Alpha-tocopherol succinate does not mitigate nitrofurantoin-induced changes in the glutathione and protein thiol status of the isolated perfused rat liver.
Because it had been suggested that alpha-tocopherol might protect protein thiols (PSH) from oxidation, we were interested in determining if alpha-tocopherol could prevent or mitigate nitrofurantoin-induced changes in the glutathione (GSH) or PSH status of the liver. Isolated rat livers were perfused in the single pass mode for 310 min with Krebs-Henseleit buffer or the same buffer containing 25 nmol/ml of alpha-tocopherol succinate. Treated livers were exposed to 1200 nmol/ml of nitrofurantoin from 30 to 90 min. In control (no nitrofurantoin or alpha-tocopherol) livers, tissue levels of GSH and PSH were maintained at 78 +/- 6% and 94 +/- 6% of their initial values, but alpha-tocopherol levels declined from 34.9 +/- 0.6 nmol/g to 26 +/- 1.5 nmol/g. In the nitrofurantoin-only livers, GSH and PSH tissue levels fell to 17 +/- 10% and 49 +/- 6% of their initial levels (P less than 0.05, vs. controls), alpha-Tocopherol levels fell from 31.7 +/- 4.8 nmol/g to 17.0 +/- 2.8 nmol/g. In the alpha-tocopherol-supplemented, nitrofurantoin-treated livers, initial tissue levels of alpha-tocopherol were elevated to 43.8 +/- 1.4 nmol/g (P less than 0.05), but fell to 26.1 +/- 4.2 nmol/g. Their GSH and PSH tissue levels also declined to 7 +/- 3% and 56 +/- 8% of their initial values (P less than 0.05, vs. controls). Thus, it appeared that alpha-tocopherol supplementation was unable to prevent nitrofurantoin-induced changes in the GSH or PSH status of the liver.
Hoener
B
B
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
Hjalmarson
A C
AC
D000818:Animals; D005978:Glutathione / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D009582:Nitrofurantoin / Q000633:toxicity*; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000032:analysis / Q000378:metabolism*; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology
D013438:Sulfhydryl Compounds; D014810:Vitamin E; D009582:Nitrofurantoin; D005978:Glutathione; D024505:Tocopherols