Arsenic and vanadium co-exposure induced cerebellar neurotoxicity: aggravates apoptosis, inflammation, oxidative stress, and locomotor deficits in juvenile BALB/c mice

Abstract

In this research, we studied the individual and combined effects of arsenic and vanadium on the cerebellum of mice. Mice were subjected to arsenic and vanadium individually and in combination for 21 days. Twenty-four hours after the last administration, the mice were subjected to open field and rotarod tests after which the cerebellar tissues were harvested for biochemical analysis of the levels of malondialdehyde (MDA), catalase (CAT), caspase-3, tumor necrosis factor alpha (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), interleukin-1 beta (IL-1β), dopamine, serotonin, acetylcholine, and acetylcholinesterase. The hematoxylin and eosin stain was employed to explore histopathological event in the cerebellar tissue. The mice were either subjected to arsenic or vanadium or their combination showed significant short fall respectively in the open field and rotarod tests. There was an aggravated shortfall in the mice exposed to arsenic+vanadium combination. Furthermore, our data showed that exposure to the combination of arsenic and vanadium provoked synergistic neurotoxicity in the cerebellum of the mice subjected to arsenic+vanadium resulting into disturbance of locomotor and the production of neurodegenerative characteristics in the cerebellum. Relative to the control group, the levels of MDA, CAT, caspase-3, TNF-α, Nrf2, IL-1β, dopamine, serotonin, acetylcholine, and acetylcholinesterase were adversely modulated in the arsenic-treated, vanadium-treated and in the group exposed to the combination of arsenic+vanadium. The histopathology of the cerebellum showed that exposure to arsenic, vanadium, and their combination produced neurodegenerative effects. The study conclude that exposure to arsenic and vanadium, as well as their combination, had a considerable influence on cerebellar tissue, culminating in a synergistic toxic effect.