scholarly journals 5-aminolevulinic acid-induced accumulation of protoporphyrin IX in rat brain tissue

2021 ◽  
Vol 67 (6) ◽  
pp. 849-854
Author(s):  
Arina Kokorina ◽  
Artem Rafaelyan ◽  
Ksenia Chemodakova ◽  
Natalia Pak ◽  
Viktor Aleksandrov ◽  
...  

The aim of the study was to compare the level of accumulation of protoporphyrin IX (ППIX) in the brain of rats in normal conditions and in experimental C6 glioma. Materials and methods. In an experiment on 15 rats, one group of animals (n=5) was intracranially implanted with rat glioma of the C6 line. 14 days after tumor implantation, the animals were injected into the lateral vein of the tail with a photosensitizer — a preparation of 5-aminolevulinic acid (5-ALA) Alasens at a dose of 100 mg / kg. Another group consisted of 5 intact rats, which were also injected with Alasens. The rats were euthanized 4–5 hours after the injection of the photosensitizer, and fluorescent metabolic navigation was performed with illumination of the brain with light with wavelengths of 417 and 435 nm. For objectification, fluorescence biospectroscopy was performed. Similar manipulations were performed with animals of another group (n=5) — intact rats that did not receive Alasens. Results. In contrast to humans, in rats, the 5-ALA metabolite — PPIX accumulates in healthy brain tissue, while the fluorescence intensity does not differ from that visualized in the tumor area. It was also noted that the light of the blue spectrum promotes weak fluorescence of the white matter of the rat brain in the absence of exogenous 5-ALA, which can potentially be explained by the activation of endogenous PPIX or other fluorophores. Conclusion. After the administration of Alasens (5-ALA preparation), the accumulation of PPIX by the rat brain tissue occurs not only by malignant cells, but also by normal brain tissue without signs of malignancy or other pathological changes. A more thorough study of this phenomenon is required, since significant differences in the metabolism of 5-ALA in humans and laboratory animals will call into question the correctness of translation of experimental results into clinical practice.

2019 ◽  
Vol 15 (3) ◽  
pp. 251-257
Author(s):  
Bahareh Sadat Yousefsani ◽  
Seyed Ahmad Mohajeri ◽  
Mohammad Moshiri ◽  
Hossein Hosseinzadeh

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.


1972 ◽  
Vol 247 (8) ◽  
pp. 2322-2327
Author(s):  
Frederico A. Cumar ◽  
John F. Tallman ◽  
Roscoe O. Brady

1989 ◽  
Vol 9 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Michihiro Kirikae ◽  
Mirko Diksic ◽  
Y. Lucas Yamamoto

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-[18F]fluoro-2-deoxyglucose and L-[1-14C]-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis than glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: “kinetic” (quantitation done using an operational equation and the average brain rate coefficients) and “washed slices” (unbound labeled valine removed by washing brain slices in 10% thrichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using [11C]-valine with positron emission tomography.


2002 ◽  
Vol 323 (3) ◽  
pp. 207-210 ◽  
Author(s):  
Noriko Mochizuki-Oda ◽  
Yosky Kataoka ◽  
Yilong Cui ◽  
Hisao Yamada ◽  
Manabu Heya ◽  
...  

1993 ◽  
Vol 60 (5) ◽  
pp. 1639-1649 ◽  
Author(s):  
H.-P. Lipp ◽  
D. P. Wolfer ◽  
W. X. Qin ◽  
C. B. Klee ◽  
C. W. Heizmann

2021 ◽  
Vol 77 (11) ◽  
Author(s):  
Rabia Tasdemir ◽  
Tuncay Çolak ◽  
Belgin Bamaç ◽  
Süreyya Ceylan ◽  
Selenay Furat Rençber

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi174-vi174
Author(s):  
Luana Schaab ◽  
Yann Ferry ◽  
Mehmet Ozdas ◽  
Bettina Kritzer ◽  
Sulayman Mourabit ◽  
...  

Abstract Diffuse midline glioma (DMG) is a devastating and incurable childhood brain cancer. With a median survival of only 9 to 11 months, over 90% of children affected by DMG die within two years of diagnosis. Despite decades of research and a growing understanding of the biology of these tumors, there have been no advancements in therapies for DMGs. Tumor heterogeneity and diffuse infiltration in inoperable brain regions make these tumors uniquely difficult to manage both surgically and pharmacologically. Therefore, there is an urgent need for the exploration of novel treatment regimens. Focused Ultrasound (FUS) is an emerging technology with significant clinical potentials. Sonodynamic therapy (SDT) is an up-and-coming treatment strategy aiming to non-invasively eliminate tumor cells by acting through compounds known as sonosensitizers, which render tumor cells sensitive to ultrasound energy. Recently, 5-Aminolevulinic acid (5-ALA), an FDA-approved molecule, has been proposed as a sono-sensitizing agent. 5-ALA mediated SDT prolonged survival in C6 rat glioma models by selective elimination of tumor cells upon sonication. Mechanistically, it is thought that 5-ALA uptake and metabolic conversion into Protoporphyrin IX (PpIX) occurs preferentially in tumor cells due to differential activity of enzymes involved in heme metabolism. Here, we investigated SDT in DMG cells treated with 5-ALA. PpIX fluorescence increased linearly up to 24 h upon 5-ALA treatment and accumulated significantly more (1.6-fold, p < 0.01) when compared to C6 cells. Consequently, FUS sonication of 5-ALA treated DMG cells at 250 kHz significantly (p < 0.05) decreased DMG cell viability compared to treatment with 5-ALA or FUS alone. Here, we show the first 5-ALA mediated sonodynamic effect in DMG cells, leading to enhanced cell death. Our findings provide a rationale for considering clinical investigation of 5-ALA mediated sonodynamic therapy in DMG.


2011 ◽  
Vol 3 (8) ◽  
pp. 1729 ◽  
Author(s):  
Alice M. Delvolve ◽  
Benoit Colsch ◽  
Amina S. Woods

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