Effects of natural phenolic compounds from a desert dominant shrub Larrea divaricata Cav. on toxicity and survival in mice

Abstract

It is known that generalist herbivores may circumvent intoxication by ingesting small quantities from a mixture of plant secondary metabolites. However a single chemical, a highly toxic one or the most abundant in the mixture could cause toxicity. Survivorship and toxicity in Rockland male mice were measured to determine if the toxic effects of the phenolic resin of creosote bush (Larrea divaricata Cav.) is due to its major constituent, the nordihydroguaiaretic acid (NDGA) or to the total concentration of phenolic compounds in this resin. This objective was accomplished by exposing mice to voluntary feeding on resin-treated rat chow and by oral gavaging of mice with the following doses and compounds: Resin-100 mg (n = 7), NDGA-15 mg (n = 8), and NDGA-100 mg (n = 10) and Control (n = 6). Our hypothesis was that NDGA is responsible for the toxicity of Larrea divaricata's phenolic resin. Voluntary resin intake by mice had a pronounced toxic effect, producing body mass loss and significant reduction of food intake. Mice gavaged with Resin-100 mg, NDGA-100 mg, and NDGA-15 mg showed a significant reduction in survival probability compared to mice under Control conditions. Animáis exposed to NDGA-15 mg had a higher survivorship compared to the NDGA-100 mg animáis, and equivalent survivorship to the Resin-100 mg (containing 15 mg of NDGA) animáis. No significant differences in detoxification, measured as glucuronic acid conjugates in urine, were detected among gavage treatments. Therefore, given that just 15 mg of NDGA were enough to produce the same effect as the whole resin, we suggest that NDGA is the main constituent of Larrea divaricata's resin responsible for the toxic effect of the phenolic resin of this plant. © 2008 Sociedad de Biología de Chile.