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Evaluation of substance-P toxicity with single dose and repeated dose in rats

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Abstract

Toxicity study evaluating the effects of intravenous injection of SP with single- and repeated-dose in rats was performed. Single 100, 50, and 10 mg/kg doses of SP were administered and animals were monitored for 14 days. Although 10 mg/kg dose did not affect behavior and survival, 100 and 50 mg/kg doses elicited mortality, suggesting the minimum lethal dose (MLD) of SP to be between 10 and 50 mg/kg. To evaluate the toxicity of repeated dosing, rats were injected twice first two days per week with 30, 10, and 3 mg/kg of SP over 2 weeks and evaluated for survival, behavior, hematological factors, and organ weight. All rats administered with 10 and 3 mg/kg SP survived with minor changes in behavior and hematological indices. Thus, certain poison dose was estimated to be approximately 3 mg/kg, indicating that application of SP below 3mg/kg may not be associated with toxicity.

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References

  1. Rupniak, N. M. and Kramer, M. S. Discovery of the anti-depressant and anti-emetic efficacy of substance P re-ceptor (NK1) antagonists. Trends Pharmacological Sci 20:485–490 (1999).

    Article  CAS  Google Scholar 

  2. Nakamura, M. et al. Promotion of corneal epithelial wound healing in diabetic rats by the combination of a substance P-derived peptide (FGLM-NH2) and insulin-like growth factor-1. Diabetologia 46:839–842 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Hong, H. S. et al. A new role of substance P as an in-jury-inducible messenger for mobilization of CD29 (+ +) stromal-like cells. Nat Med 15:425–435 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. An, Y. S. et al. Substance P stimulates the recovery of bone marrow after the irradiation. J Cell Physiol 226: 1204–1213 (2011).

    Article  CAS  PubMed  Google Scholar 

  5. Kang, M. H., Kim, D. Y., Yi, J. Y. and Son, Y. Substan-ce-P accelerates intestinal tissue regeneration after gam-ma irradiation-induced damage. Wound Repair Regen 17:216–223 (2009).

    Article  PubMed  Google Scholar 

  6. Jiang, M. H. et al. Substance P induces M2-type macro-phages after spinal cord injury. Neuroreport 23:786–792 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Jiang, M. H. et al. Substance P reduces apoptotic cell death possibly by modulating the immune response at the early stage after spinal cord injury. NeuroReport 24:846–851 (2013).

    Article  CAS  PubMed  Google Scholar 

  8. Lee, J. Y. et al. Wound contraction decreases with in-travenously injected substance P in rabbits. Burns 40: 127–134 (2014).

    Article  PubMed  Google Scholar 

  9. Delgado, A. V., McManus, A. T. and Chambers, J. P. Exogenous administration of Substance P enhances wound healing in a novel skin-injury model. Exp Biol Med (Maywood) 230:271–280 (2005).

    CAS  Google Scholar 

  10. Kim, J. H., Jung, Y., Kim, B. S. and Kim, S. H., Stem cell recruitment, and angiogenesis of neuropeptide sub-stance P coupled with self-assembling peptide nanofi-ber in a mouse hind limb ischemia model. Biomaterials 34:1657–1668 (2013).

    Article  CAS  PubMed  Google Scholar 

  11. Hong, H. S. and Son, Y. Substance P ameliorates colla-gen II-induced arthritis in mice via suppression of the inflammatory response. Biochem Biophys Res Com-mun 453:179–184 (2014).

    Article  CAS  Google Scholar 

  12. Delgado, A. V., McManus, A. T. and Chambers, J. P. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuro-peptides 37:355–361 (2003).

    CAS  Google Scholar 

  13. Lighvani, S., Huang, X., Trivedi, P. P., Swanborg, R. H. and Hazlett, L. D. Substance P regulates natural killer cell interferon-c production and resistance to Pseudo-monas aeruginosa infection. Eur J Immunol 35:1567–1575 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Sun, J., Ramnath, R. D. and Bhatia, M. Neuropeptide substance P upregulates chemokine and chemokine re-ceptor expression in primary mouse neutrophils. Am J Physiol Cell Physiol 293:C696–704 (2007).

    Article  Google Scholar 

  15. Rameshwar, P., Ganea, D. and Gascón, P. In vitro stim-ulatory effect of substance P on hematopoiesis. Blood 81:391–398 (1993).

    CAS  PubMed  Google Scholar 

  16. Yang, C. M. et al. Substance P-induced activation of p42/44 mitogen-activated protein kinase associated with cell proliferation in human tracheal smooth muscle cells. Cell Signal 14:913–923 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Milner, P. et al. Regulation of substance P mRNA ex-pression in human dermal microvascular endothelial cells. Clin Exp Rheumatol 22:4–7 (2004).

    Google Scholar 

  18. Gallicchio, M. et al. Substance P-induced cyclooxy-genase-2 expression in human umbilical vein endoth-elial cells. Br J Pharmacol 147:681–689 (2006).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Ziche, M. et al. Substance P stimulates neovasculariza-tion in vivo and proliferation of cultured endothelial cells. Microvasc Res 40:264–278 (1990).

    Article  CAS  PubMed  Google Scholar 

  20. Salisbury, E. et al. Sensory Nerve Induced Inflamma-tion Contributes to Heterotopic Ossification. J Cell Biochem 112:2748–2758 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Hong, H. S., Um, J., Lee, Z. H. and Son, Y. Long-term comparative study of Substance-P with methylpredni-solone on the development of osteoporosis. J Toxicol Sci 39:391–399 (2014).

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Youngsook Son.

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Hong, H.S., Lim, S.V. & Son, Y. Evaluation of substance-P toxicity with single dose and repeated dose in rats. Mol. Cell. Toxicol. 11, 201–211 (2015). https://doi.org/10.1007/s13273-015-0019-1

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  • DOI: https://doi.org/10.1007/s13273-015-0019-1

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