Effects of subacute cadmium exposure and subsequent deferiprone treatment on cadmium accumulation and on the homeostasis of essential elements in the mouse brain.

ABSTRACT

INTRODUCTION: Cadmium (Cd) is а hazardous multi-organ toxin. In this study, we provide the first results about the effect of oral administration of deferiprone (DFP) on Cd accumulation and on the homeostasis of essential elements in the brain of Cd-exposed mice. METHODS: Adult Institute of Cancer Research (ICR) male mice were randomized into four experimental groups untreated controls - administered distilled water for 28 days; Cd-exposed group - exposed to 18 mg/kg body weight (b.w.) Cd(II) acetate for 14 days followed by the administration of distilled water for two weeks; Cd + DFP (low dose) - Cd-intoxicated mice subsequently treated with 19 mg/kg b.w. DFP for two weeks; and Cd + DFP (high dose) - Cd-exposed mice administered high-dose DFP (135 mg/kg b.w.) for 14 days. Brains were subjected to inductively coupled plasma-mass spectrometry (ICP-MS) and histological analysis. RESULTS: The results revealed that exposure of mice to Cd for 14 days significantly increased Cd concentration and significantly decreased magnesium (Mg), phosphorus (P), and zinc (Zn) contents in the brain compared to untreated controls. This effect was accompanied by necrotic-degenerative changes in both the cerebrum and cerebellum. Oral administration of low-dose DFP to Cd-exposed mice decreased the concentration of the toxic metal in the brain by 16.37% and restored the concentration of the essential elements to normal control values. Histological analysis revealed substantially improved cerebral and cerebellar histoarchitectures. In contrast, oral administration of high-dose DFP increased Cd content and significantly decreased selenium (Se) concentration in the brain. Necrotic neurons and Purkinje cells were still observed in the cerebral and cerebellar cortices. CONCLUSION: The results demonstrated that oral administration of DFP at low doses has a better therapeutic potential for the treatment of Cd-induced brain damage compared to high doses.