Effects of microsomal enzyme induction on the toxicity of pyrrolizidine (Senecio) alkaloids.

Abstract

Effects of microsomal enzyme induction by phenobarbital (PB) injection (ip) and ingestion of Eucalyptus globulus foliage or phenothiazine (PT) on the toxicity of pyrrolizidine alkaloids (PA) or dried plant material of Senecio longilobus (SL) and Senecio jacobaea (SJ) were evaluated in rats. The oral median lethal doses (LD50) for a PA mixture extracted from SL at 72, 144, and 168 h post PA administration were approximately greater than 320, 190, and 160 mg/kg, respectively. Induction of mixed-function oxidase (MFO) activity by PB or dietary eucalyptus leaves resulted in only a marginal effect on the acute LD50, with no effective change at 168 h. The LD50 values at 72, 144, and 168 h for PB-treated rats were approximately 320, 190, and 160 mg/kg, and for eucalyptus treated rats approximately 127, 133, and 133 mg/kg, respectively. Dietary PT did not alter the toxicity of SJ but did cause reductions in feed intake and average daily gain. Supplemental cysteine increased (p less than 0.05) survival time in SJ-consuming rats, with a concomitant increase (p less than 0.05) in SJ ingestion, and caused slight increases in average daily gain. The simultaneous addition of cysteine and PT to an SJ-containing diet resulted in an increased (p less than 0.05) survival time over SJ and SJ + PT diet groups and a slight decrease in survival time compared to the SJ + cysteine group.