Cadmium (Cd) is a risk factor for neurodegenerative diseases. The purpose of this study was to compare the effects of meso-2,3-dimercaptosuccinic acid (DMSA) and the polyether ionophorous antibiotics monensin and salinomycin on Cd-induced neurodegenerative alterations in mice. The results show that subacute intoxication of mice with Cd (II) acetate (20 mg/kg body weight (BW) for 14 days) caused a significant accumulation of cadmium (Cd) in the brain. Treatment of Cd-exposed mice with DMSA (20 mg/kg BW for 14 days) significantly increased the Cd concentration in the brains compared to those of the Cd-treated group. However, administration of monensin (20 mg/kg BW for 14 days) or salinomycin (20 mg/kg BW for 14 days) significantly reduced the Cd concentration in the brains of Cd-treated mice compared to the toxic control group. Histopathological analysis of brain tissues from the Cd-treated mice revealed that Cd induced neuronal necrosis, characterized by many shrunken, darkly stained pyknotic neurons with prominent perineuronal spaces. Whereas monensin and salinomycin significantly reduced the adverse effects of Cd on brain morphology of Cd-treated mice, DMSA did not. Monensin slightly increased the copper and iron endogenous levels in the brains of Cd-exposed mice compared to those of the untreated mice. Salinomycin did not affect the concentrations of biometal ions in the brain of Cd-exposed mice compared to untreated controls. The results demonstrated salinomycin to be a better potential chelating agent for treatment of Cd-induced brain injury compared to DMSA and monensin.

Lithium is extensively used in psychiatric practice for the prevention and treatment of manic-depressive disorders. However, neurotoxicity attributed to lithium salts within therapeutic doses was also reported in patients, manifested by transient or persistent neurological deficits. In this study, morphological changes were examined in rats treated acutely and chronically with lithium. Pathological changes were observed in different brain regions including cerebral cortex, cerebellum, medulla oblongata, mesencephalon, thalamus, and pons, using a silver–copper impregnation technique for neurodegeneration. Vacuolization of brain tissue with subsequent formation of spongiosis was the prominent morphological feature following lithium administration. The zones of spongiosis were irregularly distributed throughout the brain. More intensive compact areas with spongiform changes were found in the cerebral cortex and medulla oblongata. Less pronounced vacuolization was noted in the pons and thalamic region. The cerebellum and mesencephalon appeared least affected. Vacuolization in the cerebellar cortex was found at loci with Purkinje cells, but the classical picture of spongiosis was not apparent. Data indicate that both acute and chronic lithium intoxication accelerated neurodegenerative changes normally seen with normal brain aging.