No abstract

Cadmium (Cd) is an important industrial and environmental pollutant. In animals, the liver is the major target organ of Cd toxicity. In this study, rat hepatocytes were treated with 2.5∼10 μM Cd for various durations. Studies on nuclear morphology, chromatin condensation, and apoptotic cells demonstrate that Cd concentrations ranging within 2.5∼10 μM induced apoptosis. The early-stage marker of apoptosis, i.e., decreased mitochondrial membrane potential, was observed as early as 1.5 h at 5 μM Cd. Significant (P < 0.01) reactive oxygen species (ROS) production at 5 μM Cd and 0.75 h occurred prior to the decrease of the mitochondrial membrane potential, suggesting the involvement of ROS in mitochondrial membrane damage. Glutathione (GSH) level significantly decreased after cell treatment with 5 and 10 μM Cd after 12 h (P < 0.01). Meanwhile, the intracellular free Ca(2+) concentration ([Ca(2+)] i ) of Cd-exposed cells significantly increased (P < 0.01) at 1.5 h, and pretreatment with the calcium chelator Bapta-AM partially blocked Cd-induced apoptosis. This finding indicated that the elevation of [Ca(2+)] i may play an important role in apoptosis. Overall, these results showed that oxidative stress and Ca(2+) signaling were critical mediators of the Cd-induced apoptosis of rat hepatocytes.

Cadmium (Cd) is a well-known hepatotoxic environmental pollutant. We used rat hepatocytes as a model to study oxidative damage induced by Cd, effects on the antioxidant systems, and the role of N-acetylcysteine (NAC) in protecting cells against Cd toxicity. Hepatocytes were incubated for 12 and 24 h with Cd (2.5, 5, 10 µM). Results showed that Cd can induce cytotoxicity: 10 µM resulted in 36.2% mortality after 12 h and 47.8% after 24 h. Lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase activities increased. Additionally, reactive oxygen species (ROS) generation increased in Cd-treated hepatocytes along with malondialdehyde levels. Glutathione concentrations significantly decreased after treatment with Cd for 12 h but increased after 24 h of Cd exposure. In contrast, glutathione peroxidase activity significantly increased after treatment with Cd for 12 h but decreased after 24 h. superoxide dismutase and catalase activities increased at 12 h and 24 h. glutathione S-transferase and glutathione reductase activities decreased, but not significantly. Rat hepatocytes incubated with NAC and Cd simultaneously had significantly increased viability and decreased Cd-induced ROS generation. Our results suggested that Cd induces ROS generation that leads to oxidative stress. Moreover, NAC protects rat hepatocytes from cytotoxicity associated with Cd.

No abstract

Cadmium (Cd)-induced oxidative damage of liver and kidney and the ameliorative impact of baicalein against hepatotoxicity and nephrotoxicity of rats was studied. Male SD rats were handled with either intraperitoneal cadmium (CdCl2, 2mg/kg) and/or oral baicalein (100 mg/kg) for 4 weeks. The results demonstrated that Cd increased the level of GPT, GOT, BUN in serum and the contents of MDA, GSH, decreased the activities of SOD, CAT, GSH-Px in tissues versus control. Conversely, administration of baicalein restored the changes in these parameters to nearly normal levels. The results suggested that the ameliorative impact of baicalein might be because of its antioxidant properties in combating free radical-induced oxidative stress resulting from cadmium chloride.