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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/8/10/451
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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&#8217;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&#8217;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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