OBJECTIVES: Arsenic (As) is ubiquitously distributed in the environment and is known as a human carcinogen. In this study, acute As toxicity at lethal dosage in rats and mice was evaluated, and As-induced hepatotoxicity was characterized. METHODS: Male Sprague-Dawley rats, male ICR mice and trivalent inorganic As, sodium arsenite, were used in this experiment. LD50 and LD100 were calculated from 24-hour lethality after the single subcutaneous administration of As into rats and mice. Serum and liver were collected from the surviving animals. The activities of ALT, AST and gamma-GT in serum were determined, and the concentrations of MDA, GSH and CYP450 in liver were analyzed. RESULTS: The LD50 and LD100 of sodium arsenite were calculated as 12 mg/kg and 13 mg/kg for rats, and 16.5 mg/kg and 19 mg/kg for mice, respectively. Thus, the rat was more susceptible than the mouse to the acute lethal toxicity of As. The histopathological changes induced by As were similar between rats and mice. AST was increased in high-dose As-treated rats and mice, whereas ALT was increased in high-dose As-treated mice but not in rats. gamma-GT was not significantly changed between the two animal groups. As increased lipid peroxidation, but decreased GSH and CYP450 in the liver of both rats and mice, in dose-dependent patterns. These results indicate that oxidative stress might be one of the mechanisms in As-induced hepatotoxicity. CONCLUSION: Rats were more susceptive than mice to acute As toxicity, and oxidative stress might play a part in liver injury induced by As.
Animals ; Arsenic* ; Humans ; Lethal Dose 50 ; Lipid Peroxidation ; Liver ; Male ; Mice* ; Mice, Inbred ICR ; Oxidative Stress ; Rats* ; Rats, Sprague-Dawley ; Sodium

Brain damage resulting from perinatal cerebral hypoxia and ischemia is a major cause of acute mortality and neurological disabilities, including cerebral palsy (CP) and cognitive dysfunction. In order to establish an experimental hypoxia-ischemia (HI) model of CP for the screening of therapeutics, we operated bilateral common carotid artery ligation (BCAO) and monolateral carotid artery occlusion (MCAO), followed by 15 min of hypoxia (8% oxygen) in 4-day-old rats, and evaluated neurobehavioral disorders. After surgery, the survival rates of male and female BCAO rats were 33.3 and 7.1%, respectively, whereas 100% and 82.4% MCAO rats survived. In neurobehavioral performances, both male and female BCAO rats showed delayed achievement of righting reflex, in contrast to a negligible effect in MACO animals. However, both BCAO and MCAO rats exhibited impairment of cliff avoidance performances, although the physical dysfunction was more severe in BCAO than in MCAO. In global locomotor activity, MCAO rats also displayed decreased fast-moving time comparable BCAO animals, and increased resting and slow-moving times. In addition, MCAO rats showed marked learning and memory deficit in passive avoidance performances, similar to BCAO animals. From immunostaining analyses, severe degradation and loss of myelin basic proteins were observed in the brain of BCAO rats, in contrast to a mild aggregation in MCAO animals. Therefore, it is suggested that MCAO should be a more suitable CP model than BCAO, based on the high survival rate, relatively-mild brain injury, and enough neurobehavioral disorders for the research on preventive and therapeutic compounds.
Achievement ; Animals ; Anoxia ; Brain ; Brain Injuries ; Carotid Arteries ; Carotid Artery, Common ; Cerebral Palsy ; Demyelinating Diseases ; Female ; Humans ; Hypoxia, Brain ; Infant ; Ischemia ; Learning ; Ligation ; Male ; Mass Screening ; Memory Disorders ; Models, Theoretical ; Motor Activity ; Myelin Basic Protein ; Rats ; Reflex, Righting ; Survival Rate