Effect of buthionine sulfoximine on the response to arsenic deprivation in female rats

✍ Scribed by E.O. Uthus; Y.J. Kang

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 42 KB
• Volume: 11
• Category: Article
• ISSN: 0896-548X
• DOI: 10.1002/(sici)1520-670x(1998)11:1<29::aid-jtra4>3.0.co;2-z

✦ Synopsis

Arsenic has been proposed to have a physiological role in methionine metabolism, either in methionine recycling or in transsulfuration. Thus an experiment was designed to determine if a stressor of the transsulfuration pathway of methionine metabolism would affect arsenic deprivation. The stressor used was buthionine sulfoximine (BSO), 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 g arsenic/g and injected with 2.0 mmol BSO/kg body weight or 0.9% saline; arsenic was supplemented as As 2 O 3 . Injections were given twice per day for the last 7 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 the SAM/SAH ratio. BSO treatment did not have much of an effect on the response to arsenic deprivation, which suggests that arsenic has a physiological role more closely related to methionine recycling than to transsulfuration. J.