Chromium alters lipopolysaccharide-induced inflammatory responses both in vivo and in vitro.

We demonstrated that pretreatment with chromium (Cr) significantly alters inflammatory responses of mice or macrophage cell lines. The mice were pretreated with 50 and 200 mg L(-1) of Cr dissolved in drinking water for 7 or 21 d, respectively. Then, the mice were challenged with lipopolysaccharide (LPS) or saline for 3 h. The body and liver weights significantly decreased after exposure to 200 mg L(-1) of Cr for both 7 and 21 d. Serious infiltration of inflammatory cells around the artery was found in the liver treated with 200 mg L(-1) of Cr for 7 and 21 d. The levels of tumor necrosis factor-α (TNFα) and interleukin-6 (IL6) in peritoneal macrophage significantly increased after the treatment with 200 mg L(-1) of Cr for 7 d. Moreover, LPS-induced increases in the serum levels and the transcriptional status of some cytokine genes were amplified by the Cr pretreatment. In the in vitro test, the RAW264.7 cell line was pretreated with Cr for 3, 6, 12, and 24 h, followed by stimulation with LPS (1 µg mL(-1)) for 6 h. LPS-induced the increases in TNFα, IL6, Interleukin-1α (IL1α), Interleukin-1ß (IL1ß), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) mRNA levels were significantly promoted by the pretreatment with Cr for 3, 6, and 12 h, whereas they were weakened by the pre-exposure to Cr for 24 h in a concentration-dependent manner. In addition, LPS-induced the release of TNFα and IL6 in the medium was also significantly enhanced or suppressed by the different Cr pretreatment. The results suggested that Cr had the potential to induce immunotoxicity by altering the inflammatory responses.

Oral exposure of mice to cadmium (II), chromium (VI) and their mixture induce oxidative- and endoplasmic reticulum-stress mediated apoptosis in the livers.

Health concerns regarding the environmental heavy metals in wildlife and humans have increased in recent years. We evaluated the effects of exposure of mice to low doses of cadmium (Cd), chromium (Cr) and their mixtures on oxidative- and ER-stress. Male adult mice were orally exposed to Cd (0.5 and 2 mg kg(-1) ), Cr (1 and 4 mg kg(-1) ) and binary Cd+Cr mixtures (0.25 + 05 and 1 + 2 mg kg(-1) ) daily for 36 days. We observed that the bioaccumulation of Cd and Cr in the liver in a dose-dependent manner, and the Cd and Cr contents in the 2 mg kg(-1) Cd and 4 mg kg(-1) Cr treated groups reached 2.43 and 3.46 µg g(-1) liver weight. In addition, treatments with 2 mg kg(-1) Cd, 4 mg kg(-1) Cr or their mixture (1 + 2 mg kg(-1) ) significantly decreased body and liver weights, increased the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and activities of catalase (CAT) and glutathione peroxidase (GPX) in the liver. Moreover, Cd and Cr exposures also elevated the transcription of the oxidative- and endoplasmic reticulum (ER)-stress related genes including Cat, Gpx, heme oxygenase 1 (Ho-1), regulated protein 78 (Grp78), activating transcription factor 6 (Atf6) and proaoptotic CCAAT/-enhancer-binding protein homologous protein (Chop) in a dose dependent manner in the liver. And hepatic cytochrome c levels increased in all Cd, Cr or their mixture treated groups. Furthermore, the transcriptional status and the activities of Caspase 9 and Caspase 3 were increased significantly in the liver when exposed to high doses of Cd, Cr or their mixture. These results suggested that a long period exposure of mice to Cd or Cr has the potential to elicit oxidative- and ER-stress mediated apoptosis in their livers. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 693-705, 2016.

Hepatic oxidative stress and inflammatory responses with cadmium exposure in male mice.

Cadmium (Cd), a non-essential heavy metal, is one of the major environmental contaminants with grave toxicological consequences globally. In the present study, the effects of Cd on hepatic oxidative stress and inflammatory responses in mice were evaluated. Male adult mice were orally exposed to 3, 10 and 30mg/L CdCl2 supplied in the drinking water for 7 and 21 days. Histopathological changes and the alterations of the main parameters related to oxidative stress and inflammatory responses in the liver were observed. Hepatic malondialdehyde (MDA) contents increased significantly after treatment with 30mg/L CdCl2 for 21 days, and the contents of glutathione (GSH) increased significantly in both 10 and 30mg/L CdCl2 treated groups. The hepatic activities of glutathione peroxidase (GPX), catalase (CAT) and glutathione S-transferase (GST) increased significantly after the treatment with 30mg/L CdCl2 for 21 days. In accordance with the enzyme activities, the transcription status of hepatic superoxide dismutase 1 (Sod1), superoxide dismutase 2 (Sod2), Cat, Gpx, Gstα1, glutathione synthetase (Gss), glutathione reductase (Gr) and heme oxygenase 1 (Ho1) were also increased by high dose (30mg/L) or long period (21 days) exposure. In addition, the serum levels of tumor necrosis factor α (TNFα), interleukin 6 (IL6) and interleukin 1ß (IL1ß) increased significantly in the groups treated with 30mg/L CdCl2 for 21 days. And the genes of TNFα, IL6, interleukin 1α (IL1α), inducible nitric oxide synthase (iNOS) and interferon γ (IFNγ) were also increased in the liver of mice when exposed to relative high dose of CdCl2 for 7 or 21 days. Taken together, the results of this study suggested that the exposure to Cd had the potential to induce immunotoxicity accompanied with oxidative stress in the liver of mice.