Effects Of Environmental Heavy Metals Cadmium And Chromium On The Anti-oxidative And Immune System

Heavy metal is a metal that density is greater than 4.5g/cm³,such as copper?Cu?,gold?Au?,silver?Ag?,lead?Pb?,cadmium?Cd?,chromium?Cr?,mercury?Hg?,etc.It is used widely in all industry,such as electroplating,leather,textile.At present,it is pay more attention to the problem that the widely application of the heavy metals lead to environmental pollution and adverse impacts on the ecosystems.This study,in Cd and Cr as an example,explores the influence of heavy metals to oxidative and immune system,in order to provide certain theoretical basis of Heavy metal poisoning and prevention.Cadmium?Cd?,a non-essential heavy metal,is one of the major environmental contaminants with grave toxicological consequences globally.The effects of low dose of Cd on oxidative stress and inflammatory responses in the liver of mice were evaluated.Male adult mice were orally exposed to 3,10 and 30 mg/L CdCl₂ supplied in the drinking water for 7 and 21 days.Histopathological changes and the alterations of the main parameters of oxdative stress and inflammatory responses in the liver were observed.Hepatic malondialdehyde?MDA?contents increased significantly after treatment with 30 mg/L CdCl₂ for21 days,and the contents of glutathione?GSH?increased significantly in both 10 and 30 mg/L CdCl₂ treated groups.In addition,the hepatic activities of glutathione peroxidase?GPX?,catalase?CAT?and glutathione S-transferase?GST?increased significantly after treatment with 30 mg/L CdCl₂ for 21 days.In accordance with the enzyme activities,the transcription status of hepatic Sod1,Sod2,Cat,Gpx,Gsta1,Gss,Gr and Ho1 were also increased by high dose?30 mg/L?or long period?21 days?exposure.In addition,the serum levels of TNF?,IL6and IL1?increased significantly in the groups treated with 30 mg/L CdCl₂ for 21 days.And the main genes of TNF?,IL6,IL1?,iNOS and IFN?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 exposure to low levels of Cd had the potential to induce immunotoxicity accompanied with oxidative stress in the liver of male mice.Oxidative stress and inflammatory responses induced by Cd were evaluated in a RAW264.7 cells.A significant decrease in the viability of cells was observed in the group treated with 3?M Cd for 24hours.The mRNA levels of TNF?,IL6,IL1?and IL1?increased by low dose?0.3 and 1?M?and short time?6 hours?exposure and decreased by high dose?3?M?or long time?24 hours?exposure in response to Cd.Moreover,the pretreatment with Cd for 24 hours would inhibit the transcriptional status of TNF?,IL6,IL1?and IL1?in RAW264.7 cells and the release of these cytokines in the medium in a dose-dependent manner in response to LPS treatment for 6 hours.On the other hand,the Cd exposure elicited oxidative stress not only by disturbing the transcriptional status of genes including Sod,Cat,Gpx,Gst1a,Nqo1,Ho-1 but also the enzyme activities of SOD,CAT and GST in RAW264.7cells.The effects of Cd on the mRNA levels and activities of anti-oxidative were depended on the exposure period and dose in RAW264.7 cells.These results suggested that Cd exposure generated oxidative stress and decreased the inflammatory responses in a murine macrophage cells.And the oxidative stress may be a possible mechanism to explain the heavy metals caused the dysregulation of immune function in in vitro system.Chromium?Cr?,one of the most common heavy metals in the ecosystem,is considered as the environmental contaminants which constituted serious risks for human and wildlife.The inflammatory responses induced by Cr were evaluated both in mice and in RAW264.7cell line.Male adult mice were exposed to 0,50 and 200 mg/L Cr supplied in the drinking water for 7 and 21 days,then treated with/without LPS?200?g/mice?for 3 h.The body and liver weights decreased significantly after exposure to 200 mg/L Cr for both 7 and 21days.The serious infiltration of inflammatory cells around the artery was found in the liver especially treated with 200 mg/L Cr for 7 and 21 days.The levels of TNF?and IL6 in peritoneal macrophage increased significantly after the treatment with 200 mg/L Cr for 7 days.Furthermore,when the mice were pretreated with Cr,the transcriptional status of some cytokines increased both in the liver and spleen in response to 200?g/mouse LPS stimulus for 3 h.In addition,the levels of TNF?and IL6 in the Cr pretreated groups were also high than those in the control group.In the in vitro test,the RAW264.7 cell line was pretreated with various concentrations of Cr for 3,6,12 and 24 h then stimulated with LPS?1?g/mL?for 6 hours.We observed that the mRNA levels of TNF?,IL6,IL1?,IL1?,iNOS and Cox2 increased extremely in response to LPS treatment,and the levels significantly promoted by treatment Cr for 3 and 6 h,or 0.5 and 2 mM Cr for 12 h.And then,they decreased in a concentration dependent manner when exposed to Cr for24 h.And the releases of TNF?and IL6 in the medium increased significantly in 8 and 0.5?M Cr treated groups in comparison with the LPS treated group,respectively.Their levels in the medium tended to decrease in all Cr treated groups when the exposure time extended to 24 h.Taken together,the results of this study suggested that exposure to Cd had the potential to induce immunotoxicity by means of altering the inflammatory responses in the mice both in vivo and in vitro.