Adverse neurological effects after exposure to copper, manganese, and mercury mixtures in a Spraque-Dawley rat model: an ultrastructural investigation

ABSTRACT

Exposure to environmental metal pollutants is linked to oxidative stress and the subsequent development of neurological disease. In this study, the effects of copper, manganese, and mercury, were evaluated at X100 the World Health Organization safety limits for drinking water. Using a Sprague-Dawley rat model, following exposure for 28 days, the effects of these metals on biochemical blood parameters and tissue and cellular structure of the brain were determined. Biochemical analysis revealed no hepatocellular injury with minor changes associated with the hepatobiliary system. Minimal changes were found for renal function and the Na⁺/K⁺ ratio was reduced in the copper and manganese (Cu + Mn) and copper, manganese, and mercury (Cu, Mn + Hg) groups that could affect neurological function. Light microscopy of the brain revealed abnormal histopathology of Purkinje cells in the cerebellum and pyramidal cells in the cerebrum as well as tissue damage and fibrosis of the surface blood vessels. Transmission electron microscopy of the cerebral neurons showed microscopic signs of axonal damage, chromatin condensation, the presence of indistinct nucleoli and mitochondrial damage. Together these cellular features suggest the presence and influence of oxidative stress. Exposure to these metals at X100 the safety limits, as part of mixtures, induces changes to neurological tissue that could adversely influence neurological functioning in the central nervous system.

KEYWORDS:

• Brain
• cerebellum
• copper
• cortex
• manganese
• mercury
• mixtures
• nervous tissue
• oxidative stress

Acknowledgments

The authors would like to thank the National Research Foundation for funding and the staff at the UPBRC for their involvement with the implementation and termination of the animal study and the staff of the Laboratory for Microscopy and Microanalysis of the University of Pretoria, for the use of their microscopes and facilities.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Additional information

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Research Foundation under grant number [92768].