Paracetamol is one of the most widely used, studied, and arguably the most notorious hepatotoxic drugs, which is safe at therapeutic doses but causes liver failure when overdosed. When administered at normal doses, paracetamol is metabolized extensively by conjugation with sulphate and glucuronic acid. Exposure to high doses of paracetamol results in increased levels of N-acetyl-p-benzo-quinoneimine (NAPQI), a highly electrophilic metabolite that is considered to be responsible for triggering the ensuing liver damage.

The research, lead by Dr. Sun and his colleagues in Dalian Medical University, has recently been published on April 21,2009 in World Journal of Gastroenterology, investigated the effect of tea polyphenols (TPs) on paracetamol-induced hepatotoxicity. TPs are a large and diverse class of compounds extracted from tea. Recent studies indicate that TPs prevent oxidative stress-related diseases including cancer, cardiovascular diseases, degenerative diseases and other bioactive properties. In recent years there has been a mounting interest in understanding the metabolic benefits of TPs. Liver is the main organ responsible for the metabolism of TPs. And some works have been done in the field of TPs modulated or interacted with drug metabolizing enzymes. However, until now, no one could give a clear explanation about this. Cytochrome P450 (CYP450) enzymes play a pivotal role not only in the metabolism of xenobiotics, and both induction and suppression of several CYP450s may lead to the cellular oxidative stress and tissue injury in response to xenobiotics. Early investigations identified the important roles of CYP2E1, CYP1A2 and intracellular GSH in paracetamol induced hepatotoxicity. But the effect of TPs on paracetamol-induced hepatotoxicity remain unclear. This research gave a clear explanation of TPs' effect on hepatic CYP450 along with CYP2E1 and CYP1A2 expression at both protein and mRNA levels. The results showed that the contents of hepatic CYP450 and CYPb5 were dose-dependently decreased by TPs. Also, TPs reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels dose dependently, indicating that TPs possessed potential hepatoprotective properties and this effect was closely related with their suppression on CYP450 expression. These results provided new information of TPs about their metabolism and the effect of TPs on hepatic drug metabolizing enzyme. This will be important in developing clinically safe and efficient medications related to TPs.

Reference: Chen X, Sun CK, Han GZ, Peng JY, Li Y, Liu YX, Lv YY, Liu KX, Zhou Q, Sun HJ. Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significanly correlated with cytochrome P450 suppression. World J Gastroenterol 2009; 15(15): 1829-1835 wjgnet/1007-9327/15/1829.asp

Correspondence to: Hui-Jun Sun, Professor, Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 west section, Lvshun South Road, Lvshunkou District, Dalian 116044, Liaoning Province,China.

Source:
Lin Tian
World Journal of Gastroenterology