Sub-chronic cadmium exposure in drinking water dysregulates lipid and glucose metabolisms in ApoE (-/-) mice: molecular insights into the etiology of atherosclerosis

Author(s): Edozie S Okparaa, Yu Wan, Hai-Bin Huang, Jia Song, Wei Zhu, Guangyu Yang,Xiong Lili & Xing-Fen Yang*

Objectives: To provide experimental evidence of heavy metal (Cd)-induced toxicity in compromised hosts (ApoE-/-mice).

Methods: Experiments were performed in male mice, randomly placed into 4 groups according to body weight and administered CdCl2 0, 50, 100 and 200 mg/L, respectively in drinking water consecutively for 4 months. After treatment, changes in body weight were evaluated and mice plasma was analyzed for LDL, HDL, TCHO, TG, insulin and glucose levels. The collected samples were examined histologically in the 4th month. Two-way ANOVA was used for statistical analysis.

Results: The results showed increased plasma LDL and decreased plasma HDL levels across all treatment groups when compared with the blank control and 1st month mice. TCHO and TG levels were also increased across the treatment groups at the same levels of comparisons. Moreover, fasting plasma glucose was elevated and insulin levels were lowered. Histological examination of aortal roots showed a dose-dependent increase in plaque-formation, with plaques being most visible in the group exposed to the highest dose of Cd (200 mg/L). Class 1, with the improving trend, contained 630 (7.01%) of patients; class 2, the stable trend, 7975 (88.52%); and class 3, the worsening trend, 402 (4.47%) of patients. Subjects of class 3 were significantly younger, whereas those of class1 were more frequently women, with a longer duration of diabetes and a worse glycemic control. The multivariate logistic model with the dependent variable worsening trend versus stable trend, showed that age was associated with a reduced probability of worsening trend, duration of diabetes increased the risk of a worsening trend as did women.

Conclusion: Sub-chronic exposure of ApoE-/-mice to Cd causes dysregulation of lipids and glucose metabolisms and ipso facto, atherosclerosis. Translationally, our findings also provide a scientific basis for the justification of the calls for stricter regulations of heavy-metal pollution of public drinking water, especially in compromised populations as modelled by our use of ApoE-/-mice.