Recently, natural products derived from AZD8055 plant extracts and their synthetic derivatives have been used to treat a wide range of respiratory diseases due to their anti-inflammatory and antioxidative properties. In

this line, oleanolic acid (OA), a triterpenoid compound present in a great variety of plants and food products (Liu, 2005), modulates the production and activity of pro-inflammatory cytokines and enzymatic antioxidant defence, as well as protects from oxidant stress by activating Nrf2 (Reisman et al., 2009, Takada et al., 2010 and Wang et al., 2010). Chemical synthesis of oleanolic acid has provided many useful derivatives that are more potent and specific than natural parent structures (Honda et al., 1997). Reddy et al. demonstrated

that intermittent administration of a synthetic triterpenoid compound, Navitoclax CDDO-imidazole (CDDO-Im) (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole, during exposure to hyperoxia confers protection against the development of ALI in mice (Reddy et al., 2009). However, the effects of oleanolic acid derivatives and triterpene derivatives are not necessarily similar to those of their parent molecules (Honda et al., 1998 and Honda et al., 1999). Additionally, even though the biological activity of oleanolic acid is lower than that of its derivatives, it is known to be relatively non-toxic (Liu, 1995 and Liu, 2005). We tested the hypothesis that oleanolic acid may curtail the inflammatory process, improving lung morphology and function in experimental ALI induced by paraquat. This study was approved by the Health Sciences Centre Ethics Committee at the Federal University of Rio de Janeiro. All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by

the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the National Academy of Sciences, USA. One hundred and eight BALB/c male mice (20–25 g) were kept under specific pathogen-free conditions in the Laboratory of Thiamet G Pulmonary Investigation animal care facility. All animals were randomly assigned to two groups. In the control group (C), mice received saline intraperitoneally (50 μL, ip), while in the ALI group paraquat (25 mg/kg, ip) was administered. Both groups were further treated with saline [ALI-SAL (0.1 mL, ip)], oleanolic acid [ALI-OA (10 mg/kg, ip)] or dexamethasone [ALI-DEXA (1 mg/kg, ip)] ( Göcgeldi et al., 2008) 1 h after paraquat or saline injection, in randomized order. For the present ALI model, different doses of OA (5, 10, and 20 mg/kg animal body weight) were titrated in pilot studies, and the 10 mg/kg dose was chosen based on the lowest mortality rate and lung morphofunction impairment. Thirty-six mice (n = 6/each) were used to evaluate lung mechanics and histology, as well as molecular biology.