The effect of BCNU (carmustine) on tissue glutathione reductase activity

A single, 50 mg/kg i.p. dose of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) to mice significantly inhibited glutathione reductase activity in liver within 10 min, and in lung and heart within 30 min. Maximal inhibition was reached at 4 h in all tissues and glutathione reductase activity remained significantly depressed for 48 h in liver and for 96 h in lung and heart. BCNU doses of less than 25 mg/kg had no effect on glutathione reductase activity. Increasing the BCNU dose to 100 mg/kg caused greater inhibition of glutathione reductase activity in all tissues. In spite of significantly decreased glutathione reductase activity, reduced glutathione (GSH) levels were unaffected in all tissues both 1 and 24 h after 50 mg/kg BNCU. These results suggest that lower than normal glutathione reductase activity is sufficient to maintain GSH levels. These results also demonstrate that BCNU inhibits tissue glutathione reductase activity for several days, but only at doses significantly greater than previously reported.