Assessment of Hepatoprotective Effect of Chokeberry Juice in Rats Treated Chronically with Carbon Tetrachloride.

Hanna Piotrowska-Kempisty,Monika Kurpik,Teresa Adamska,Małgorzata Ewertowska,Jadwiga Jodynis-Liebert,Małgorzata Kujawska,Michał Nowicki,Jan Oszmiański

doi:10.3390/molecules25061268

Abstract

The aim of this study was to compare the protective effects of chokeberry juice and silymarin against chemical-induced liver fibrosis in rats. Liver fibrosis was induced by CCl4 administered two days a week for six weeks. Two groups of rats were co-treated with chokeberry juice, 10 mL/kg/day. or silymarin as a positive control, 100 mg/kg/day for six weeks. Hepatic lipid peroxidation was suppressed by 50% and the activity of hepatic antioxidant enzymes was increased by 19%–173% in rats co-treated with CCl4 and substances tested as compared to rats administered CCl4 alone. Hepatic hydroxyproline was decreased by 24% only in rats treated with silymarin. The messenger RNA (mRNA) expression levels of fibrosis-related molecules, procollagen I, α-SMA, TIMP-1, TGFβ, and TNFα, which were significantly increased in the liver of CCl4-treated rats, were not modulated by substances tested. Histological evaluation revealed a slight protective effect of silymarin against fibrosis. However, in CCl4 + chokeberry-treated rats, the density of vacuolated hepatocytes was significantly lower than that in silymarin administered animals. Chokeberry juice did not demonstrate an antifibrotic effect in the applied experimental model of fibrosis, and the effect of the known antifibrotic agent, silymarin, was very limited.

Highlights

Fibrosis progressing to cirrhosis is a major complication of various chronic liver diseases such as alcoholic, viral, and autoimmune hepatitis
Liver macrophages (Kupffer cells) and other inflammatory cells are activated, which leads to the production of cytokines including the profibrogenic cytokines such as platelet-derived growth factor (PDGF)
The protective effect of silymarin on antioxidant enzymes in chronic liver injury was not extensively reported in the literature except for our previous work in which silymarin was shown to attenuate the decrease in superoxide dismutase (SOD), CAT Glutathione peroxidase (GPx), and Glutathione reductase (GR)

Summary

Introduction

Fibrosis progressing to cirrhosis is a major complication of various chronic liver diseases such as alcoholic, viral, and autoimmune hepatitis. Morbidity and mortality due to advanced cirrhosis are comparable to those of malignancies [1]. Hepatic fibrosis results from the disequilibrium between synthesis and degradation of extracellular matrix (ECM) components. Liver macrophages (Kupffer cells) and other inflammatory cells are activated, which leads to the production of cytokines including the profibrogenic cytokines such as platelet-derived growth factor (PDGF). Transforming growth factor β (TGFβ), which can stimulate the hepatic stellate cells (HSCs) and fibroblasts. The activation of HSCs by cytokines and other mediators is considered as a central event in the pathophysiology of liver fibrosis. Activated HSCs/myofibroblasts are the major source of ECM molecules, which comprise collagens, non-collagenous glycoproteins, proteoglycans, and glycoaminoglycans [2]

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