ARSENIC-INDUCED STEATOSIS IN C57BL/6J MALE MICE CHRONICALLY EXPOSED THROUGH DRINKING WATER.

Vigo, Jaime B.; Ellzey, Joanne T.; Baker, Thomas P.; Bader, Julia O.; Oliver, Thomas G.

Epidemiological evidence suggests that chronic ingestion of arsenic through drinking water may have links with the onset of diabetes mellitus-Type 2. This investigation used an in vivo experimental setting to test the hypothesis that chronic ingestion of arsenic through the drinking water may induce diabetogenic effects in a mouse model fed with a low fat or a high fat diet. Four groups of C57BL/6J male mice (n=15/group) were fed with 4.5% (low) or 11% (high) fat diet, and exposed to drinking water containing 0 ppm or 22.5 ppm of sodium arsenite [As (III)] for 40 weeks. During the last 10 weeks, the fat content of the 11% fat diet groups was increased to 24% to accelerate increase in weight gain and to ensure reaching the obesity threshold (=50 g) within the experimental timeline. Light and transmission electron microscopy studies revealed an arsenic-induced hepatic steatosis and inflammation in the As (III)-exposed low fat group compared to the control low-fat group. A similar diet-induced hepatic steatosis and inflammation were also observed in both of the high fat diet groups with no significantly different pathology observed between the arsenic-exposed and control groups. A significant diet-induced increase in the average accumulated weights starting at week 6 (diet by week interaction p<0.001) and blood glucose of the groups fed with the high fat diet (p<0.001) compared to the low fat diet groups were observed. Terminal blood insulin showed a significant diet-induced increase for the high fat fed groups compared to the low fat fed groups (p=0.02). The organ to body weight ratio showed a significant diet effect for the liver (p<0.001), a significant diet effect (p=0.005) and a significant group effect (p=0.03) for the kidney, and a significant diet effect (p=0.01) for pancreas. There were significant group*diet*week interactions in both the amount of average water consumption and average cumulative food consumption. No significant differences were found for BUN. In conclusion, 40 weeks of exposure of C57BL/6J mice to 22.5 ppm of As (III) through drinking water did not provide evidence of diabetogenic effects but did provide evidence of steatosis in lean mice due to arsenic toxicity.

ARSENIC compounds; FATTY degeneration; MICE; INFLAMMATION; FIBROSIS; DRINKING water; ELECTRON microscopy

Texas Journal of Microscopy, 2007, Vol 38, Issue 2, p117

1554-0820

Academic Journal