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Oral Administration of GW788388, an Inhibitor of Transforming Growth Factor Beta Signaling, Prevents Heart Fibrosis in Chagas Disease

Figure 6

GW788388 administration at 20 dpi protected T. cruzi-infected mice from death and decreased heart fibrosis.

Male Swiss mice were injected IP with or without (NI) 104 bloodstream trypomastigotes. Then GW788388 (3 mg/kg) (Y GW788388) or DMSO (Y DMSO) was administered by gavage at 20 dpi. (A) Percent survival was monitored during the experiment until 24 dpi (Inset shows a blow-up of the survival curve from 20 to 24 dpi (100 represents the percentage of survival calculated from 20 dpi)). (B, C, D, E) Untreated infected mice were sacrificed at 15 dpi (B), 20 dpi (C), 24 dpi (D) and GW788388-treated mice at 20 dpi were sacrificed at 24 dpi (E). Heart sections were stained for collagen deposition by Masson's trichrome (light blue staining, open arrows). (F) 20 µg of total proteins from hearts at 24 dpi were resolved in 12% SDS/PAGE and immunoblotted with anti-collagen type I antibody and reprobed with anti-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) antibody. (G) Densitometric histograms of the normalized levels of collagen type I as related to GAPDH are shown. Values that were significantly different from studied groups are indicated by asterisks (**p<0.01 and * p<0.05). n = 4 mice/group in 3 independent experiments.

Figure 6

doi: https://doi.org/10.1371/journal.pntd.0001696.g006