TRPV1 Contributes to Cerebral Malaria Severity and Mortality by Regulating Brain Inflammation

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is a Ca+2-permeable channel expressed on neuronal and nonneuronal cells, known as an oxidative stress sensor. It plays a protective role in bacterial infection, and recent findings indicate that this receptor modulates monocyte populations in mice with malaria; however, its role in cerebral malaria progression and outcome is unclear. By using TRPV1 wild-type (WT) and knockout (KO) mice, the importance of TRPV1 to this cerebral syndrome was investigated. Infection with Plasmodium berghei ANKA decreased TRPV1 expression in the brain. Mice lacking TRPV1 were protected against Plasmodium-induced mortality and morbidity, a response that was associated with less cerebral swelling, modulation of the brain expression of endothelial tight-junction markers (junctional adhesion molecule A and claudin-5), increased oxidative stress (via inhibition of catalase activity and increased levels of H2O2, nitrotyrosine, and carbonyl residues), and diminished production of cytokines. Plasmodium load was not significantly affected by TRPV1 ablation. Repeated subcutaneous administration of the selective TRPV1 antagonist SB366791 after malaria induction increased TRPV1 expression in the brain tissue and enhanced mouse survival. These data indicate that TRPV1 channels contribute to the development and outcome of cerebral malaria.

Metformin disrupts insulin secretion, causes proapoptotic and oxidative effects in rat pancreatic beta‐cells in vitro

“…The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were analyzed in INS-1E cells after 48 h exposure to metformin and assayed as previously described by Pereira et al (2019). [33] Cells were homogenized in Tris-HCl buffer and stored at −80°C until processed.…”

“…The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were analyzed in INS-1E cells after 48 h exposure to metformin and assayed as previously described by Pereira et al (2019). [33] Cells were homogenized in Tris-HCl buffer and stored at −80°C until processed. The enzyme activity values were standardized by total protein values, as determined by the Pierce 660 nm Protein Assay Reagent (Thermo Fisher) and using bovine serum albumin as standard (Thermo Fisher).…”

Mediterranean Diet: Lipids, Inflammation, and Malaria Infection

“…The TRPV1 knockout (KO) exhibited lower concentrations of plasma and brain cytokines, especially TNF-α and IL-6, less cerebral swelling with higher levels of junctional adhesion molecule A, and claudin-5, in their brain vasculature. The TRPV1 KO mice presented less neuronal damage, and they were protected against Plasmodium-induced mortality and morbidity, but the Plasmodium load was not affected [ 91 ].…”