Abstract
This work was designed to study MCT effect in histopathological analysis of hippocampus (HC) and parahippocampal cortex (PHC) and in oxidative stress (OS) parameters in brain areas such as hippocampus (HC), prefrontal cortex (PFC), and striatum (ST). Swiss mice (25–30 g) were administered a single i.p. dose of MCT (5, 50, or 100 mg/kg) or 4% Tween 80 in saline (control group). After 30 minutes, the animals were sacrificed by decapitation and the brain areas (HC, PHC, PFC, or ST) were removed for histopathological analysis or dissected and homogenized for measurement of OS parameters (lipid peroxidation, nitrite, and catalase) by spectrophotometry. Histological evaluation of brain structures of rats treated with MCT (50 and 100 mg/kg) revealed lesions in the hippocampus and parahippocampal cortex compared to control. Lipid peroxidation was evident in all brain areas after administration of MCT. Nitrite/nitrate content decreased in all doses administered in HC, PFC, and ST. Catalase activity was increased in the MCT group only in HC. In conclusion, monocrotaline caused cell lesions in the hippocampus and parahippocampal cortex regions and produced oxidative stress in the HC, PFC, and ST in mice. These findings may contribute to the neurological effects associated with this compound.
Highlights
Monocrotaline (MCT) is a pyrrolizidine alkaloid produced by Crotalaria genus, which causes hepatotoxic effects in animals and man [1, 2]
Histological evaluation of brain structures of the rat treated with MCT (50 or 100 mg/kg) revealed lesions in the hippocampus and parahippocampal cortex compared to control (score: 0 (0-1))
Immunohistochemistry analysis in our results showed an increase of caspase 3, indicating apoptosis caused by MCT in relation to control animals (Figure 2)
Summary
Monocrotaline (MCT) is a pyrrolizidine alkaloid produced by Crotalaria genus, which causes hepatotoxic effects in animals and man [1, 2]. Pyrrolizidine alkaloids are activated in vivo by liver cytochrome P450 mixed-function oxidases, producing generation of electrophilic pyrrolic intermediates [3]. Dehydromonocrotaline inhibits the activity of the respiratory chain complex I. Preliminary studies show that MCT causes lesions in some organs, such as liver [11] and lungs [12]. There are reports of histological changes in these organs and MCT neurotoxicity is associated with its lipophilicity [9, 13], but there is a little information about the associated histological changes in the central nervous system (CNS)
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