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Open AccessArticle

Anthocyanins Protect Hepatocytes against CCl4-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells

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Department of Biochemistry, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
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Department of Pathology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
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Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia
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Clinical-Hospital Center Priština, 38205 Gračanica, Serbia
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Clinic of Skin and Venereal Diseases, Clinical Center of Niš, Bulevar dr Zorana Đinđića 48, 18000 Niš, Serbia
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Department of Histology and Embryology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
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College of Agriculture and Food Technology, Ćirila i Metodija 1, 18400 Prokuplje, Serbia
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Department of Pharmacology and Toxicology, Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
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Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, Slovenia
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Institute for Blood Transfusion in Nis, Bulevar dr Zorana Đinđića 48, 18000 Niš, Serbia
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Faculty of Medicine, University of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia
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Medical Faculty, University of Priština, 38220 Kosovska Mitrovica, Serbia
13
Health Center Rožaje, 84310 Rožaje, Montenegro
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(10), 451; https://doi.org/10.3390/antiox8100451
Received: 25 July 2019 / Revised: 29 August 2019 / Accepted: 31 August 2019 / Published: 4 October 2019
(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)
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. View Full-Text
Keywords: carbon tetrachloride; anthocyanins; anti-inflammatory effects; kupffer cells; lipocalin-2; polyamine catabolism carbon tetrachloride; anthocyanins; anti-inflammatory effects; kupffer cells; lipocalin-2; polyamine catabolism
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Popović, D.; Kocić, G.; Katić, V.; Zarubica, A.; Janković Veličković, L.; Ničković, V.P.; Jović, A.; Veljković, A.; Petrović, V.; Rakić, V.; Jović, Z.; Poklar Ulrih, N.; Sokolović, D.; Stojanović, M.; Stanković, M.; Radenković, G.; Nikolić, G.R.; Lukač, А.; Milosavljević, A.; Sokolović, D. Anthocyanins Protect Hepatocytes against CCl4-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells. Antioxidants 2019, 8, 451.

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