Bothrops pauloensis snake venom-derived Asp-49 and Lys-49 phospholipases A2 mediates acute kidney injury by oxidative stress and release of inflammatory cytokines

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Marinho, Aline Diogo ^{[1, 2]} ; de Moraes Silveira, Joao Alison ^{[1, 2]} ; Maia Chaves Filho, Adriano Jose ^{[1, 2]} ; Coelho Jorge, Antonio Rafael ^{[1, 2]} ; Nogueira Junior, Francisco Assis ^{[1, 2]} ; Magalhaes Pereira, Venucia Bruna ^{[1, 2]} ; Alexandre de Aquino, Pedro Everson ^{[1, 2]} ; Souza Pereira, Cassia Arruda ^[3] ; Azul Monteiro Evangelista, Janaina Serra ^[4] ; Macedo, Danielle Silveira ^{[1, 2]} ; Pereira Lima Junior, Roberto Cesar ^{[1, 2]} ; Toyama, Marcos Hikari ^[5] ; Bezerra Jorge, Roberta Jeane ^{[1, 2]} ; Silva Pereira, Gustavo Jose ^[3] ; Azul Monteiro, Helena Serra ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Ceara, Sch Med, Dept Physiol & Pharmacol, Coronel Nunes Melo St 1127, BR-60430275 Fortaleza, Ceara - Brazil

^[2] Univ Fed Ceara, Drug Res & Dev Ctr NPDM, Coronel Nunes Melo St 1000, BR-60430275 Fortaleza, Ceara - Brazil

^[3] Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, Tres Maio St 100, BR-04044020 Sao Paulo, SP - Brazil

^[4] Univ Estadual Ceara, Sch Vet, Postgrad Program Vet Sci, Fortaleza, Ceara - Brazil

^[5] Sao Paulo State Univ UNESP, Dept Biol & Environm Sci, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 190, p. 31-38, JAN 30 2021.
• Citações Web of Science: 0

Resumo

The envenomation caused by the Bothrops pauloensis snake leads to severe local and systemic effects including acute kidney injury. In this study, we investigated the renal effects by phospholipases A2 (PLA2s), divided into two main subgroups, Asp-49 and Lys-49, isolated from the Bothrops pauloensis snake venom (BpV) in isolated rat kidney system. Both PLA2s (3 mu g/mL), added alone to the perfusion system and analyzed for 120 min, had significant effects on isolated rat kidney. Asp-49 reduced Glomerular Filtration Rate (GFR) at 60, 90 and 120 min, and the percentage of total tubular sodium transport (%TN+) and potassium transport (%TK+) at 120 min. Lys-49 increased Perfusion Pressure (PP) at 120 min and reduced GFR, %TNa+ and the percentage of total tubular chloride transport (%TCl-) at 60, 90 and 120 min. Cytokine release in the kidney tissues were increased with Asp-49 PLA2 (IL-10) and Lys-49 PLA2 (TNF-alpha, IL-1 beta, IL-10). Both increased MPO activity. Asp-49 PLA2 decreased Glutathione (GSH) and increased nitrite levels, while Lys-49 PLA2 increased Malondialdehyde (MDA), GSH and nitrite levels. Histological analysis of the perfused kidneys revealed the presence of glomerular degeneration and atrophy, deposit of proteinaceous material in Bowman's space and intratubular with both PLA2s. These findings indicated that both PLA2s modified the functional parameters in an isolated perfused kidney model with increased oxidative stress and cytokine release. PLA2s are one of the components at high concentration in BpV and our results provide important knowledge about their involvement with the nephrotoxic mechanism. (AU)

• Processo FAPESP: 17/10863-7 - Estudo da lipofagia mediada pelos receptores two-pore channels
• Beneficiário: Gustavo José da Silva Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Regular