Cylindrospermopsin impairs tubular transport function in kidney cells LLC-PK1

Moraes, A.C.N.; Freire, Daniel Soares; Habibi, Hamid R.; Lowe, Jennifer; Magalhães, Valéria Freitas de

doi:10.1016/j.toxlet.2021.03.002

Cited by 7 publications

(2 citation statements)

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“…Megalin and cubilin mediate the uptake of serum albumin via endocytosis in renal proximal tubule cells [ 47 , 48 ]. Since megalin and cubilin are expressed in LLC-PK1 cells [ 49 , 50 ], it is hypothesized that S n -HSA transferred supersulfides via megalin or cubilin in this study. However, megalin and cubilin might not recognize poly-NAC-Sn-HSA as serum albumin because more than five lysine residues of HSA are modified.…”

Section: Discussionmentioning

confidence: 99%

Acute Kidney Injury Caused by Rhabdomyolysis Is Ameliorated by Serum Albumin-Based Supersulfide Donors through Antioxidative Pathways

Ikeda-Imafuku,

Fukuta,

Tuan Giam Chuang

et al. 2024

Pharmaceuticals

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Oxidative stress is responsible for the onset and progression of various kinds of diseases including rhabdomyolysis-induced acute kidney injury (AKI). Antioxidants are, therefore, thought to aid in the recovery of illnesses linked to oxidative stress. Supersulfide species have been shown to have substantial antioxidative activity; however, due to their limited bioavailability, few supersulfide donors have had their actions evaluated in vivo. In this study, human serum albumin (HSA) and N-acetyl-L-cysteine polysulfides (NACSn), which have polysulfides in an oxidized form, were conjugated to create a supersulfide donor. HSA is chosen to be a carrier of NACSn because of its extended blood circulation and high level of biocompatibility. In contrast to a supersulfide donor containing reduced polysulfide in HSA, the NACSn-conjugated HSAs exhibited stronger antioxidant activity than HSA and free NACSn without being uptaken by the cells in vitro. The supersulfide donor reduced the levels of blood urea nitrogen and serum creatinine significantly in a mouse model of rhabdomyolysis-induced AKI. Supersulfide donors significantly reduced the expression of oxidative stress markers in the kidney. These results indicate that the developed supersulfide donor has the therapeutic effect on rhabdomyolysis-induced AKI.

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Section: Discussionmentioning

confidence: 99%

Acute Kidney Injury Caused by Rhabdomyolysis Is Ameliorated by Serum Albumin-Based Supersulfide Donors through Antioxidative Pathways

Ikeda-Imafuku,

Fukuta,

Tuan Giam Chuang

et al. 2024

Pharmaceuticals

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“…Moreover, Froscio et al [ 41 ] reported that CYN uptake in Vero cells was slow but sufficient to induce cytotoxicity. More recently, Moraes et al [ 42 ] observed that CYN induced necrosis in all concentrations assayed (up to 1 µg/mL) in LLC-PK1 kidney tubular cells from pigs. This work reported for the first time in HEK293 cells at the molecular level that non-cytotoxic concentrations of CYN can modify the regulation of different genes.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Toxicity Evaluation of Cyanotoxins Cylindrospermopsin and Microcystin-LR on Human Kidney HEK293 Cells

Díez-Quijada

Puerto

Gutiérrez-Praena

et al. 2022

Toxins

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Cyanotoxins are secondary metabolites produced by different types of cyanobacteria. Among them, Cylindrospermopsin (CYN) and Microcystins (MCs) stand out due to their wide geographical distribution and toxicity in various organs, including the kidney, which is involved in their distribution and elimination. However, the renal toxicity caused by CYN and MCs has hardly been studied. The aim of this work was to assess the cytotoxicity effects caused by CYN and MC-LR in the renal cell line HEK293, and for the first time, the influence of CYN on the gene expression of selected genes in these cells by quantitative real-time PCR (qRT-PCR). CYN caused an upregulation in the gene expression after exposure to the highest concentration (5 µg/mL) and the longest time of exposure (24 h). Moreover, shotgun proteomic analysis was used to assess the molecular responses of HEK293 cells after exposure to the individuals and combinations of CYN + MC-LR. The simultaneous exposure to both cyanotoxins caused a greater number of alterations in protein expression compared to single toxins, causing changes in the cellular, lipid and protein metabolism and in protein synthesis and transport. Further studies are needed to complete the toxicity molecular mechanisms of both CYN and MC-LR at the renal level.

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