Therapeutic dose of green tea extract provokes liver damage and exacerbates paracetamol-induced hepatotoxicity in rats through oxidative stress and caspase 3-dependent apoptosis

Abstract

Green tea extract (GTE) is considered to be endowed with countless healthful properties. Nevertheless, data concerning the hepatoprotective activities of GTE and its utilization as a therapeutic intervention for paracetamol (APAP) overdose are conflicting and intriguing. The present study was undertaken to address the effect of therapeutic dose of GTE on the liver, evaluate the potential hepatoprotection of GTE against APAP-induced hepatotoxicity, asses the regenerative capacity of the liver after discontinuation of treatments, and explore the mechanisms underlying these effects. Adult male albino rats were divided into six groups (n=9 each): (1) control, (2) APAP (2g/kg, orally for one week), (3) GTE (8.5mg/kg, orally for one month), (4) APAP/GTE (APAP followed by GTE), (5) APAP recovery (for one month) and (6) APAP/GTE recovery (for one month). Administration of APAP or GTE resulted in well-documented biochemical and histopathological alterations indicating hepatotoxicity, manifested as augmented concentrations of liver enzymes, hepatocellular necrosis and degeneration, congestion, hemorrhage, inflammation, and fibrosis. The APAP group showed glycogen depletion. Consistent with these changes apoptosis (as detected by caspase-3 immunoreactivity) and oxidative stress (MDA) were greatly increased, whereas antioxidant activities (catalase and GSH) were markedly decreased. These changes were more pronounced in APAP/GTE group, and were not recovered upon cessation of treatments for one month. These results highlight that administration of therapeutic doses of GTE induces hepatotoxicity, and imply that in a situation of clinical paracetamol overdose, administration of GTE is likely to potentiate APAP-induced hepatotoxicity. Further studies are warranted given the increasing use of green tea extract as a dietary supplement.

Keywords: Antioxidants; Apoptosis; Caspase-3 immunohistochemistry; Green tea extract; Hepatotoxicity; Histopathological analysis; Oxidative stress; Paracetamol.