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Open AccessArticle

Effect of Artesunate on Leishmania Amazonesis Induced Neuroinflammation and Nociceptive Behavior in Male Balb/C Mice

1
University of Messina, Department of Chemical, Biological, Pharmaceutical and Environmental Science, 98155 Messina, Italy
2
Department of Health Sciences, University of Catanzaro "Magna Graecia", 88100 Catanzaro, Italy
3
Department of Veterinary Science, University of Messina, 98168 Messina, Italy
*
Authors to whom correspondence should be addressed.
The authors equally contributed to this work
Animals 2020, 10(4), 557; https://doi.org/10.3390/ani10040557 (registering DOI)
Received: 13 February 2020 / Revised: 21 March 2020 / Accepted: 25 March 2020 / Published: 27 March 2020
(This article belongs to the Section Animal Physiology)
Leishmaniasis is a multisystemic zoonotic disease with several symptoms, and treating this disease is a great challenge for veterinary medicine. Artemisinin derivatives are currently the most widely used drugs for the treatment of malaria, especially for their excellent safety profile and low cost. Artesunate is a more stable derivative of its precursor, artemisin, and has been shown to be a pluripotent agent with different pharmacological actions. In this study, we evaluated the role of neuroinflammation in leishmaniasis and its correlation with pain and sickness behavior, and the anti-inflammatory and neuroprotective effects of artesunate in a murine model of Leishmania amazonensis infection in BALB/c mice. The results from this study indicate that artesunate is a good candidate for treatment and/or as an adjuvant in anti- leishmaniasis therapy, and for preventing and alleviating leishmaniasis-induced pain and neuroinflammation.
Background: Leishmaniasis is a multisystemic zoonotic disease with several symptoms, including neurological disorders. Leishmaniasis is accompanied by an increase in nociceptive behaviors, linked to the presence of a chronic inflammatory state, in both peripheral tissue and the central nervous system. Artesunate is a more stable derivative of its precursor artemisin and has been shown to be a pluripotent agent with different pharmacological actions. Methods: In this study, we investigated the effects of artesunate in Leishmania amazonensi-infected BALB/c mice, evaluating its effectiveness in reducing inflammation, neuroinflammation, and nociceptive and sickness behaviors. Results: Our results demonstrate a significant increase in pain sensitivity and sickness behaviors after L. amazonensis infection. Moreover, the infection induced a significant increase in inflammatory response at both the paw and spinal cord level. Treatment with artesunate was able to induce a significant decrease in tissue inflammation and neuroinflammation and thus induce a significant decrease in pain sensitivity and sickness behaviors. Conclusions: The results from this study indicate that artesunate is a good candidate for treatment and/or as an adjuvant in leishmanicidal therapy, and to prevent and alleviate leishmaniasis-induced pain and neuroinflammation and thereby improve the quality of life of leishmaniasis patients.
Keywords: Leishmania amazonensis; inflammation; pain; murine model Leishmania amazonensis; inflammation; pain; murine model
MDPI and ACS Style

Gugliandolo, E.; Palma, E.; Peritore, A.F.; Siracusa, R.; D’Amico, R.; Fusco, R.; Licata, P.; Crupi, R. Effect of Artesunate on Leishmania Amazonesis Induced Neuroinflammation and Nociceptive Behavior in Male Balb/C Mice. Animals 2020, 10, 557.

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