@MASTERSTHESIS{ 2019:893945840,
 	title = {Effect of Doxycycline in adult Schistosoma mansoni worms and on the development of experimental hepatic granulomatous inflammation},
 	year = {2019},
 	url = "https://bdtd.unifal-mg.edu.br:8443/handle/tede/1622",
 	abstract = "Schistosomiasis is a potential life threatening illness responsible for many deaths worldwide. This disease is more frequent in areas with low socioeconomic development and poor basic sanitation. Currently, the prevention and treatment of this disease is an important social-medical challenge, and the understanding of molecular and pharmacological aspects associated with the disease is fundamental for the development of more effective approaches to combat schistosomiasis. In this context, from in vitro and in vivo integrated models, we investigated the effect of doxycycline (Dx), a broad-spectrum antibiotic inhibitor of matrix metaloproteinases (MMPs), on adult Schistosoma mansoni worms and granulomatous liver inflammation in mice infected by this parasite. Adult S. mansoni worms in culture treated with different concentrations of Dx (50-180 μg/mL) were analyzed during 8 days to assess its morphology, eggs production, and mortality. Uninfected mice and those infected with S. mansoni, untreated and treated with praziquantel (Pz, 200 mg/kg, single dose) or Dx (50 mg/kg/day), were evaluated during 60 days. Our results indicated that Dx induced dose-dependent tegumentary lesions (bubbles, tubercle collapse, spicule disappearance, peeling, erosion, and contraction), reduced mating rate and eggs laying in adult S. mansoni worms. The effective dose for 50% of worms dead was reached at 112.0 μg/mL Dx (DL50). In mice, S. mansoni infection induced hepatomegaly, intense granulomatous inflammation and hepatic glycogen depletion. The number and size of granulomas was similar in untreated and Dx-treated animals. Untreated animals showed a predominance of productive granulomas, intense MMP-2 and MMP-9 activities. Dx-treated mice exhibited a significant increase in tissue inflammation, proportion of involutive granulomas, and hepatic colagenogenesis, as well as attenuated MMP-2 and MMP-9 activities. Our findings indicated that Dx is toxic to adult S. mansoni worms. However, in vitro beneficial effects were not reproduced in vivo, since Dx treatment increased liver granulomatous inflammation and colagenogenesis in S. mansoni-infected mice by a process potentially associated with Dx-mediated hepatic MMP-2 and MMP-9 inhibition.",
 	publisher = {Universidade Federal de Alfenas},
 	scholl = {Programa de Pós-graduação em Ciências Biológicas},
 	note = {Instituto de Ciências Exatas}
}