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United States Department of Agriculture

Agricultural Research Service

Title: Effect of Buthionine Sulfoximine on the Response to Arsenic Deprivation in Female Rats

Authors
item Uthus, Eric
item Kang, Y - U NORTH DAKOTA

Submitted to: Journal of Trace Elements in Experimental Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 10, 1997
Publication Date: N/A

Interpretive Summary: Arsenic, in small amounts, is thought to have a biological role in the metabolism of the amino acid, methionine. The metabolism of methionine can follow either a pathway where the methionine molecule is used over and over (recycling pathway)or a pathway in which the methionine molecule is consumed. This study was designed to determine the biological role of arsenic in the pathway in which methionine is consumed. This was done, i laboratory rats fed a diet deficient in arsenic, by stressing this pathway with a compound called BSO. BSO inhibits an enzyme important in this pathway. The hypothesis of the experiment was, if arsenic is important in this degradative pathway of methionine, then BSO treatment would exacerbate the effects of arsenic deprivation. Many known effects of BSO were seen in the rats. Also, known signs of arsenic deprivation were seen. However, it was found the BSO treatment did not enhance these signs s of arsenic deprivation. It was thus concluded that arsenic does not have a direct role in the degradative pathway in methionine metabolism. Thus, it is likely that the biological role of arsenic is in the recycling pathway. Future studies will focus on this aspect of methionine metabolism. These studies will help ascertain the biological function of arsenic and will help determine the relative importance of arsenic in human nutriture.

Technical Abstract: Arsenic has been proposed to have a physiological role in methionine metabolism, either in methionine recycling or in transulfuration. Thus, an experiment was designed to determine if a stressor of the transulfuration pathway of methionine metabolism would affect arsenic deprivation. The stressor used was buthionine sulfoximine (BS) which inhibits the synthesis of glutathione (GSH), a cysteine containing tripeptide, serving as a major reserve of cysteine. In this experiment, the effect of GSH depletion on the response of rats to arsenic deprivation was determined. The experiment was factorially arranged and used four groups of nine female weanling Sprague-Dawley rats. The rats were fed a diet containing either 0 or 0.5 ug arsenic/g and injected with 2.0 mmol BSO/kg body weight or 0.9% saline. Injections were given twice per day for the last seven days of the experiment starting on day 70. BSO treatment significantly decreased the concentration of GSH in blood and liver, increased the specific activities of liver glutathione S-transferase and glutathione reductase, and decreased the specific activities of liver cystathionase and S-adenosylmethionine synthetase. In liver, arsenic deprivation increased the concentration of S-adenosylhomocysteine (SAH) and slightly decreased the concentration of S-adenosylmethionine (SAM); this resulted in a significant decrease in SAM/SAH ratio. BSO treatment did not have much of an effect on the response to arsenic deprivation; this suggests that arsenic has a physiological role more closely related to methionine recycling than to transsulfuration.

Last Modified: 7/24/2014
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