Inhibition of VEGF-Flk-1 binding induced profound biochemical alteration in the hippocampus of a rat model of BBB breakdown by spider venom. A preliminary assessment using FT-IR spectroscopy

Autor(es)

Rodrigues Mesquita-Britto, Maria Helena A. ^{[1, 2]} ; Padilha Mendonca, Monique Culturato ^{[1, 2]} ; Soares, Edilene Siqueira ^[1] ; Sakane, Kumiko Koibuchi ^[3] ; da Cruz-Hofling, Maria Alice ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas, SP - Brazil

^[3] Univ Vale Paraiba, Inst Res & Dev, Sao Jose Dos Campos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEUROCHEMISTRY INTERNATIONAL; v. 120, p. 64-74, NOV 2018.
• Citações Web of Science: 0

Resumo

Phoneutria nigriventer spider venom (PNV) contains ion channels-acting neuropeptides that in rat induces transitory blood-brain barrier breakdown (BBBb) in hippocampus in parallel with VEGF upregulation. We investigated whether VEGF has a neuroprotective role by inhibiting its binding to receptor Flk-1 by itraconazole (ITZ). FT-IR spectroscopy examined the biochemical status of hippocampus and evaluated BBBb in rats administered PNV or ITZ/PNV at periods with greatest toxicity (1-2h), recovery (5h) and visual absence of symptoms (24h), and compared to saline and ITZ controls. The antifungal treatment before venom intoxication aggravated the venom effects and increased BBB damage. FT-IR spectra of venom, hippocampi of controls, PNV and ITZ-PNV showed a 1400 cm(-1) band linked to symmetric stretch of carboxylate and 1467 cm(-1) band (CH2 bending: mainly lipids) that were considered biomarker and reference bands, respectively. Inhibition of VEGF/Flk-1 binding produced marked changes in lipid/protein stability at 1-2h. The largest differences were observed in spectra regions assigned to lipids, both symmetric (2852 cm(-1)) and asymmetric (2924 and 2968 cm-1). Quantitative analyses showed greatest increases in the 1400 cm(-1)/1467 cm(-1) ratio also at 1h. Such changes at period of rats' severe intoxication referred to wavenumber region from 3106 cm(-1) to 687 cm(-1) assigning for CH and N-H stretching of protein, Amide I, C=N cytosine, N-H adenine, Amide II, CH2 bending: mainly lipids, C-O stretch: glycogen, polysaccharides, glycolipids, z-type DNA, C-C, C-O and CH out-of-plane bending vibrations. We conclude that VEGF has a neuroprotective role and can be a therapeutic target in PNV envenomation. FT-IR spectroscopy showed to be instrumental for monitoring biochemical changes in this model of P. nigriventer venom-induced BBB disruption. (AU)

• Processo FAPESP: 05/53625-1 - Ação dos mastoparanos e da fosfolipase A2 isolados do veneno de Polybia paulista (Hymenoptera, Epiponini) nos mecanismos de apoptose e necrose de células musculares e mitocôndrias isoladas de camundongos Balb/c
• Beneficiário: Maria Alice da Cruz Hofling
• Modalidade de apoio: Auxílio à Pesquisa - Regular