Interleukin-1 Receptor-Induced Nitric Oxide Production in the Pancreas Controls Hyperglycemia Caused by Scorpion Envenomation

Autor(es)

Reis, Mouzarllem B. ^[1] ; Elias-Oliveira, Jefferson ^[1] ; Pastore, Marcella R. ^[1] ; Ramos, Simone G. ^[2] ; Gardinassi, Luiz G. ^[1] ; Faccioli, Lucia H. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Sao Paulo - Brazil

^[2] Fac Med Ribeirao Preto, Dept Patol & Med Legal, BR-14049900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 12, n. 3 MAR 2020.
• Citações Web of Science: 0

Resumo

Tityus serrulatus causes numerous scorpion envenomation accidents and deaths worldwide. The symptoms vary from local to systemic manifestations, culminating in pulmonary edema and cardiogenic shock. Among these events, transitory hyperglycemia is a severe manifestation that influences pulmonary edema, hemodynamic alterations, and cardiac disturbances. However, the molecular mechanism that leads to increased glucose levels after T. serrulatus envenomation remains unknown. This study aimed to investigate our hypothesis that hyperglycemia due to scorpion envenomation involves inflammatory signaling in the pancreas. The present study showed that T. serrulatus venom induces the production of IL-1 alpha and IL-1 beta in the pancreas, which signal via IL-1R and provoke nitric oxide (NO) production as well as edema in beta-cells in islets. Il1r1(-/-) mice were protected from transitory hyperglycemia and did not present disturbances in insulin levels in the serum. These results suggest that the pathway driven by IL-1 alpha/IL-1 beta-IL-1R-NO inhibits insulin release by beta-cells, which increases systemic glucose concentration during severe scorpion envenomation. A supportive therapy that inhibits NO production, combined with antiserum, may help to prevent fatal outcomes of scorpion envenomation. Our findings provide novel insights into the design of supportive therapy with NO inhibitors combined with antiscorpion venom serum to overcome fatal outcomes of scorpion envenomation. (AU)

• Processo FAPESP: 17/02314-3 - Investigação sobre alterações cardíacas que ocorrem no envenenamento pela peçonha do escorpião Tityus serrulatus
• Beneficiário: Mouzarllem Barros dos Reis
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/07125-6 - Novos aspectos funcionais dos eicosanóides
• Beneficiário: Lúcia Helena Faccioli
• Linha de fomento: Auxílio à Pesquisa - Temático