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
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
Affiliations
Dejan Popović
Department of Biochemistry, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Gordana Kocić
Department of Biochemistry, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Vuka Katić
Department of Pathology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Aleksandra Zarubica
Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia
Ljubinka Janković Veličković
Department of Pathology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Vanja P. Ničković
Clinical-Hospital Center Priština, 38205 Gračanica, Serbia
Andrija Jović
Clinic of Skin and Venereal Diseases, Clinical Center of Niš, Bulevar dr Zorana Đinđića 48, 18000 Niš, Serbia
Andrej Veljković
Department of Biochemistry, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Vladimir Petrović
Department of Histology and Embryology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Violeta Rakić
College of Agriculture and Food Technology, Ćirila i Metodija 1, 18400 Prokuplje, Serbia
Zorica Jović
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Nataša Poklar Ulrih
Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, Slovenia
Danka Sokolović
Institute for Blood Transfusion in Nis, Bulevar dr Zorana Đinđića 48, 18000 Niš, Serbia
Marko Stojanović
Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Marko Stanković
Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Goran Radenković
Department of Histology and Embryology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Gordana R. Nikolić
Medical Faculty, University of Priština, 38220 Kosovska Mitrovica, Serbia
Аzra Lukač
Health Center Rožaje, 84310 Rožaje, Montenegro
Aleksandar Milosavljević
Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
Dušan Sokolović
Department of Biochemistry, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
This study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from Vaccinim myrtillus (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl4 (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 CCl4 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 CCl4 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 CCl4 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.
