Anthocyanin-Rich Extract of Red Cabbage Attenuates Advanced Alcohol Hepatotoxicity in Rats in Association with Mitochondrial Activity Modulation

Abstract

Aim: The liver is the main target for alcohol-induced injury. The aims of this work were to carry out further research into the mechanisms of liver damage induced by long-term administration of high-dose ethanol to rats and to evaluate the hepatoprotective potential of red cabbage (Brassica oleracea var. capitata f. rubra) anthocyanins (RCE). Material/Methods: Male albino Wistar rats were divided into four groups. Group 1 was the control. Groups 2 through 4 received ethanol (4 g/kg body weight, 8 weeks). Group 3 received 11 mg RCE/kg and Group 4 received 22 mg RCE/kg. Dry lyophilised RCE was prepared from fresh red cabbage and analysed. We then evaluated the liver histology, mitochondrial respiration, and biochemical and immunological parameters in these groups of rats. Results: The rat intoxication caused steatohepatitis characterised by macro- and microvesicular steatosis, ballooning and fatty liver dystrophies, lymphocytic infiltration, neutral lipid accumulation, and elevations of the serum activities of the liver injury marker enzymes. The treatment of alcohol-administered rats with RCE (mainly, cyanidin-3-diglucoside-5-glucoside, cyanidin-3-coumaroylrutinoside-5-hexoside, cyanidin-3-feruloylrutinoside-5-hexoside, delphinidin-3-feruloylrutinoside-hexoside) dose-dependently alleviated these pathological changes: The sizes of hepatocyte lipid vacuoles and the inflammatory signs were decreased, and the levels of the rat serum biochemical markers of liver injury, proinflammatory cytokines TNFα and IL-6, and the adipokine leptin (and not TGFβ) were significantly reversed. The RCE administration during intoxication completely recovered the changed liver mitochondria respiration rates and the ADP/O coefficient, as well as the phagocytic index and neutrophil metabolic activity in the blood. In experiments in vitro, RCE (13.6 μg/ml) modulated the respiratory parameters of isolated rat liver mitochondria, dissipated mitochondrial membrane potential, and inhibited the Ca2+-induced mitochondrial permeability transition. Conclusion: The red cabbage anthocyanins could be useful for treatment of alcoholic liver injury due to their Ca2+-ionophoric/protonophoric activity, influence on Ca2+ homeostasis, and improving mitochondrial functions and inflammatory status.