Abstract

This study aimed to assess the preventive effects of Camellia sinensis (green tea) leaf aqueous extract and epicatechin and to scrutinize their possible mechanisms of action in doxorubicin-induced liver injury. Phytochemical screening of Camellia sinensis aqueous extract was performed by LC/ESI-MS/MS that revealed the presence of epicatechin and other polyphenols. Male Wistar rats were intraperitoneally injected with doxorubicin (4 mg/kg/week) and were orally treated with Camellia sinensis aqueous extract (200 mg/kg) or epicatechin (25 mg/kg) every other day for 6 weeks. The treatments of doxorubicin-injected rats with the extract and epicatechin resulted in a marked amelioration of the deteriorated effects on albumin, AFP and total bilirubin levels as well as ALT, AST, ALP and GGT activities. The treatments also alleviated the altered serum TNF-α and IL-4, liver LPO and GSH levels as well as liver SOD, GPx and GST activities. In association, the expression of liver NF-κB, COX-2, p53 and caspase-3 was remarkably decreased, the expression of Bcl-2 was significantly increased, and the liver histological architecture were remarkably amended by treatments. Camellia sinensis aqueous extract and epicatechin may have effective chemopreventive potentials against doxorubicin-induced hepatotoxicity via reinforcement of antioxidant defense system and attenuation of the inflammatory and apoptotic effects.

Highlights

  • The liver, as vital organ, performs an array of complex functions coordinating metabolic, immunologic, and detoxification processes (Sendensky and Dufour, 2011)

  • Phytochemical screening of C. sinensis aqueous extract was performed by liquid chromatography electrospray ionization tandem mass spectrometry that revealed the presence of epicatechin and other polyphenols

  • The treatment of Dox-administered rats with epicatechin caused a significant decrease of the serum AFP (p < 0.05) levels recording percentage decrease −67.54% while it produced a non-significant decrease of serum total bilirubin level recording percentage decrease −5.26%

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Summary

Introduction

The liver, as vital organ, performs an array of complex functions coordinating metabolic, immunologic, and detoxification processes (Sendensky and Dufour, 2011). Dox is an effective anti-cancer agent, its use is significantly limited owing to its side effects and toxicity (Ahmed et al, 2019). This Dox toxicity often affects many organs such as liver, heart, brain, kidneys, and testes, thereby limiting its clinical application (Tacar et al, 2013; Trivedi et al, 2011). Mitochondria were suggested to be one of the main targets of Dox which produces its action through mitochondria-mediated apoptosis leading to modifications in mitochondrial membranes; this, in turn, results in alterations in oxidative phosphorylation and respiratory chain complexes in the mitochondria (Trivedi et al, 2011). Dox significantly deteriorates energy-signaling and -transducing systems like

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