Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats

Autor: Qi Yuan Fan, Xi Min Fan, Ting Wang Xiong, Sheng Song, Jie Liu, Ying Luo, Yu Ming Cao
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Time Factors
Gene Expression
Substantia nigra
Biochemistry
Substantia nigra pars compacta (SNpc)
Rats
Sprague-Dawley
Liver inflammation
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Internal medicine
Dopaminergic neuron loss
medicine
Manganism
Animals
Hepatic transporters
Neuroinflammation
Liver injury
Inflammation
Manganese
Original Paper
Microglia
Behavior
Animal
Pars compacta
Chemistry
Dopaminergic Neurons
Dopaminergic
Neurotoxicity
Brain
General Medicine
medicine.disease
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Liver
Rotarod Performance Test
Neurotoxicity Syndromes
Chronic manganism
Chemical and Drug Induced Liver Injury
030217 neurology & neurosurgery
Injections
Intraperitoneal
Zdroj: Neurochemical Research
ISSN: 1573-6903
Popis: Subacute exposure to manganese (Mn) produced Parkinson’s disease-like syndrome called Manganism. Chronic onset and progression are characteristics of Manganism, therefore, this study aimed to examine Mn toxicity following chronic exposures. Male Sprague-Dawley rats were injected Mn2+ 1 and 5 mg/kg, every 10 days for 150 days (15 injections). Animal body weight and behavioral activities were recorded. At the end of experiments, the brain and liver were collected for morphological and molecular analysis. Chronic Mn exposure did not affect animal body weight gain, but the high dose of Mn treatment caused 20% mortality after 140 days of administration. Motor activity deficits were observed in a dose-dependent manner at 148 days of Mn administration. Immunofluorescence double staining of substantia nigra pars compacta (SNpc) revealed the activation of microglia and loss of dopaminergic neurons. The chronic neuroinflammation mediators TNFα, inflammasome Nlrp3, Fc fragment of IgG receptor IIb, and formyl peptide receptor-1 were increased, implicating chronic Mn-induced neuroinflammation. Chronic Mn exposure also produced liver injury, as evidenced by hepatocyte degeneration with pink, condensed nuclei, indicative of apoptotic lesions. The inflammatory cytokines TNFα, IL-1β, and IL-6 were increased, alone with stress-related genes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1 and metallothionein. Hepatic transporters, such as multidrug resistant proteins (Abcc1, Abcc2, and Abcc3) and solute carrier family proteins (Slc30a1, Slc39a8 and Slc39a14) were increased in attempt to eliminate Mn from the liver. In summary, chronic Mn exposure produced neuroinflammation and dopaminergic neuron loss in the brain, but also produced inflammation to the liver, with upregulation of hepatic transporters. Graphic Abstract Electronic supplementary material The online version of this article (10.1007/s11064-020-03059-2) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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