Neurological effects of subchronic exposure to dioctyl phthalate (DOP), lead, and arsenic, individual and mixtures, in immature mice

Weiwei Feng; Xueshan Wu; Guanghua Mao; Ting Zhao; Wei Wang; Yao Chen; Min Zhang; Liuqing Yang; Xiangyang Wu

doi:10.1007/s11356-019-06823-2

Neurological effects of subchronic exposure to dioctyl phthalate (DOP), lead, and arsenic, individual and mixtures, in immature mice

Environ Sci Pollut Res Int. 2020 Mar;27(9):9247-9260. doi: 10.1007/s11356-019-06823-2. Epub 2020 Jan 8.

Authors

Weiwei Feng^{1

2}, Xueshan Wu³, Guanghua Mao¹, Ting Zhao³, Wei Wang⁴, Yao Chen^{1

2}, Min Zhang³, Liuqing Yang⁵, Xiangyang Wu^{6

7}

Affiliations

¹ School of the Environment and Safety Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China.
² Institute of Environmental Health and Ecological Security, Jiangsu University, Zhenjiang, Jiangsu, China.
³ School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China.
⁴ School of Food and Biological Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China.
⁵ School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China. yangliuqing@ujs.edu.cn.
⁶ School of the Environment and Safety Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China. wuxy@ujs.edu.cn.
⁷ Institute of Environmental Health and Ecological Security, Jiangsu University, Zhenjiang, Jiangsu, China. wuxy@ujs.edu.cn.

PMID: 31916164
DOI: 10.1007/s11356-019-06823-2

Abstract

Dioctyl phthalate (DOP) (200, 500, and 1000 mg kg^-1 bw, i.g.), Pb (Ac)₂ (50 mg L^-1, p.o.), and NaAsO₂ (10 mg L^-1, p.o.) were administered individually and as mixtures to weanling male mice for 8 weeks. It was observed that Pb, As, and DOP exposure could significantly inhibit the growth and development of mice. Compared with the Pb, As, and Pb + As groups, the activities of iNOS and TNOS were significantly increased, the levels of AChE and SOD were significantly decreased, and the level of MDA was significantly increased in the Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups. The factorial analysis shows that the iNOS, TNOS, and AChE present synergistic effects on Pb, As, and DOP. A significant increase of escape latency and a significant decrease of original platform quadrant stops were observed between Pb + As + DOP-H and Pb + As groups. The factorial analysis shows that there was a synergistic effect on Pb, As, and DOP. Compared with that of the control group, the expression levels of caspase-3 and Bax expression in Pb + As, DOP-H, Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups were significantly increased in the hippocampus. The expression levels of Bcl-2 expression decreased significantly and the Bax/Bcl-2 ratio increased significantly. Pathological alterations on the hippocampus were found in exposed groups. This result shows that combined exposure of Pb, As, and DOP could induce neurotoxicity, of which possible mechanism is hippocampal neuronal apoptosis. Graphical abstract This study shows that there were three components with eigenvalues greater than 1, which together explained 89.40% of total variance. The first component (PC1) showed high loadings on B-SOD, L-SOD, B-MDA, L-MDA, K-MDA, iNOS, tNOS, and AChE and accounted for 46.55% of the total variance after Varimax rotation. PC2 accounted for 23.81% of the total variance with high loadings on B-As, L-As, K-As, and K-SOD, whereas PC3 showed high loadings on B-Pb, L-Pb, and K-Pb and accounted for 19.04% of the total variance.

Keywords: Dioctyl phthalate (DOP); Heavy metals; Mixture exposure; Neurotoxicity.

MeSH terms

Animals
Apoptosis / drug effects*
Arsenic* / metabolism
Arsenic* / toxicity
Diethylhexyl Phthalate* / metabolism
Diethylhexyl Phthalate* / toxicity
Hippocampus / physiopathology*
Lead / metabolism
Lead / toxicity*
Male
Mice

Substances

Lead
Diethylhexyl Phthalate
Arsenic

Abstract

MeSH terms

Substances

Grants and funding