Inhibitory Effect Of Tea Catechins On Pb～(++)-induced Oxidative Injury In Cell Models And Its Mechanism

Recent studies have shown that lead causes oxidative stress by inducing the generation of reactive oxygen species (ROS) and reducing the antioxidant defense system of cells, which suggests that antioxidants may play an important role in the treatment of lead poisoning. As a kind of excellent scavenger of free radicals, modulator of immune systems and chelator of heavy metal, whether tea catechins have the protective effects on altered oxidative stress parameter after lead treatment in in vitro and in vivo systems remains unclear. The present study was designed to elucidate whether tea catechins have any protective effects on lipid peroxidation damage, cell membrane fluidity , intracellular ROS, free intracellular calcium and glutathione level in lead -exposed cell models. Results showed:1. Protective effect of tea catechins on lipid peroxidation in HepG2 cells exposed to leadLiver has been considered as the target organs for the toxic effects of lead. Chronic exposure to this biotoxicant leads to hepatitis, cirrhosis and possibly causes cell proliferation and mutations. And so it is important to study the mechanism of liver toxicity of Lead and protective effect of antioxidants.Effect of tea catechins on lipid peroxidation in HepG2 cells exposed to lead was studied by MTT method and ESR spin trapping technique in this paper. Results showed that tea catechins significantly increased cell viability, decreased lipid peroxidation levels and protected cell membrane fluidity in lead- exposed hepG2 cells in a dose-dependent manner. And cotreatment with EGCG and EC, ECG and EGCG showed synergistically protective effect. The results suggest that tea catechins supplementation may have a role to play in modulating oxidative stress in lead -exposed HepG2 cells.2. Lead induced intracellular ROS accumulation and free calcium increase in PC12 cells and antagonistic action of tea catechins.A growing amount of evidence indicates that cellular damage mediated by ROS may be involved in the pathology associated with lead intoxication. Lead characteristically perturbs processes linked to calcium and the calcium messenger system, which are due to similarities between Ca2+ and Pb2+. In the present study, PC 12 cells, which exhibit numerous characteristics similar to sympathetic neurons, were used as a neuronal model to examine the mechanism of Pb2*-induced cytotoxicity and antagonistic action of tea catechins. Results showed that tea catechins protected PC 12 cells against the lead -induced decrease in cellular viability and increase in ROS accumulation in a dose -dependent mode, and the galloylated catechins showed stronger effect than that of non-galloylated catechins. In the presence of tea catechins, the increased free intracellular calcium and the decrease of the mitochondrial membrane potential induced by Pfr" were also clearly suppressed. The results indicated that tea catechins was able to prevent the alterations insome oxidative stress parameters in lead-exposed cell models.3. Elevation of glutathione levels by Pb"1"1" in PC12 cells and effect of tea catechins.GSH is proposed to protect the cell against metal toxicity through a chelation mechanism, removal of generated reactive oxygen species and maintenance of the redox state of other thiols. In the present study, it was found that lower concentration of Pb^ significantly increased intracellular free GSH and GSSG level and protein sulphyryl groups(PSH) and glutathione -protein mixed disulphide(GSSP) levels. And Pb^ significantly decreased GSH/GSSG ratio and glutathione resuctase activities in a dose -dependent manner, which will render cells more susceptible to oxidative damage. 100 u M EC and ECG supplementation resulted in an increased GSH/GSSG ratio and glutathione resuctase activities. To be surprised, 100 u M EGC showed reverse action, which is related to the higher cell toxicity of EGC. The results suggested that the beneficial role for tea catechins on glutathione levels in lead-exposed PC 12 cells was related to its ability t...