Hepatoprotective Effect of Mixture of Dipropyl Polysulfides in Concanavalin A-Induced Hepatitis.

Dragana Arsenijevic,Nebojsa Arsenijevic,Dragan Manojlovic,Marija Pergal,Danilo Vojvodic,Igor Kodranov,Olga Cvetkovic,Marija Milovanovic,Aleksandar Arsenijevic,Elizabeta Ristanovic,Jelena Milovanovic,Bojana Stojanovic,Milos Simic

doi:10.3390/nu13031022

Abstract

The main biologically active components of plants belonging to the genus Allium, responsible for their biological activities, including anti-inflammatory, antioxidant and immunomodulatory, are organosulfur compounds. The aim of this study was to synthetize the mixture of dipropyl polysulfides (DPPS) and to test their biological activity in acute hepatitis. C57BL/6 mice were administered orally with DPPS 6 h before intravenous injection of Concanavalin A (ConA). Liver inflammation, necrosis and hepatocytes apoptosis were determined by histological analyses. Cytokines in liver tissue were determined by ELISA, expression of adhesive molecules and enzymes by RT PCR, while liver mononuclear cells were analyzed by flow cytometry. DPPS pretreatment significantly attenuated liver inflammation and injury, as evidenced by biochemical and histopathological observations. In DPPS-pretreated mice, messenger RNA levels of adhesion molecules and NADPH oxidase complex were significantly reduced, while the expression of SOD enzymes was enhanced. DPPS pretreatment decreased protein level of inflammatory cytokines and increased percentage of T regulatory cells in the livers of ConA mice. DPPS showed hepatoprotective effects in ConA-induced hepatitis, characterized by attenuation of inflammation and affection of Th17/Treg balance in favor of T regulatory cells and implicating potential therapeutic usage of DPPS mixture in inflammatory liver diseases.

Highlights

Liver inflammatory diseases, caused by viral infections, alcohol abuse, drugs, or autoimmune reactions, are still one of the major threats to human health
We investigated the effect of the mixture of newly synthetized dipropyl polysulfides, known as biologically active ingredients of garlic [21], on ConAinduced hepatitis
The results showed that dipropyl polysulfides (DPPS) pretreatment, 6 h prior to Concanavalin A (ConA) injection, markedly downregulated serum ALT levels and inhibited hepatocyte apoptosis/necrosis

Summary

Introduction

Liver inflammatory diseases, caused by viral infections, alcohol abuse, drugs, or autoimmune reactions, are still one of the major threats to human health. ConA-induced hepatitis in mice is primarily mediated by T cells and has been widely used as a model for acute or fulminant immune-mediated liver diseases [1,2]. ConA binds to liver sinusoidal endothelial cells (SEC) and induces their damage [3]. Damaged SEC allow ConA to bind Kupffer cells, which induce polyclonal activation of T cells. Production of inflammatory cytokines and hepatocytes death in ConA-induced hepatitis is enhanced by superoxide anions released by stimulated Kupffer cells and hepatocytes [9]

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