Anthocyanins Protect Hepatocytes against CCl<sub>4</sub>-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells
This study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from <i>Vaccinim myrtillus</i> (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl<sub>4</sub> (3 mL/kg, i.p.). The preventive treatment of the bilberry e...
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2019-10-01
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author | Dejan Popović Gordana Kocić Vuka Katić Aleksandra Zarubica Ljubinka Janković Veličković Vanja P. Ničković Andrija Jović Andrej Veljković Vladimir Petrović Violeta Rakić Zorica Jović Nataša Poklar Ulrih Danka Sokolović Marko Stojanović Marko Stanković Goran Radenković Gordana R. Nikolić Аzra Lukač Aleksandar Milosavljević Dušan Sokolović |
author_facet | Dejan Popović Gordana Kocić Vuka Katić Aleksandra Zarubica Ljubinka Janković Veličković Vanja P. Ničković Andrija Jović Andrej Veljković Vladimir Petrović Violeta Rakić Zorica Jović Nataša Poklar Ulrih Danka Sokolović Marko Stojanović Marko Stanković Goran Radenković Gordana R. Nikolić Аzra Lukač Aleksandar Milosavljević Dušan Sokolović |
author_sort | Dejan Popović |
collection | DOAJ |
description | This study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from <i>Vaccinim myrtillus</i> (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl<sub>4</sub> (3 mL/kg, i.p.). The preventive treatment of the bilberry extract (200 mg anthocyanins/kg, orally, 7 days) prior to the exposure to the CCl<sub>4</sub> resulted in an evident decrease in markers of liver damage (glutamate dehydrogenase, sorbitol dehydrogenase, malate dehydrogenase), and reduced pro-oxidative (conjugated dienes, lipid hydroperoxide, thiobarbituric acid reactive substances, advanced oxidation protein products, NADPH oxidase, hydrogen peroxide, oxidized glutathione), and pro-inflammatory markers (tumor necrosis factor-alpha, interleukin-6, nitrite, myeloperoxidase, inducible nitric oxide synthase, cyclooxygenase-2, CD68, lipocalin-2), and also caused a significant decrease in the dissipation of the liver antioxidative defence capacities (reduced glutathione, glutathione S-transferase, and quinone reductase) in comparison to the results detected in the animals treated with CCl<sub>4</sub> exclusively. The administration of the anthocyanins prevented the arginine metabolism’s diversion towards the citrulline, decreased the catabolism of polyamines (the activity of putrescine oxidase and spermine oxidase), and significantly reduced the excessive activation and hyperplasia of the Kupffer cells. There was also an absence of necrosis, in regard to the toxic effect of CCl<sub>4</sub> alone. The hepatoprotective mechanisms of bilberry extract are based on the inhibition of pro-oxidative mediators, strong anti-inflammatory properties, inducing of hepatic phase II antioxidant enzymes (glutathione S-transferase, quinone reductase) and reduced glutathione, hypoplasia of Kupffer cells, and a decrease in the catabolism of polyamines. |
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spelling | doaj.art-b6212ff7d7ae49a49f3c6ac5ce8c9b5b2023-09-02T23:25:36ZengMDPI AGAntioxidants2076-39212019-10-0181045110.3390/antiox8100451antiox8100451Anthocyanins Protect Hepatocytes against CCl<sub>4</sub>-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer CellsDejan Popović0Gordana Kocić1Vuka Katić2Aleksandra Zarubica3Ljubinka Janković Veličković4Vanja P. Ničković5Andrija Jović6Andrej Veljković7Vladimir Petrović8Violeta Rakić9Zorica Jović10Nataša Poklar Ulrih11Danka Sokolović12Marko Stojanović13Marko Stanković14Goran Radenković15Gordana R. Nikolić16Аzra Lukač17Aleksandar Milosavljević18Dušan Sokolović19Department of Biochemistry, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaDepartment of Biochemistry, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaDepartment of Pathology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaDepartment of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, SerbiaDepartment of Pathology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaClinical-Hospital Center Priština, 38205 Gračanica, SerbiaClinic of Skin and Venereal Diseases, Clinical Center of Niš, Bulevar dr Zorana Đinđića 48, 18000 Niš, SerbiaDepartment of Biochemistry, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaDepartment of Histology and Embryology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaCollege of Agriculture and Food Technology, Ćirila i Metodija 1, 18400 Prokuplje, SerbiaDepartment of Pharmacology and Toxicology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaDepartment of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, SloveniaInstitute for Blood Transfusion in Nis, Bulevar dr Zorana Đinđića 48, 18000 Niš, SerbiaFaculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaFaculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaDepartment of Histology and Embryology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaMedical Faculty, University of Priština, 38220 Kosovska Mitrovica, SerbiaHealth Center Rožaje, 84310 Rožaje, MontenegroFaculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaDepartment of Biochemistry, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, SerbiaThis study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from <i>Vaccinim myrtillus</i> (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl<sub>4</sub> (3 mL/kg, i.p.). The preventive treatment of the bilberry extract (200 mg anthocyanins/kg, orally, 7 days) prior to the exposure to the CCl<sub>4</sub> resulted in an evident decrease in markers of liver damage (glutamate dehydrogenase, sorbitol dehydrogenase, malate dehydrogenase), and reduced pro-oxidative (conjugated dienes, lipid hydroperoxide, thiobarbituric acid reactive substances, advanced oxidation protein products, NADPH oxidase, hydrogen peroxide, oxidized glutathione), and pro-inflammatory markers (tumor necrosis factor-alpha, interleukin-6, nitrite, myeloperoxidase, inducible nitric oxide synthase, cyclooxygenase-2, CD68, lipocalin-2), and also caused a significant decrease in the dissipation of the liver antioxidative defence capacities (reduced glutathione, glutathione S-transferase, and quinone reductase) in comparison to the results detected in the animals treated with CCl<sub>4</sub> exclusively. The administration of the anthocyanins prevented the arginine metabolism’s diversion towards the citrulline, decreased the catabolism of polyamines (the activity of putrescine oxidase and spermine oxidase), and significantly reduced the excessive activation and hyperplasia of the Kupffer cells. There was also an absence of necrosis, in regard to the toxic effect of CCl<sub>4</sub> alone. The hepatoprotective mechanisms of bilberry extract are based on the inhibition of pro-oxidative mediators, strong anti-inflammatory properties, inducing of hepatic phase II antioxidant enzymes (glutathione S-transferase, quinone reductase) and reduced glutathione, hypoplasia of Kupffer cells, and a decrease in the catabolism of polyamines.https://www.mdpi.com/2076-3921/8/10/451carbon tetrachlorideanthocyaninsanti-inflammatory effectskupffer cellslipocalin-2polyamine catabolism |
spellingShingle | Dejan Popović Gordana Kocić Vuka Katić Aleksandra Zarubica Ljubinka Janković Veličković Vanja P. Ničković Andrija Jović Andrej Veljković Vladimir Petrović Violeta Rakić Zorica Jović Nataša Poklar Ulrih Danka Sokolović Marko Stojanović Marko Stanković Goran Radenković Gordana R. Nikolić Аzra Lukač Aleksandar Milosavljević Dušan Sokolović Anthocyanins Protect Hepatocytes against CCl<sub>4</sub>-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells Antioxidants carbon tetrachloride anthocyanins anti-inflammatory effects kupffer cells lipocalin-2 polyamine catabolism |
title | Anthocyanins Protect Hepatocytes against CCl<sub>4</sub>-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells |
title_full | Anthocyanins Protect Hepatocytes against CCl<sub>4</sub>-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells |
title_fullStr | Anthocyanins Protect Hepatocytes against CCl<sub>4</sub>-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells |
title_full_unstemmed | Anthocyanins Protect Hepatocytes against CCl<sub>4</sub>-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells |
title_short | Anthocyanins Protect Hepatocytes against CCl<sub>4</sub>-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells |
title_sort | anthocyanins protect hepatocytes against ccl sub 4 sub induced acute liver injury in rats by inhibiting pro inflammatory mediators polyamine catabolism lipocalin 2 and excessive proliferation of kupffer cells |
topic | carbon tetrachloride anthocyanins anti-inflammatory effects kupffer cells lipocalin-2 polyamine catabolism |
url | https://www.mdpi.com/2076-3921/8/10/451 |
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