Subacute intratracheal exposure of rats to manganese nanoparticles: Behavioral, electrophysiological, and general toxicological effects

Abstract

The toxicity of manganese-containing airborne particles is an important occupational and environmental problem. In this work, adult male Wistar rats were treated with a nanosuspension of MnO(2) of approximately 23 nm nominal particle diameter, instilled into the trachea for 3, 6, and 9 wk in doses of 2.63 and 5.26 mg Mn/kg. The animals' body weight was checked weekly. At the end of treatment, the rats' spontaneous motility was tested in an open field box. Then, spontaneous and stimulus-evoked cortical activity and action potential of the tail nerve were recorded in urethane anesthesia. The rats were finally dissected, organs weights were measured, and the presence of excess Mn in lung and brain samples was determined using scanning electron microscopy with energy-dispersive x-ray spectroscopy. While control rats had normal weight gain, the body weights of the treated rats ceased to grow from wk 6 on. The relative weight of the lungs increased in the treated rats, and that of the liver decreased, in a dose- and time-dependent manner; Mn was detected in their lung and brain samples. In the open field activity, the percentage of ambulation and rearing decreased while local activity and immobility increased. The latency of the evoked potentials was lengthened, and the conduction velocity of the tail nerve decreased. These results indicate that the Mn content of instilled nanoparticles had access from the airways to the brain, and the resulting damage could be investigated in animals using neuro-functional and general toxicological endpoints.

Effects of subchronic exposure manganese oxide nanoparticles on the central nervous system, lipid peroxidation and antioxidant enzymes in rats

“…Наночастицы оксида марганца ввиду своих небольших размеров и высокой про-никающей способности могут преодолевать гематоэнцефалический барьер и вызывать морфофункциональные нарушения различ-ных отделов центральной нервной системы при различных путях поступления в орга-низм даже в небольших концентрациях [17]. Оценка риска воздействия наночастиц оксида марганца в основном сосредоточена на ингаляции как наиболее вероятном пути поступления в организм.…”

“…Данный процесс сопровожда-ется многократным увеличением АФК [11] и проявляется у экспериментальных жи-вотных нейродегенеративными наруше-ниями уже через 2-3 недели экспозиции [14,19], активацией протеолитического рас-щепления, опосредованного каспазой-3 и про-теинкиназой Сδ (ферментами, участвующи-ми в процессах апоптоза, некроза и воспа-лительных процессах), а также активацией цикла фосфорилирования [5,9,10,13]. По данным других авторов, при интраназаль-ном введении наночастиц оксида марганца (IV) в дозе 2,63 мг/кг массы тела в течение 6 недель у крыс наблюдается появление нейротоксичности по увеличению относи-тельного рефрактерного периода хвостового нерва [17]. При интратрахеальном введении изучаемого соединения в аналогичной дозе в течение 6 недель зафиксировано значи-тельное снижение массы тела, удлинение абсолютного рефрактерного периода хво-стового нерва, уменьшение подвижности животных [17].…”

Effects of subchronic exposure manganese oxide nanoparticles on the central nervous system, lipid peroxidation and antioxidant enzymes in rats

“…This process is accompanied by a multiple increase in the ROS [11] and presents in experimental animals in the form of neurodegenerative disruptions after 2-3 weeks of exposure [8,13], activation of proteolytic cleavage mediated by caspase-3 and protein kinase Sδ (enzymes involved in the processes of apoptosis, necrosis and inflammatory processes), as well as phosphorylation of the activation loop [5,10,12,19]. According to other authors, intranasal introduction of manganese dioxide nanoparticles (IV) to rats at the dose of 2.63 mg/kg of the body mass for 6 weeks results in neurotoxicity to increase the relative refractory period of the caudal nerve [17]. Intratracheal administration of the analyzed compound at a similar dose for 6 weeks leads to a considerable decrease in the body mass, lengthening of the absolute refractory period of the tail nerve, and reduction in the mobility of animals [17].…”

“…According to other authors, intranasal introduction of manganese dioxide nanoparticles (IV) to rats at the dose of 2.63 mg/kg of the body mass for 6 weeks results in neurotoxicity to increase the relative refractory period of the caudal nerve [17]. Intratracheal administration of the analyzed compound at a similar dose for 6 weeks leads to a considerable decrease in the body mass, lengthening of the absolute refractory period of the tail nerve, and reduction in the mobility of animals [17]. Neurotoxicity of manganese dioxide nanoparticles (IV) after intratracheal administration at a dose of 2.63 mg/kg and 5.26 mg/kg is also manifested in the increase the latent period of the cortical potential (total response of large populations of neurons in the cortex to the coming simultaneous flow of impulses arising under the influence of afferent stimulus) in the visual, auditory and somatosensory areas.…”

“…Manganese oxide nanoparticles due to their small size and high penetrating capacities can penetrate though the blood-brain barrier and even small concentrations regardless the route of entry can cause morphofunctional disruptions of various parts of the central nervous system [17]. Assessment of the potential risks of impact of manganese oxide nanoparticles is focused, mainly, on inhalation as the most probable route of entry into the body.…”