Low-Dose Hexavalent Chromium Exposure Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Rat Liver

This study investigated the toxic effects of low-dose hexavalent chromium (Cr(VI)) on rat liver. Male specific pathogen-free (SPF) Sprague-Dawley (SD) rats (4-5 weeks of age) were randomly divided into groups: saline, 0.05 mg/kg Cr(VI), and 0.25 mg/kg Cr(VI). The rats were subjected to intratracheal instillation of K₂Cr₂O₇ suspensions or saline once weekly, for a total of five times. The results showed that the accumulation of Cr(VI) in the blood of the 0.25 mg/kg K₂Cr₂O₇ group was significantly higher than that in the saline group. Transmission electron microscopy (TEM) showed that exposure to hexavalent chromium caused endoplasmic reticulum (ER) oedema and a disordered arrangement. The levels of endoplasmic reticulum stress (ERS)-related proteins (ATF6, P-PERK, P-IRE1, Grp78, and CHOP) in the 0.25 mg/kg K₂Cr₂O₇ group were significantly higher than those in the saline group. The expression of apoptosis-inhibitory protein Bcl-2 was significantly lower in the 0.25 mg/kg K₂Cr₂O₇ group than that in the saline group, and the expression of apoptosis protein Bax was significantly higher in the 0.25 mg/kg K₂Cr₂O₇ group than that in the saline group, indicating that Cr(VI) increased apoptosis. These findings revealed that Cr(VI) may be involved in rat liver injury by initiating ERS-mediated apoptosis. The expression of ATF6, P-PERK, P-IRE1, and Bax in the 0.05 mg/kg K₂Cr₂O₇ group was not significantly different from that in the saline group, and the different effects produced by the two different dose groups provide a possible experimental basis for further study of occupational exposure limits.