Abstract
The brain is one of the critical organs particularly susceptible to the damaging effects of chronic arsenic poisoning and there is a growing body of evidence that suggest that oxidative stress plays a key role in the pathogenesis of neurodegenerative disorders. The aim of this present work was to comparatively assess biomarkers of oxidative stress and status of antioxidant enzyme activities in the brains of muskrats and squirrels breeding in arsenic endemic areas, specifically near the vicinity of the abandoned Giant mine site (~2 km radius), and an intermediate location approximately 20 km from the mine area and in reference locations spanning 52-105 km from the city of Yellowknife, Northwest Territories (Canada). Analysis included measurement of total arsenic and cadmium concentration in the nails, brain, and stomach content of muskrats and squirrels, in addition to biochemical evaluation of lipid peroxidation levels and antioxidant enzymes defense: catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the brain tissues. The results revealed that arsenic concentration in the nails of muskrats collected closest to the vicinity of the mine area was in the range of 11 to 35.1 times higher than those from the reference site. The maximum concentration of arsenic in the nails of muskrats from the intermediate location was 47.6 times higher than the maximum concentration observed in the reference muskrats. Cadmium was generally undetected in the nails of muskrats and squirrels from the three sampling locations. Arsenic in the gut contents of muskrats from the arsenic affected area was 4.5 to 49.1 times higher than those from the reference site. Cadmium levels in the guts of muskrats from the mine area almost doubled those from the reference site. Arsenic accumulated in the nails of squirrels from the areas closest to the mine but was undetected in the squirrel nails from the reference location. The maximum arsenic levels in the stomach content of squirrels from the mine area was ~40 times higher than those from the reference site. Arsenic did not accumulate in the brains of muskrats, but cadmium was detected in a few brains of muskrats. Brains of squirrels from the mine area and intermediate locations accumulated both arsenic and cadmium. The brains of squirrels and muskrats from the arsenic affected area showed no evidence of increased lipid peroxidation compared to the animals from the reference site. However, SOD, CAT and GPx activities in the brains of animals from the arsenic endemic areas tended to be higher compared to the control sites. This is the first study documenting evidence of oxidative stress and altered antioxidant enzyme activities in brains of wild rodent population in arsenic endemic areas of Canada.