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.

Keywords:

• Copper smelter
• dust
• metals
• rats
• neurobehavioral
• Clara cell protein

Acknowlegements

This study was supported by Grant PB 3459/B/P01/ 2007/33 from Committee for Scientific Research. The skilful works of Dr. Dorota Wiaderna for neurobehavioral studies and Ms. Anna Kubiak and Ms. Edyta Wieczorek MSc., for biochemical analysis is highly appreciated. Many thanks for metals assessment to Prof. Ewa Bulska from ICP-MS Measurement Laboratory, UW.