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Effects of Salinomycin and Deferiprone on Lead-Induced Changes in the Mouse Brain
Emilia Petrova1, Yordanka Gluhcheva1, Ekaterina Pavlova1
1Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Str., Bl. 25, 1113 Sofia, Bulgaria.
Abstract:
Lead (Pb) is a highly toxic heavy metal that has deleterious effects on the central nervous system. This study aimed to investigate the effects of salinomycin (Sal) and deferiprone (DFP) on brain morphology and on the content of some essential elements in Pb-exposed mice. Adult male Institute of Cancer Research (ICR) mice were exposed to a daily dose of 80 mg/kg body weight ( b.w.) Pb(II) nitrate for 14 days and subsequently treated with Sal (16 mg/kg b.w.) or DFP (19 mg/kg b.w.) for another 14 days. At the end of the experimental protocol, the brains were processed for histological and inductively coupled plasma mass spectrometry (ICP-MS) analyses. Pb exposure resulted in a 50-fold increase in Pb concentration, compared with controls. Magnesium (Mg) and phosphorus (P) were also significantly increased by 22.22% and 17.92%, respectively. The histological analysis of Pb-exposed mice revealed brain pathological changes with features of neuronal necrosis. Brain Pb level remained significantly elevated in Sal- and DFP-administered groups (37-fold and 50-fold, respectively), compared with untreated controls. Treatment with Sal significantly reduced Mg and P concentrations by 22.56% and 18.38%, respectively, compared with the Pb-exposed group. Administration of Sal and DFP ameliorated brain injury in Pb-exposed mice and improved histological features. The results suggest the potential application of Sal and DFP for treatment of Pb-induced neurotoxicity.
Insights
Salinomycin (Sal) and deferiprone (DFP) show promise in treating lead (Pb) neurotoxicity. These compounds ameliorated brain injury and improved histological features in Pb-exposed mice, suggesting potential therapeutic applications.
Area of Science:
- Toxicology
- Neuroscience
- Pharmacology
Background:
- Lead (Pb) is a neurotoxic heavy metal causing significant central nervous system damage.
- Pb exposure alters essential element concentrations in the brain, including magnesium (Mg) and phosphorus (P).
- Pb-induced neurotoxicity presents pathological changes such as neuronal necrosis.
Purpose of the Study:
- To investigate the neuroprotective effects of salinomycin (Sal) and deferiprone (DFP) in a mouse model of lead (Pb) exposure.
- To evaluate the impact of Sal and DFP on brain morphology and essential element content following Pb intoxication.
- To assess the potential of Sal and DFP as therapeutic agents against Pb-induced neurotoxicity.
Main Methods:
- Adult male ICR mice were exposed to lead (Pb) nitrate (80 mg/kg b.w.) for 14 days.
- Mice were subsequently treated with salinomycin (Sal) (16 mg/kg b.w.) or deferiprone (DFP) (19 mg/kg b.w.) for 14 days.
- Brain tissue was analyzed using histological examination and inductively coupled plasma mass spectrometry (ICP-MS).
Main Results:
- Pb exposure significantly increased brain Pb concentration (50-fold) and elevated Mg and P levels (22.22% and 17.92%, respectively).
- Histological analysis revealed neuronal necrosis in Pb-exposed mice.
- Sal treatment significantly decreased Mg and P concentrations (22.56% and 18.38%) compared to the Pb-exposed group.
- Both Sal and DFP treatments ameliorated brain injury and improved histological features in Pb-exposed mice.
Conclusions:
- Salinomycin (Sal) and deferiprone (DFP) demonstrate significant neuroprotective effects against lead (Pb)-induced toxicity.
- These agents may help restore essential element balance and mitigate pathological brain changes caused by Pb.
- Sal and DFP show potential as therapeutic interventions for lead (Pb) neurotoxicity.
