cell biochemistry and function Cell Biochem Funct 2007; 25: 195–201. Published online 29 November 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1027/cbf.1307 Influence of indole acetic acid on antioxidant levels and enzyme activities of glucose metabolism in rat liver Diogo Luiz Oliveira, Silvana M. Piccoli Pugine, Mariana S. Larraz Ferreira, Patricia Goldshmidt Lins, Ernane J. Xavier Costa and Mariza Pires de Melo* Department of Basic Science, Faculty of Zootechny and Food Engineering (FZEA), University of Sa ˜o Paulo, Pirassununga, Brazil Indole acetic acid (IAA) is an auxin and can be synthesized in animals. This compound is metabolized in vitro by peroxidase, producing reactive oxygen species. The toxic effect of indole acetic acid in leukocytes is associated with peroxidase activities and these processes have been implicated in activation of glucose and glutamine metabolism. However, studies in vitro have shown that IAA, in absence of peroxidase, is an antioxidant almost as high in potency as those of other indolic compounds. The purpose of this study was to investigate the possible involvement of a toxic effect of indole acetic acid in the liver, as evidenced by oxidative stress and enzyme activities of the glucose pathway. The animals received IAA by subcutaneous or gavage administration in a phosphate buffered saline (the control group received only the phosphate buf- fered saline). The other groups received IAA at concentrations of 1 mg, 18 mg and 40 mg per kg of body mass per day. Treatments with 18 mg and 40 mg IAA decreased the activity of catalase by both subcutaneous (30% and 26%) or gavage administration (19% and 28%), respectively. A similar effect was observed on the activity of glutathione peroxidase of animals exposed to 18 mg and 40 mg IAA: A decrease of 34% and 29%, respectively, for subcutaneous administration and a decrease of 29% and 25%, respectively, for gavage administration. However, in neither source of administration did the acid alter superoxide dismutase, glutathione reductase and myeloperoxidase activities. Another alteration was observed in respect of reduced glutathione content in this organ. The lipid peroxidation level showed a significant decrease with subcutaneous (30%, 29% and 24%) and gavage administration (25%, 26% and 24%) using 1 mg, 18 mg and 40 mg of IAA, respectively compared with the control. The reduced glutathione content and catalase activity in the plasma were not altered by either of the two methods of administration. In addition to these findings, after subcutaneous or gavage admin- istration of IAA, the activities of hepatic enzymes of glucose metabolism were not affected (glucokinase, lactate dehydro- genase, glucose-6-phosphate dehydrogenase and citrate synthase). Evidence is presented herein that IAA did not have a pro- oxidant effect in the liver as deduced from a reduction of catalase and glutathione peroxidase activities, a decrease of lipid peroxidation content and no alteration of the pool of reduced glutathione. The effects of IAA were independent of the way of administration. Copyright # 2005 John Wiley & Sons, Ltd. key words — reactive oxygen species; superoxide dismutase; lipid peroxidation; catalase; peroxidase INTRODUCTION Indole acetic acid (IAA) is an important indolic compound and is a plant hormone, which can be synthesized in plants, microorganism and animals including mammals. It is present in human urine, 1 blood plasma 2 and the central nervous system. 3 Ani- mals obtain indole acetic acid from three sources: (i) a diet rich in vegetable stems; (ii) IAA produced by intestinal bacteria 4 ; and (iii) IAA synthesized from tryptophan in various tissues. 5 Recent studies showed that in vivo IAA administration could increase the phagocytic capacity of rat neutrophils 6 and other studies showed that this auxin could be used for targeted cancer therapy. 7–9 But one dose of IAA (higher than 100 mg of IAA per kg of body mass) is sufficient to promote myotonia in rats and cause a delay in relaxation of the soleus muscle in cats. 10 Indole acetic acid is metabolized by peroxidase 11 or by rat neutrophil homogenates 12 in vitro producing reactive oxygen species. The combination of IAA Received 5 July 2005 Revised 15 September 2005 Copyright # 2005 John Wiley & Sons, Ltd. Accepted 6 October 2005 *Correspondence to: Dr M. P. De Melo, Departamento de Cie ˆncias Ba ´sicas, FZEA, Universidade de Sa ˜o Paulo, Av. Duque de Caxias Norte, 225, 13635-000, Pirassununga, SP, Brasil. Fax: 55 19-3565 4117. E-mail: mpmelo@usp.br