Oxidative Stress and Ca2+ Signals Involved on Cadmium-Induced Apoptosis in Rat Hepatocyte

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.

Salidroside Protects against Cadmium-Induced Hepatotoxicity in Rats via GJIC and MAPK Pathways

“…Cd is known to induce cytotoxic injury via various cell signal-transduction pathways. Wang et al [40] demonstrated that Cd induced apoptosis via oxidative stress and calcium overload in rat hepatocytes, while Xu et al [41] have demonstrated that Cd resulted in the caspase-dependent apoptosis of neuronal cells, which was induced by [Ca 2+ ] i elevation, implicating ROS and activated MAPK and mTOR pathways. MAPKs are important signaling enzymes that play a critical role in controlling gene expression, cell survival and cell death; however, the regulation of cytotoxic injury by MAPKs is complex [12].…”

Alterations in antioxidant function and cell apoptosis in duck spleen exposed to molybdenum and/or cadmium

“…Typical morphological changes associated with apoptosis were observed in chicken splenic lymphocytes treated with Cd, including membrane bleeds and overall cell shrinkages [17]. Oxidative stress and Ca 2+ signaling pathways have been also suggested as having a significant role in Cd-induced apoptosis [35]. …”

Cerebral ganglion ultrastructure and differential proteins revealed using proteomics in the aplysiid (Notarcus leachii cirrosus Stimpson) under cadmium and lead stress

“…It is reported that Cd 2+ induces the apoptosis in the rat hepatocyte (Wang et al, 2014) and rat cerebral cortical neurons .…”

“…Such oxidative damage is very common during heavy metal treatment (Evlard et al, 2014;Wang et al, 2014). Metal ions can be oxidized or reduced by oxidoreductase in order to repair the damage to the cell and to detoxify.…”