Involvement of Inflammatory Cytokines, Renal NaPi-IIa Cotransporter, and TRAIL Induced-Apoptosis in Experimental Malaria-Associated Acute Kidney Injury

• Published in: Pathogens (Basel) Vol. 13; no. 5; p. 376
• Main Authors: Simião, Gustavo Martins, Parreira, Kleber Simônio, Klein, Sandra Gabriela, Ferreira, Flávia Batista, Freitas, Fernanda de Souza, Silva, Eduardo Ferreira da, Silva, Neide Maria, Silva, Murilo Vieira da, Lima, Wânia Rezende
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.05.2024
• Subjects: Acute renal failure; Alcohol; Animal models; Animals; Apoptosis; Biomarkers; Blood; Carrier proteins; Coma; Complications and side effects; Creatinine; cytokine; Cytokines; Development and progression; Down-regulation; Gene expression; Health aspects; Hypophosphatemia; Immunofluorescence; Immunoglobulin G; Infections; Inflammation; kidney; Kidneys; Malaria; Mortality; Nephritis; Parasites; Pathogenesis; Renal function; Risk factors; Therapeutic targets; Tumor necrosis factor; Tumor necrosis factor-α; Urea; Vector-borne diseases; Brazil; South America; Asia; cytokine; kidney; apoptosis; malaria
• ISSN: 2076-0817; 2076-0817
• DOI: 10.3390/pathogens13050376

The murine model of experimental cerebral malaria (ECM) induced by ANKA was used to investigate the relationship among pro-inflammatory cytokines, alterations in renal function biomarkers, and the induction of the TRAIL apoptosis pathway during malaria-associated acute kidney injury (AKI). Renal function was evaluated through the measurement of plasma creatinine and blood urea nitrogen (BUN). The mRNA expression of several cytokines and NaPi-IIa was quantified. Kidney sections were examined and cytokine levels were assessed using cytometric bead array (CBA) assays. The presence of glomerular IgG deposits and apoptosis-related proteins were investigated using in situ immunofluorescence assays and quantitative real-time PCR, respectively. NaPi-IIa downregulation in the kidneys provided novel insights into the pathogenesis of hypophosphatemia during CM. Histopathological analysis revealed characteristic features of severe malaria-associated nephritis, including glomerular collapse and tubular alterations. Pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, were upregulated. The TRAIL apoptosis pathway was significantly activated, implicating its role in renal apoptosis. The observed alterations in renal biomarkers and the downregulation of NaPi-IIa shed light on potential mechanisms contributing to renal dysfunction in ECM. The intricate balance between pro- and anti-inflammatory cytokines, along with the activation of the TRAIL apoptosis pathway, highlights the complexity of malaria-associated AKI and provides new therapeutic targets.