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Effects of Oligoelements Se, Zn, and Mn plus Lachesis Muta Venom in Experimental Scleroderma

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Abstract

Scleroderma, sclerosis of the skin, is a severe autoimmune disease refractant to all kind of treatments. To study the in vivo effects of a combination of three oligoelements selenium (Se), zinc (Zn), and manganese (Mn) plus Lachesis muta venom (O-LM) on the bleomycin (BLM)-induced scleroderma mouse experimental model. C3H mice were randomly divided into four groups: control (phosphate-buffered saline (PBS)), O-LM, BLM, and BLM + O-LM. All administrations were performed subcutaneously into the back of mice. BLM was injected 5 days per week for three consecutive weeks and O-LM was administered simultaneously with BLM from the beginning of the experiments and lasted for 3 weeks after the final BLM or PBS injection (for O-LM and BLM + O-LM groups), when animals were sacrificed and histopathological, immunohistochemical, thiobarbituric acid reactive species (TBARS) evaluation, and autoantibodies detection were determined. O-LM significantly reduced BLM-induced enhanced dermal thickness (605 ± 47 vs. 956 ± 59 μm, P < 0.01), collagen deposition, and mast cells infiltration (43.1 ± 1.0 vs. 102 ± 14.1 mast cells, P < 0.05). O-LM administration significantly blocked BLM-induced oxidative damage and the enhanced immunoreactive fibroblasts for α-smooth muscle actin while reduced BLM-induced autoantibodies that strongly react mainly with skin and spleen. O-LM significantly reduced BLM-induced scleroderma through the modulation of antioxidant and immunological pathways.

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Acknowledgments

We dedicate this work to the memory of our friend, colleague, and excellent pathologist Maximo Croci, MD. We thank Alejandro Paredes for technical assistance. V. Medina, G. Martín, A. Genaro, G. Cremaschi and R. Bergoc are members of the National Research Council (CONICET).

Conflict of interest

Authors declared no conflict of interest.

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Authors and Affiliations

  1. Institute of Immunooncology, 3200 Córdoba Av., 1187, Buenos Aires, Argentina

    Ernesto J. V. Crescenti & Lorena A. Sambuco

  2. Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, 1113, Buenos Aires, Argentina

    Vanina A. Medina, Graciela P. Cricco, Gabriela A. Martín, Diego J. Martinel Lamas, Elena S. Rivera & Rosa M. Bergoc

  3. Neuroimmunomodulation and Molecular Oncology Division, Institute for Biomedical Research, Catholic University from Argentina (UCA), Buenos Aires, Argentina

    Graciela A. Cremaschi, Ana M. Genaro & Eduardo Valli

  4. National Research Council of Argentina (CONICET), Buenos Aires, Argentina

    Vanina A. Medina, Graciela A. Cremaschi, Ana M. Genaro, Gabriela A. Martín & Eduardo Valli

  5. Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

    Juan C. Perazzo

Authors
  1. Ernesto J. V. Crescenti
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  2. Vanina A. Medina
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  3. Lorena A. Sambuco
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  4. Graciela A. Cremaschi
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  5. Ana M. Genaro
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  6. Graciela P. Cricco
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  7. Gabriela A. Martín
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  8. Eduardo Valli
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  9. Diego J. Martinel Lamas
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  10. Juan C. Perazzo
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  11. Elena S. Rivera
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  12. Rosa M. Bergoc
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Corresponding authors

Correspondence to Vanina A. Medina or Rosa M. Bergoc.

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Crescenti, E.J.V., Medina, V.A., Sambuco, L.A. et al. Effects of Oligoelements Se, Zn, and Mn plus Lachesis Muta Venom in Experimental Scleroderma. Biol Trace Elem Res 157, 138–146 (2014). https://doi.org/10.1007/s12011-013-9876-4

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  • DOI: https://doi.org/10.1007/s12011-013-9876-4

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