Influence of phenobarbital pretreatment on methoxyflurane and sodium fluoride nephropathy in Fischer 344 rats

Adult male Fischer 344 rats were used to investigate the effect of phenobarbital on methoxyflurane- and sodium fluoride-induced nephropathy. Pretreatment consisted of the ip administration of phenobarbital sodium at a dose of 50 mg/kg/day for 5 days; control animals were given saline. Pretreated animals were exposed to anesthetic concentrations of methoxyflurane during a period of 2 or 4 hr, whereas other pretreated animals were exposed only to oxygen, the methoxyflurane carrier gas. For comparative purposes, other pretreated animals received sodium fluoride in saline at doses of 0, 4.2 and 8.4 mg/300g. The results show that phenobarbital pretreatment enhances the nephrotoxicity of methoxy-flurance as evidenced by a significant interaction between phenobarbital and methoxyflurane on plasma concentrations of sodium and potassium, urinary volume, urinary excretion of urea, and urinary concentration test. In contrast, the nephrotoxicity of sodium fluoride was not affected by phenobarbital. These results provide good evidence that the urinary concentration test is a reliable monitor of the potentiating effect of phenobarbital on methoxyflurane nephrotoxicity.