ARS | Publication request: High Dietary Intake of Sodium Selenite Does Not Affect Gene Mutation Frequency in Rat Colon and Liver

Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 12, 2009
Publication Date: March 5, 2009
Citation: Zeng, H., Uthus, E.O., Ross, S., Davis, C.D. 2009. High Dietary Intake of Sodium Selenite Does Not Affect Gene Mutation Frequency in Rat Colon and Liver. Biological Trace Element Research. DOI 10.0017/s/12011-009-8348-3. Available: http://www.springerlink.com/humana+press/biochemistry.journal/12011.

Interpretive Summary: Previously we reported that both selenium deficiency and copper deficiency decreased plasma homocysteine (a cardiovascular risk marker) and increased plasma glutathione (an antioxidant compound) in rats. We also showed that the enzyme needed to synthesize glutathione in the liver was elevated in selenium deficiency as well as in copper deficiency. We suggested that in both deficiencies, that homocysteine (which is needed for the synthesis of glutathione) was diverted largely to the synthesis of glutathione because of the elevation of that liver enzyme. Because both selenium deficiency and copper deficiency had similar effects, we hypothesized that a combined deficiency would exacerbate the decrease in homocysteine and the increase in glutathione. In an experiment using rats we showed that a combined deficiency of both selenium and copper does indeed result in lower homocysteine and elevated glutathione. This may have implications in oxidative defense as both selenium and copper, through antioxidant enzymes, play major roles in defense against oxidative damage.

Technical Abstract: Previously we reported that both Se deficiency and Cu deficiency decreased plasma homocysteine (pHcys) and increased plasma glutathione (pGSH) in rats. We also showed that the catalytic subunit of glutamate-cysteine ligase (Gclc), which catalyzes the rate limiting step in glutathione biosynthesis, was upregulated in Se deficiency as well as in Cu deficiency. We suggested that in both deficiencies, that Hcys was being shunted through the transsulfuration pathway as a result of this up-regulation. Because both Se deficiency and Cu deficiency have similar effects, we hypothesized that a combined deficiency would exacerbate the decrease in pHcys and the increase in pGSH by further up-regulating Gclc. In a 2 x 2 experiment, male weanling Sprague-Dawley rats (N=8-10/group) were fed an amino acid-based diet containing either 0 or 0.2 µg Se (as selenite)/g and <1 or 6 µg Cu (as Cu carbonate)/g for 5 wk. Our findings show that a combined deficiency of both Se and Cu results in lower pHcys and significantly elevated pGSH. However, the up-regulation of liver Gclc alone, can not explain why rats fed the doubly-deficient diet have the lowest pHcys and the highest pGSH.