Meeting Abstract

77.3  Friday, Jan. 7  Role of cytochrome P450s in juniper versus creosote consumption in woodrats SKOPEC, M.M.*; MALENKE, J.R.; HALPERT, J.R.; DEARING, M.D.; Weber State University; University of Utah; University of California, San Diego; University of Utah micheleskopec@weber.edu

Cytochrome P450s are a diverse array of enzymes thought to be important in the biotransformation of plant secondary compounds (PSC) present in the diets of mammalian herbivores. To examine the role of P450s in this process, we studied two closely related species of woodrats (Neotoma) that feed on diets with disparate PSC profiles. Neotoma lepida consumes juniper (Juniperous osteosperma), containing high levels of terpenes, whereas Neotoma bryanti consumes creosote (Larrea tridentata), containing high levels of phenolics. We hypothesized that these species use different detoxification pathways to metabolize PSCs in their diets. We used aminobenzotriazole (ABT) a suicide inhibitor of P450s to determine the relative role of P450s in metabolizing PSCs in the woodrats’ diets.Neotoma lepida were fed control diet and 50% juniper diet and N. bryanti were fed control diet and 4% creosote resin diet. Dry matter intake (DMI)was measured prior to and after the animals were dosed orally with 100mg/kg ABT. ABT inhibited DMI of all the diets but in a species and diet dependent manner. The ABT inhibited control diet DMI in the N. bryanti to a greater extent than in N. lepida (46% versus 19% DMI, p=0.014). There was no difference between species in the amount ABT inhibited the toxic diet DMIs (28% for creosote diet in N. bryanti and 35% for juniper diet in N. lepida, p=0.49). In N. lepida ABT had a greater effect on DMI of the juniper diet than the control diet (p=0.024), while in N. bryanti there was a trend for ABT to have a greater effect on DMI of the control diet than the creosote diet (p=0.098). We conclude that P450s are a more important pathway for the detoxification of PSCs present in juniper than creosote.