Neurobehavioural and Neurochemical Changes in Arsenic Induced Cerebellar Toxicity in Male Sprague-Dawley Rats: An Experimental Study

Abstract

Introduction: Sodium arsenite, an inorganic arsenic, is naturally present at high level (>50 μg/L) in ground water. Drinking ground water is the biggest threat to public health. Though, there are numerous reports on arsenic neurotoxicity, the arsenic effect on cerebellar neurotoxicity remains vague especially its chronic effect on its neurobehavioural and neurochemical alterations. Aim: To evaluate the neurobehavioural and neurochemical alterations caused by sodium arsenite in cerebellum of rats. Materials and Methods: This experimental study was conducted in the Central Animal House at Sri Devaraj Urs Academy of Higher Education and Research (SDUAHER) from November 2019 to February 2020 for a period of 90 days. Total 16 male spraguedawley rats were randomised into two equal groups. Group I: Control, received normal saline. Group II: Sodium arsenite, Doses of 50 Parts per Millions (PPM) for 90 days through oral gavage. Rats were subjected to Open Field Test (OFT) for locomotor and exploratory behaviour and Beam Walking Test (BWT) for motor coordination and balance. Following behavioural tests, rats were anaesthetised. Blood was drawn from a retro-orbital puncture. Brains were dissected and cerebellum was separated. Concentration of Malondialdehyde (MDA), Nitric Oxide (NO) and activity of Glutathione Peroxidase (GPx) were assessed spectrophotometrically in serum and cerebellum of rats. Mean±SD was used for normally distributed data and groups were compared using independent t-test, whereas for non normally distributed data, Median (25th-75th Percentile) was used and Mann-Whitney U-test was used to compare between two groups. Results: Arsenic-treated rats showed a significant increase in arsenic concentration in serum and cerebellum (5.5±1.6 ng/mL, 2.76±0.56 µg/g, respectively) compared to control (1.14±0.43 ng/mL, 0.65±0.29 µg/g, respectively). There was a significant decrease in locomotor and exploratory behaviour and impairment in motor coordination and balance in arsenic treated rats with a p-value <0.001 in comparison with control rats. The arsenic treated rats had significantly enhanced concentration of MDA and NO level and reduced activity of GPx in serum {16.84 (13.84-18.87), 33.79 (30.05-37.17) nmol/mL, and 6.89 (5.24- 8.5) mmoles of Reduced glutathione (GSH) oxidised/min/mL, respectively} compared to control {8.81 (8.36-9.48), 17.66 (15.33-21.29) nmol/mL, and 15.16 (12.77-16.59) mmoles of GSH oxidised/min/mL, respectively} and also found increased concentration of MDA and NO level and reduced activity of GPx in tissue {7.98 (7.14-8.92), 24.67 (21.4-28-22) nmol/mg of protein and 2.66 (1.19-3.86) mmoles of GSH oxidised/min/ mg protein, respectively} compared to control {3.02 (2.35-3.61), 13.93 (11.0-16.16) nmol/mg of protein and 7.63 (7.08-9.19) mmoles of GSH oxidised/min/mg protein, respectively}. Conclusion: The oral administration of sodium arsenite at the doses of 50 PPM for 90 days showed interesting alterations in neurobehavioural and neurochemical parameters related to cerebellum of rats.