acid on liver mitochondrial function in rats with alloxan-induced diabetes: link with oxidative stress. Life Sci. 80, 23972402 (2007)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Mathews S , Xu M , Wang H , Bertola A , Gao B : Animals models of gastrointestinal and liver diseases. Animal models of alcohol-induced liver disease: pathophysiology, translational relevance, and challenges. Am. J. Physiol. Gastrointest. Liver Physiol. 306, 819823 (2014)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Müller-Peddinhaus R , Wurl M : The amplified chemiluminescence test to characterize antirheumatic drugs as oxygen radical scavenger. Biochem. Pharmacol. 36, 11251132 (1987)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Nassir F , Ibdah JA : Role of mitochondria in alcoholic liver disease. World J. Gastroenterol. 20, 21362142 (2014)

  • 26.

    Oh SH , Choi JE , Lim SC : Protection of betulin against cadmium-induced apoptosis in hepatoma cells. Toxicology 22, 112 (2006)

  • 27.

    Pastorino JG , Marcineviciute A , Cahill A , Hoek JB : Potentiation by chronic ethanol treatment of the mitochondrial permeability transition. Biochem. Biophys. Res. Commun. 265, 405409 (1999)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Singal AK , Jampana SC , Weinman SA : Antioxidants as therapeutic agents for liver disease. Liver Int. 31, 14321448 (2011)

  • 29.

    Singer TP : Determination of the activity of succinate, NADH, choline, and alpha-glycerophosphate dehydrogenases. Methods Biochem. Anal. 22, 123175 (1974)

    • Search Google Scholar
    • Export Citation
  • 30.

    Smith RA , Hartley RC , Cochemé HM , Murphy MP : Mitochondrial pharmacology. Trends Pharmacol. Sci. 33, 341352 (2012)

  • 31.

    Soica CM , Dehelean CA , Peev C , Aluas M , Zupkó I , Kása P Jr , Alexa E : Physico-chemical comparison of betulinic acid, betulin and birch bark extract and in vitro investigation of their cytotoxic effects towards skin epidermoid carcinoma (A431), breast carcinoma (MCF7) and cervix adenocarcinoma (HeLa) cell lines. Nat. Prod. Res. 26, 968974 (2012)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Szuster-Ciesielska A , Plewka K , Kandefer-Szerszeń M : Betulin, betulinic acid and butein are inhibitors of acetaldehyde-induced activation of liver stellate cells. Pharmacol. Rep. 63, 11091123 (2011)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Tang BL : Sirt1 and the mitochondria. Mol. Cells 39, 8795 (2016)

  • 34.

    Vidya L , Malini MM , Varalakshmi P : Effect of pentacyclic triterpens on oxalate-induced changes in rat erythrocytes. Phamacol. Res. 42, 313316 (2000)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Volynets V , Louis S , Pretz D , Lang L , Ostaff MJ , Wehkamp J , Bischoff SC : Intestinal barrier function and the gut microbiome are differentially affected in mice fed a western-style diet or drinking water supplemented with fructose. J. Nutr. 147(5), 770780 (2017)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Wan Y , Jiang S , Lian LH , Bai T , Cui PH , Sun XT , Jin XJ , Wu YL , Nan JX : Betulinic acid and betulin ameliorate acute ethanol-induced fatty liver via TLR4 and STAT3 in vivo and in vitro. Int. Immunopharmacol. 17, 184190 (2013)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Wikström M , Casey R : The oxidation of exogenous cytochrome c by mitochondria. Resolution of a long-standing controversy. FEBS Lett. 183, 293298 (1985)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Yip WW , Burt AD : Alcoholic liver diseases. Semin. Diagn. Pathol. 23, 149160 (2006)

 

 

The author instruction is available in PDF.

Please, download the file from HERE

 

 

Editor-in-Chief

László ROSIVALL (Semmelweis University, Budapest, Hungary)

Managing Editor

Anna BERHIDI (Semmelweis University, Budapest, Hungary)

Co-Editors

  • Gábor SZÉNÁSI (Semmelweis University, Budapest, Hungary)
  • Ákos KOLLER (Semmelweis University, Budapest, Hungary)
  • Zsolt RADÁK (University of Physical Education, Budapest, Hungary)
  • László LÉNÁRD (University of Pécs, Hungary)
  • Zoltán UNGVÁRI (Semmelweis University, Budapest, Hungary)

Assistant Editors

  • Gabriella DÖRNYEI (Semmelweis University, Budapest, Hungary)
  • Zsuzsanna MIKLÓS (Semmelweis University, Budapest, Hungary)
  • György NÁDASY (Semmelweis University, Budapest, Hungary)

Hungarian Editorial Board

  • György BENEDEK (University of Szeged, Hungary)
  • Zoltán BENYÓ (Semmelweis University, Budapest, Hungary)
  • Mihály BOROS (University of Szeged, Hungary)
  • László CSERNOCH (University of Debrecen, Hungary)
  • Magdolna DANK (Semmelweis University, Budapest, Hungary)
  • László DÉTÁRI (Eötvös Loránd University, Budapest, Hungary)
  • Zoltán GIRICZ (Semmelweis University, Budapest, Hungary and Pharmahungary Group, Szeged, Hungary)
  • Zoltán HANTOS (Semmelweis University, Budapest and University of Szeged, Hungary)
  • László HUNYADI (Semmelweis University, Budapest, Hungary)
  • Gábor JANCSÓ (University of Pécs, Hungary)
  • Zoltán KARÁDI (University of Pecs, Hungary)
  • Miklós PALKOVITS (Semmelweis University, Budapest, Hungary)
  • Gyula PAPP (University of Szeged, Hungary)
  • Gábor PAVLIK (University of Physical Education, Budapest, Hungary)
  • András SPÄT (Semmelweis University, Budapest, Hungary)
  • Gyula SZABÓ (University of Szeged, Hungary)
  • Zoltán SZELÉNYI (University of Pécs, Hungary)
  • Lajos SZOLLÁR (Semmelweis University, Budapest, Hungary)
  • Gyula TELEGDY (MTA-SZTE, Neuroscience Research Group and University of Szeged, Hungary)
  • József TOLDI (MTA-SZTE Neuroscience Research Group and University of Szeged, Hungary)
  • Árpád TÓSAKI (University of Debrecen, Hungary)

International Editorial Board

  • Dragan DJURIC (University of Belgrade, Serbia)
  • Christopher H.  FRY (University of Bristol, UK)
  • Stephen E. GREENWALD (Blizard Institute, Barts and Queen Mary University of London, UK)
  • Osmo Otto Päiviö HÄNNINEN (Finnish Institute for Health and Welfare, Kuopio, Finland)
  • Helmut G. HINGHOFER-SZALKAY (Medical University of Graz, Austria)
  • Tibor HORTOBÁGYI (University of Groningen, Netherlands)
  • George KUNOS (National Institutes of Health, Bethesda, USA)
  • Massoud MAHMOUDIAN (Iran University of Medical Sciences, Tehran, Iran)
  • Tadaaki MANO (Gifu University of Medical Science, Japan)
  • Luis Gabriel NAVAR (Tulane University School of Medicine, New Orleans, USA)
  • Hitoo NISHINO (Nagoya City University, Japan)
  • Ole H. PETERSEN (Cardiff University, UK)
  • Ulrich POHL (German Centre for Cardiovascular Research and Ludwig-Maximilians-University, Planegg, Germany)
  • Andrej A. ROMANOVSKY (University of Arizona, USA)
  • Anwar Ali SIDDIQUI (Aga Khan University, Karachi, Pakistan)
  • Csaba SZABÓ (University of Fribourg, Switzerland)
  • Eric VICAUT (Université de Paris, UMRS 942 INSERM, France)
  • Nico WESTERHOF (Vrije Universiteit Amsterdam, The Netherlands)

 

Editorial Office:
Akadémiai Kiadó Zrt.
Prielle Kornélia u. 21–35, H-1117 Budapest, Hungary

Editorial Correspondence:
Physiology International
Semmelweis University, Faculty of Medicine Institute of Pathophysiology
Nagyvárad tér 4, H-1089 Budapest, Hungary
Phone/Fax: +36-1-2100-100
E-mail: pi@semmelweis-univ.hu

Indexing and Abstracting Services:

  • Biological Abstracts
  • BIOSIS Previews
  • CAB Abstracts
  • EMBASE/Excerpta Medica
  • Global Health
  • Index Copernicus
  • Index Medicus
  • Medline
  • Referativnyi Zhurnal
  • SCOPUS
  • Social Science Citation Index

 

 

2020  
Total Cites 245
WoS
Journal
Impact Factor
2,090
Rank by Physiology 62/81 (Q4)
Impact Factor  
Impact Factor 1,866
without
Journal Self Cites
5 Year 1,703
Impact Factor
Journal  0,51
Citation Indicator  
Rank by Journal  Physiology 67/84 (Q4)
Citation Indicator   
Citable 42
Items
Total 42
Articles
Total 0
Reviews
Scimago 29
H-index
Scimago 0,417
Journal Rank
Scimago Physiology (medical) Q3
Quartile Score  
Scopus 270/1140=1,9
Scite Score  
Scopus Physiology (medical) 71/98 (Q3)
Scite Score Rank  
Scopus 0,528
SNIP  
Days from  172
submission  
to acceptance  
Days from  106
acceptance  
to publication  

2019  
Total Cites
WoS
137
Impact Factor 1,410
Impact Factor
without
Journal Self Cites
1,361
5 Year
Impact Factor
1,221
Immediacy
Index
0,294
Citable
Items
34
Total
Articles
33
Total
Reviews
1
Cited
Half-Life
2,1
Citing
Half-Life
9,3
Eigenfactor
Score
0,00028
Article Influence
Score
0,215
% Articles
in
Citable Items
97,06
Normalized
Eigenfactor
0,03445
Average
IF
Percentile
12,963
Scimago
H-index
27
Scimago
Journal Rank
0,267
Scopus
Scite Score
235/157=1,5
Scopus
Scite Score Rank
Physiology (medical) 73/99 (Q3)
Scopus
SNIP
0,38

 

Physiology International
Publication Model Hybrid
Submission Fee none
Article Processing Charge 1100 EUR/article
Printed Color Illustrations 40 EUR (or 10 000 HUF) + VAT / piece
Regional discounts on country of the funding agency World Bank Lower-middle-income economies: 50%
World Bank Low-income economies: 100%
Further Discounts Editorial Board / Advisory Board members: 50%
Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100%
Subscription fee 2021 Online subsscription: 632 EUR / 788 USD 
Print + online subscription: 736 EUR / 920 USD
Subscription fee 2022 Online subsscription: 644 EUR / 806 USD
Print + online subscription: 752 EUR / 942 USD
Subscription Information Online subscribers are entitled access to all back issues published by Akadémiai Kiadó for each title for the duration of the subscription, as well as Online First content for the subscribed content.
Purchase per Title Individual articles are sold on the displayed price.

Physiology International
Language English
Size B5
Year of
Foundation
2006 (1950)
Publication
Programme
2021 Volume 108
Volumes
per Year
1
Issues
per Year
4
Founder Magyar Tudományos Akadémia
Founder's
Address
H-1051 Budapest, Hungary, Széchenyi István tér 9.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2498-602X (Print)
ISSN 2677-0164 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Jun 2021 22 0 0
Jul 2021 13 0 0
Aug 2021 18 0 0
Sep 2021 8 0 0
Oct 2021 22 0 0
Nov 2021 29 0 0
Dec 2021 8 0 0