Hepatic injury associated with Trypanosoma cruzi infection is attenuated by treatment with 15-deoxy-Δ12,14prostaglandin J2.
Trypanosoma cruzi, the etiological agent of Chagas' disease, causes an intense inflammatory response in several tissues, including the liver. Since this organ is central to metabolism, its infection may be reflected in the outcome of the disease. 15-deoxy-Δ12,14prostaglandin J2(15dPGJ2), a natural agonist of peroxisome-proliferator activated receptor (PPAR) γ, has been shown to exert anti-inflammatory effects in the heart upon T. cruzi infection. However, its role in the restoration of liver function and reduction of liver inflammation has not been studied yet. BALB/c mice were infected with T. cruzi. The effects of in vivo treatment with 15dPGJ2 on liver inflammation and fibrosis, as well as on the GOT/GPT ratio were studied and the role of NF-κB pathway on 15dPGJ2-mediated effects was analysed. 15dPGJ2 reduced liver inflammatory infiltrates, proinflammatory enzymes and cytokines expression, restored the De Ritis ratio values to normal, reduced the deposits of interstitial and perisinusoidal collagen, reduced the expression of the pro-fibrotic cytokines and inhibited the translocation of the p65 NF-κB subunit to the nucleus. Thus, we showed that 15dPGJ2 is able to significantly reduce the inflammatory response and fibrosis and reduced enzyme markers of liver damage in mice infected with T. cruzi.
Instituto de Investigaciones en Microbiología y Parasitología Médica, Facultad de Medicina, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Federico Nicolás
FN
Penas
Instituto de Investigaciones en Microbiología y Parasitología Médica, Facultad de Medicina, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Ágata Carolina
ÁC
Cevey
Instituto de Investigaciones en Microbiología y Parasitología Médica, Facultad de Medicina, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Sofía
S
Siffo
Instituto de Investigaciones en Microbiología y Parasitología Médica, Facultad de Medicina, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Gerardo Ariel
GA
Mirkin
Instituto de Investigaciones en Microbiología y Parasitología Médica, Facultad de Medicina, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina. Electronic address: ngoren@fmed.uba.ar.
Nora Beatriz
NB
Goren
D000818:Animals; D015415:Biomarkers; D014355:Chagas Disease / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000187:drug effects; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics; D007155:Immunologic Factors / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D059208:Parasite Load; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015800:Protozoan Proteins / Q000032:analysis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014349:Trypanosoma cruzi / Q000235:genetics / Q000502:physiology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D015415:Biomarkers; D016207:Cytokines; D016054:DNA, Protozoan; D007155:Immunologic Factors; D016328:NF-kappa B; D047495:PPAR gamma; D015800:Protozoan Proteins; D015230:Prostaglandin D2
15-Deoxi-Δ(12-14) prostaglandine J2; Inflammation; Liver; PPARγ; Trypanosoma cruzi