Assessment of neurobehavioral and biochemical effects in rats exposed to copper smelter dusts

Abstract

Female Wistar rats were instilled per os by gavage with different copper dust samples: P-25 obtained by passing the test material through a 25 μmsieve, and P-0.1 containing soluble matter and ultra-fine, non-soluble<100 nm particulate matter (PM) fraction. The control group received sterile saline. The effects were studied at day 1, 7, and 30 post-exposure, focusing on bronchoalveolar lavage fluid (BALF) analysis (including biochemistry, cell morphology, cell viability, and Clara cell 16 protein concentration) and pathomorphology of lung. Results of biochemical tests showed a strong pro-inflammatory effect of both particulate fractions. The morphological studies after exposure to P-25 and P-0.1 fractions showed multi-focal infiltrations in the alveoli. Changes in behavioral (radial maze and passive avoidance tests) have shown that memory in groups exposed to dust was impaired. Our findings indicate that both samples of dust from Copper Smelter cause greater and lesser intensity (P-25 > P-0.1) of the symptoms of acute inflammatory reaction immediately 24 h after instillation to rats. Exposure results in dropping CC16 protein level in serum of rats. After one month, previous acute inflammation was resolved and transformed in persistent low-grade inflammation. The low-grade inflammation resulted in induction of neurobehavioral effects probably by changes in "cholinergic anti-inflammatory pathway" in which acetylcholine modulates neurotransmission.

Toxicity of metal oxide nanoparticles in immune cells of the sea urchin

“…Most studies present in the literature have been performed on human cultured cells (Boczkowski and Hoet, 2010). Very little information at the organism's level is available, except for murine models (Halatek et al, 2011). In the latter, authors showed the deep penetration of copper dust inside the organism, which caused inflammation, Reactive Oxygen Species (ROS) elevation and DNA damage.…”

Correlation of serum KL-6 and CC16 levels with neurodevelopmental outcome in premature infants at 12 months corrected age

“…An association between WMI and/or cerebral palsy with maternal, placental, or fetal infections 32 33 34 with high levels of interleukin (IL)-1, IL-6 in amniotic fluid, and IL-6 in cord blood has been demonstrated 35 . Animal studies using inhalation of dust have shown a decrease in CC16 concentration, impaired anti-inflammatory potential, and resulted in early harmful effects not only to the respiratory tract but also to the nervous system 36 37 . Halatek et al 37 .…”

“…Animal studies using inhalation of dust have shown a decrease in CC16 concentration, impaired anti-inflammatory potential, and resulted in early harmful effects not only to the respiratory tract but also to the nervous system 36 37 . Halatek et al 37 . found that the CC16 levels of bronchoalveolar lavage fluid in dust-exposed groups were significantly lower than in the control group.…”

“…Therefore, we speculate that exposure to pulmonary or systemic inflammatory disease resulted in lower CC16 and higher KL-6 protein levels which lead to persistent low-grade inflammation, which consequently resulted in induction of neurobehavioral effects. This may be due to changes in cholinergic anti-inflammatory pathways modulated by acetylcholine neurotransmission 37 . In addition, BPD is a recognized antecedent of cerebral palsy and adverse motor outcomes 39 40 41 42 .…”

Chronic copper exposure elicit neurotoxic responses in rat brain: Assessment of 8-hydroxy-2-deoxyguanosine activity, oxidative stress and neurobehavioral parameters

“…After uptake it gets distributed within the different cells, detoxification and elimination in the body is maintained by the elegant system which make sure a regular and adequate supply of the micronutrient whereas concurrently avoiding excess levels (4). Copper is a prominent ecotoxicant and human being gets exposed to copper via consumption of water, food and also by inhalation of industrial dust (5)(6). Recent reports suggest that agriculture workers handling of Cu-derived agrochemicals and also Cu-IUDs used by women lead to high plasma levels of copper (7).…”