Objective To examine the effects on liver and kidney functions,DNA methylation,and the expression of demethylation enzyme 1(Tet1) in mice after sub acute exposure (4 weeks) to cadmium chloride.
Methods Forty-eight SPF grade KM mice were randomly grouped into four groups:control (ddH2O),CdCl2 17.5 mg/kg,25 mg/kg,and 35 mg/kg groups.The mice were treated with cadmium chloride by gavage,once a day,five days a week,for four weeks.Then they were neutralized after CO2 anesthesia.Items to be measured included liver and kidney organ coefficients,blood routine and biochemical indicators,pathological examinations of liver and kidney tissue samples,whole genome DNA methylation levels,as well as Tet1 mRNA and protein expressions.
Results The activity and mental state of mice were lower in the 35 mg/kg group.Significant differences in mice weights among all exposure durations and CdCl2 exposure doses were observed,and the interaction between exposure duration and dosage was confirmed (P < 0.05).Compared with the control group,the liver weights and coefficients of the male mice in the 25 mg/kg and 35 mg/kg groups had significant differences (P < 0.05).In female and male mice,the blood routine indicators such as white blood cell (WBC),blood platelet (PLT),and lymphocyte (LYM) had significant differences among all cadmium chloride exposed groups (P < 0.05);in the male mice,WBC,PLT,LYM,and RBC had differences among all cadmium chloride exposed groups (P < 0.05).Besides,as for the blood biochemical indicators,alanine aminotransferase (ALT) and alkaline phosphatase (ALP) of liver functions as well as uric acid (UA),blood urea nitrogen (BUN),and creatinine (CR) of kidney functions showed significant differences between two mouse genders (P < 0.05).The results of histopathologic analysis showed that liver and kidney pathological changes of male mice were found in the 25 mg/kg and the 35 mg/kg groups.The Tet1 protein and mRNA expression levels only in the male liver and kidney samples were obviously different among various dose groups (P < 0.05).The results of pyrosequencing showed that the male mice had significant differences in methylation in kidney and liver among various dose groups (P < 0.05),which were negatively correlated with Tel1 mRNA expression (r=-0.473,P < 0.05;r=-0.134,P < 0.05).
Conclusion Subacute cadmium exposure could induce kidney and renal injury in mice,and show gender differences in expressions of whole genome methylation and demethylation enzyme Tet1.Tet1 could regulate the global methylation in liver and kidney of male mice.
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