Doxycycline hyclate: A schistosomicidal agent in vitro with immunomodulatory potential on granulomatous inflammation in vivo
Autor: | Miriam Viviane Dias, Rômulo Dias Novaes, Camila Cabral Campos, Marcos José Marques, Reggiani Vilela Gonçalves, Aline Pereira Castro, Raquel Lopes Martins Souza, Thaiany G. Souza-Silva |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Immunology Inflammation Schistosomiasis Doxycycline Hyclate Praziquantel Microbiology Immunomodulation 03 medical and health sciences Antimalarials Mice Schistosomicides 0302 clinical medicine In vivo parasitic diseases medicine Immunology and Allergy Animals Humans Cells Cultured Pharmacology Granuloma biology Lethal dose Schistosoma mansoni biology.organism_classification medicine.disease In vitro Disease Models Animal 030104 developmental biology Liver Matrix Metalloproteinase 9 030220 oncology & carcinogenesis Doxycycline Infertility Matrix Metalloproteinase 2 Interleukin-4 medicine.symptom medicine.drug |
Zdroj: | International immunopharmacology. 70 |
ISSN: | 1878-1705 |
Popis: | We investigated the effect in vitro and in vivo of doxycycline hyclate (Dx), a broad-spectrum antibiotic inhibitor of matrix metaloproteinases (MMPs), on adult Schistosoma mansoni worms and granulomatous liver inflammation in infected mice. Adult S. mansoni worms in culture treated with different concentrations of Dx (50–180 μg/mL) were studied for eight 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) or Dx (50 mg/kg), were evaluated for 60 days. Our results indicated that Dx induced dose-dependent integumentary lesions (bubbles, tubercle collapse, spicule disappearance, peeling, and erosion), reduced mating rate and eggs-laying in adult S. mansoni worms. The effective lethal dose required to kill 50% of worms was 112.0 μg/mL Dx (DL50). In mice, S. mansoni infection induced hepatomegaly, intense IL-4, IL-10, TNF-α and TGF-β production, granulomatous inflammation and hepatic glycogen depletion. The number and size of the granulomas was similar in untreated and Dx-treated animals. Untreated animals showed a predominance of productive granulomas, and intense MMP-2 and MMP-9 activities. Dx-treated mice exhibited a significant increase in IL-4 levels, tissue inflammation, proportion of involutive granulomas, and hepatic collagenogenesis, as well as attenuated MMP-2 and MMP-9 activities. Our findings indicated that Dx is toxic to adult S. mansoni worms in vitro. However, in vitro beneficial effects were not reproduced in vivo, since Dx treatment increased liver granulomatous inflammation and collagenogenesis in S. mansoni-infected mice by a process potentially associated with Dx-mediated hepatic MMP-2 and MMP-9 inhibition. |
Databáze: | OpenAIRE |
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