Green Tea Extract-induced Acute Hepatotoxicity in Rats

Abstract

Although green tea is considered to be a healthy beverage, hepatotoxicity associated with the consumption of green tea extract has been reported. In the present study, we characterized the hepatotoxicity of green tea extract in rats and explored the responsible mechanism. Six-week-old IGS rats received a single intraperitoneal (ip) injection of 200 mg/kg green tea extract (THEA-FLAN 90S). At 8, 24, 48 and 72 hrs and 1 and 3 months after exposure, liver damage was assessed by using blood-chemistry, histopathology, and immunohistochemistry to detect cell death (TUNEL and caspase-3) and proliferative activity (PCNA). Analyses of malondialdehyde (MDA) in serum and the liver and of MDA and thymidine glycol (TG) by immunohistochemistry, as oxidative stress markers, were performed. Placental glutathione S-transferase (GST-P), which is a marker of hepatocarcinogenesis, was also immunohistochemically stained. To examine toxicity at older ages, 200 mg/kg green tea extract was administered to 18-wk-old female rats. In 6-wk-old rats, 12% of males and 50% of females died within 72 hrs. In 18-wk-old rats, 88% died within 72 hrs. The serum levels of aspartate aminotransferase, alanine aminotransferase and/or total bilirubin increased in both males and females. Single-cell necrosis with positive signs of TUNEL and caspase-3 was seen in perilobular hepatocytes from 8 hrs onward in all lobular areas. PCNA-positive hepatocytes increased at 48 hrs. MDA levels in the serum and liver tended to increase, and MDA- and TG-positive hepatocytes were seen immunohistochemically. GST-P–positive hepatocellular altered foci were detected in one female rat at the 3-month time point. In conclusion, a single injection of green tea extract induced acute and severe hepatotoxicity, which might be associated with lipid peroxidation and DNA oxidative stress in hepatocytes.

Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury

“…According to clinical observational research results, individuals who fasted or lost significant weight seemed to be more prone to liver injury, or liver injury was more severe when consuming GTE (Pillukat et al, 2014;Zheng et al, 2016). Although the hepatotoxicity of GTE and its main component EGCG has been reported (Emoto et al, 2014;Wang et al, 2015), it is not clear why there are more reports of liver injury when GTE is used for weight loss.…”

Safety Evaluation of Green Tea Polyphenols Consumption in Middle‐aged Ovariectomized Rat Model

“…Previous experimental studies suggest that administration of high dose of green tea extract may result in hepatotoxicity (Emoto and others ; Mazzanti and others ). For example, administration of high‐dose green tea extracts to non‐fasted dogs induced liver, gastrointestinal, and renal toxicities (Kapetanovic and others ; Wu and others ).…”

Epigallocatechin Gallate for Management of Heavy Metal-Induced Oxidative Stress: Mechanisms of Action, Efficacy, and Concerns

“…route, there is one study in which the EGCG dose (80 mg/kg/d for 49 days) protecting against Pb-induced damage to rat testes [ 108 ] was not far from an EGCG dose (108 mg/kg, a single i.p. treatment), that was found to induce toxic effects in the liver of rats [ 156 ]. However, some EGCG doses protecting against HM toxicity administered through the oral or intraperitoneal route in mice and rats were much lower than doses reported to cause toxic effects in rodent models.…”