GW0742

Cell experiment:

The PPARβ activator GW0742 and the RXR activator 9-cis-retinoic acid are dissolved in DMSO. The final DMSO concentration des not exceed 0.5% v/v, and this concentration is used in control wells. For each culture plate, one row of wells is treated with 500 μM glutamate. These wells serve as a positive control and for normalisation of data. Cell death (toxicity) is assessed by using an assay designed to measure lactate dehydrogenase (LDH) release[2].

Animal experiment:

Male CD mice (25-35 g) are housed in a controlled environment and provided with standard rodent chow and water. Mice are randomized into four experimental groups: bleomycin-treated group: mice are subjected to lung injury induced by intratracheal instillation of bleomycin and treated daily via intraperitoneal injection with vehicle of GW0742 (10% dimethylsulfoxide (OMSO, 1 mL/kg), 1 h after BLEO instillation (n = 15). GW0742 group: identical to bleomycin-treated group but mice are treated daily with GW0742 (0.3 mg/kg, 1h after BLEO instillation) via intraperitoneal injection (n = 15). Sham-operated mice + vehicle group: animals are subjected to the identical surgical procedure but receive intratracheal instillation of saline (0.9%) instead of BLEO and are treated daily with the vehicle of GW0742 (10% dimethylsulfoxide (DMSO), 1 mL/kg, i.p.), 1 h after saline instillation (n = 15). Sham-operated mice + GW0742 group: identical to sham + vehicle group but mice are treated daily with GW0742 (0.3 mg/kg, 1 h after saline instillation) via intraperitoneal injection (n = 15)[3].

References:

[1]. Sznaidman ML, et al. Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity. Bioorg Med Chem Lett. 2003 May 5;13(9):1517-21.
[2]. Smith SA, et al. Effect of the peroxisome proliferator-activated receptor beta activator GW0742 in rat cultured cerebellar granule neurons. J Neurosci Res. 2004 Jul 15;77(2):240-9.
[3]. Galuppo M, et al. GW0742, a high affinity PPAR-β/δ agonist reduces lung inflammation induced by bleomycin instillation in mice. Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):1033-46.
[4]. Kuo SC, et al. Activation of receptors δ (PPARδ) by agonist (GW0742) may enhance lipid metabolism in heart both in vivo and in vitro. Horm Metab Res. 2013 Nov;45(12):880-6.