Changes in antioxidant status in HepG2, 1321N1 and HEK 293 cells in response to cadmium induced-oxidative stress

Lawal, A.O. and Ellis, E.M. (2008) Changes in antioxidant status in HepG2, 1321N1 and HEK 293 cells in response to cadmium induced-oxidative stress. Toxicology, 253 (1-3). pp. 1-2. ISSN 0300-483X (https://doi.org/10.1016/j.tox.2008.07.038)

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Abstract

Cadmium (Cd) has been implicated in a number of pathological diseases and oxidative stress has been proposed as one of its mechanisms of toxicity. In this present study, the toxic effect of 5, 10 and 50 μM of cadmium as cadmium chloride was investigated in three human cell lines: human hepatocellular liver carcinoma cells (HepG2), human astrocytoma cells (1321N1) and human embryonic kidney cells (HEK 293). Antioxidant defence responses of these cells were determined in order to evaluate the extent of oxidative stress induced by this metal after 24hrs exposure. Results indicate that CdCl2 decreases the viability of all three cells in a dose-dependent manner in agreement with earlier reports of Fotakis and Timbrell (2006). However it is clear that HepG2 cells are more sensitive (EC50 = 13.96 μM) than 1321N1 (EC50 = 19.92 μM) and HEK293 (EC50 = 221.8 μM) cells. This may be related to increased uptake, as it has been observed that Cd preferentially accumulates in liver cells in vivo. Increase LDH leakage has earlier been reported to be associated with CdCl2 induced toxicity (Bradley et al., 1987). Table 1 shows a significant increase in LDH leakage in all the three cells at 50 μM. An increase in Reactive Oxygen Species (ROS) was also significant in HepG2 cells but was not significant in 1321N1 and HEK 293 cells .This implies that ROS production may not be involve in CdCl2 induced toxicity in 1321N1 and HEK 293 cells. The results also show that CdCl2 does not deplete GSH in HepG2 cells but does deplete GSH in 1321N1 and HEK 293 cells (Table 1). There was a significant increase in malondialdehyde MDA levels at 50 μM exposure in all the three cells. The results also show a significant increase in the activities of the antioxidant enzymes; GST, GPx, SOD and catalase in the three cell lines at 50 μM CdCl2 with the exception of glutathione reductase in HepG2 cells and catalase in 1321N1 cells. Overall this suggests an adaptive response by the three cells to the CdCl2 insult and this is investigated further by Western blot analysis.