Effects of chronic dietary inorganic arsenic in dogs

Thirty female beagle dogs, 7 to 8 months old, were assigned to 5 groups. Control, low dosage, medium dosage, high dosage, and pair fed groups were offered 0, 1, 2, 4, and 0 mg per kg of body weight per day (mg/kg/day) of sodium arsenite respectively in their feed. On day 59 the dosage was doubled for the rest of the experiment which ended on day 183. The pair fed group was offered the amount of feed that the high dosage group consumed. Nominal dosages of 4 and 8 mg/kg/day caused significant decrease in feed consumption and body weight. Groups with decreased feed consumption early in the study gradually returned to normal food intake as the experiment progressed. Dogs offered 8 mg/kg/day did not fully compensate the lost feed intake. The linear regression of pair fed group body weight over time was not significantly different than that of high dosage group. This shows that dietary sodium arsenite caused a dose dependent decrease of feed intake and body weight. Weight loss was caused by decreased feed consumption not by direct effect of the sodium arsenite;No gross or light microscopic liver lesions were present in any group. Hepatocyte glycogen content was abundant and not significantly different among control, medium dosage, high dosage, and pair fed groups. Hepatocyte lipid content was limited and not different between control and high dosage groups. Electron microscopic evaluation of control and high dosage group livers was done. Hepatocyte mitochondrial volume density was increased in the treated group by 22 percent. Individual mitochondrial perimeters and maximum diameters were significantly increased in the treated group. Mitochondrial circularity shape factor was significantly decreased in treated animals. Stereological analysis indicated enlargement of heptocytic mitochondria in sodium arsenite fed dogs;Serum liver leakage enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were elevated in treated groups relative to controls. ALT and AST elevations relative to controls were persistent and low grade. Only ALT in the high dosage group was elevated above what is considered normal. Elevated serum levels of ALT and AST indicated sodium arsenite caused altered hepatocyte plasma membrane permeability