5-Aminolevulinic Acid (5-ALA): Analysis of Preclinical and Safety Literature

Problem: 5-ALA has been used for many years at relatively high dose amounts in single doses for photodynamic therapy and immunofluorescence of tumors. An analysis of compiled data relating to safety and any side-effects about the use of 5-ALA at low doses has not yet been published. Purpose: This report analyzes data about the safety of the use of 5-Aminolevulinic Acid (5-ALA) in low doses as a supplement over an extended period of time. Methods: This investigation is a systematic analysis of the current literature ((Medline, and SBI) and snowballing techniques) related to the safety and efficacy of 5-ALA in animals and humans. Clinical trials in progress using 5-ALA were also analyzed. Constant comparative analyses were used to synthesize the findings. Results: The safety of low-dose 5-ALA as a supplement has been demonstrated by animal and human studies. The results suggest that none of the investigations document the presence of symptoms or abnormal laboratory results of clinical significance. The minor laboratory changes documented were judged not clinically significant.

The Role of 5-Aminolevulinic Acid (5-ALA) and Sleep

Objective: To determine if there is a relationship between the administration of the dietary supplement containing 5-Aminolevulinic Acid (5-ALA) and sleep. Methods: A double-blind, randomized parallel-group study was conducted. It was a 4-month study of 40 participants between the ages of 40 and 70. Males and females were recruited equally. There were 20 in each group who had existing sleep disorders. The tool used to measure participant sleep improvement included the Pittsburgh Insomnia Rating Scale-20 Question (PIRS-20). Improved sleep is reflected when the total PIRS-20 score is lower. Results: Improvement in sleep in the group taking 50 mg 5-ALA, compared to controls, was significant. The mean change, from baseline through week 6, was -5.67 units less on the sleep scale than the control group with a p value of 0.001. The mean change from week 6 to week 10 when the participant was no longer taking the supplement was 4.55 units higher than the control group with a p value of 0.062, which is of borderline significance. Conclusions: There is a relationship between the administration of dietary supplements containing 5-ALA and sleep. The results of this study suggest that 5-ALA is associated with improved sleep. The mechanism for sleep improvement needs to be explored. Further research is warranted.

Effects of 5-Aminolevulinic Acid (ALA) on Zinnia hybrida Growth and Phytoremediation Effects in Oil-Contaminated Soil

In this study, we compared plant height, weight, soil TPH concentration, and soil DHA level after 18 weeks of Zennia hybrida cultivation with four different concentrations of 5-Aminolevulinic acid (ALA)-based liquid fertilizer: 1500-fold, 5000-fold, and 8000-fold dilutions, along with a non-treatment control of diluted ALA. The plants of ALA-treated were significantly taller than the non-treatment control. The plants of ALA-treated plants were higher in shoot fresh weight, shoot dry weight, and root dry weight than the non-treatment control. The plot of ALA-based liquid fertilizer with the 5000-fold dilution was significantly highest in shoot fresh weight, shoot dry weight, and root dry weight. ALA-treated plants were lower in the soil Total Petroleum Hydrocarbon (TPH) concentration than the non-treatment control. The plot of ALA-based liquid fertilizer with the 5000-fold was significantly lowest in the TPH concentration. In addition, ALA-treated plants were higher in the soil dehydrogenase activity (DHA) than the non-treatment control. The plot of ALA-based liquid fertilizer with the 5000-fold was significantly highest in the TPH concentration. This study indicated that ALA-applied zinnia-grown oil-contaminated soil is more effective than not. The remediation in oil-contaminated soil with ALA-based liquid fertilizer is more effective than the non-treatment control;furthermore, ALA application with 5000-fold dilution was most suitable in oil-contaminated soil among other plots.

Study on Insecticidal Activities and Effect on Three Kinds of Enzymes by 5-Aminolevulinic Acid on Oxya chinensis

Insecticidal activities and effects on three enzymic activities caused by 5-aminolevulinic acid （ALA） on Oxya chinensis were studied. Fourth-instar nymphs of O. chinensis were treated with different doses ofALA （A1,250 mM; A2, 450 mM; A3,750 mM; A4, 1 000 mM）. Mortality and the activities of acetylcholinesterase （ACHE）, glutathione S-transferase （GSTs）, and glutathione peroxidase （GPx） were determinated. The mortality of O. chinensis rose with an increasing dose of ALA. The mortality of high-dose treatments A3 and A4 reached 66.19 and 80.21%, respectively. The value of LD50 was 3.61 （3.29-3.93） mg·g^-1 body weight （95% confidence interval）. Biochemical studies showed that the activities of AChE and GPx in the A4 treatment declined by 51.53 and 42.82% in the female, and 42.65 and 43.85% in the male compared to the control, respectively, and the degree of decline reached a significant level at P 〈 0.05. Meanwhile, the GSTs activities of O. chinensis enhanced with increasing dose of ALA. The GSTs activities of female and male O. chinensis in the A4 treatment remarkably increased by 171.05 and 97.42% compared to the control （P〈 0.05）. ALA had an obviously toxic effect on O. chinensis. Moreover, ALA caused the photoinactivation of AChE and GPx, which induced nerve transmission blocking and the capability to defend oxidation damage declining. Meanwhile, a high dose of ALA could activate GSTs, which caused a feedback inhibition of the insect to the phototoxic substance.

Biological formation of 5-aminolevulinic acid by photosynthetic bacteria

In this study, 7 stains of Rhodopseudomonas sp. were selected from 36 photosynthetic bacteria stains storied in our laboratory. Rhodopseudomonas sp. strain 99 28 has the highest 5 aminolevulinic acid(ALA) production ability in these 7 strains. Rhodopseudomonas sp. 99 28 strain was mutated using ultraviolet radiation and a mutant strain L 1, which ALA production is higher than wild strain 99 28 about one times, was obtained. The elements affecting ALA formation of strain 99 28 and L 1 were studied. Under the optimal condition(pH 7 5, supplement of ALA dehydratase(ALAD) inhibitor, levulinic acid(LA) and precursors of ALA synthesis, glycine and succinat, 3000 lx of light density), ALA formation of mutant L 1 was up to 22 15 mg/L. Strain L 1 was used to treat wastewater to remove COD Cr and produce ALA. ALA production was 2 819 mg/L, 1 531 mg/L, 2 166 mg/L, and 2 424 mg/L in monosodium glutamate wastewater(MGW), succotash wastewater(SW), brewage wastewater(BW), and citric acid wastewater(CAW) respectively. More than 90% of COD Cr was removed in four kinds of wastewater. When LA, glycin and succinate were supplied, ALA production was dramatically increased, however, COD Cr could hardly be removed.

Clinical applications of 5-aminolevulinic acid-mediated fluorescence for gastric cancer

5-aminolevulinic acid(ALA) is a naturally occurring amino acid that is a protoporphyrin IX(Pp IX) precursor and a next-generation photosensitive substance. After exogenous administration of ALA, Pp IX specifically accumulates in cancer cells owing to the impaired metabolism of ALA to Pp IX in mitochondria, which results in a red fluorescence following irradiation with blue light and the formation of singlet oxygen. Fluorescence navigation by photodynamic diagnosis(PDD) using ALA provides good visualization and detection of gastric cancer lesions and is a potentially valuable diagnostic tool for gastric cancer for evaluating both the surgical resection margins and extension of the lesion. Furthermore, PDD using ALA might be used to detect peritoneal metastases during preoperative staging laparoscopy, where it could provide useful information for the selection of a therapeutic approach. Another promising application for this modality is in the evaluation of lymph node metastases. Photodynamic therapy(PDT) using ALA to cause selective damage based on the accumulation of a photosensitizer in malignant tissue is expected to be a non-invasive endoscopic treatment for superficial early gastric cancer. ALA has the potential to be used not only as a diagnostic agent but also as a therapeutic drug, resulting in a new strategy for cancer diagnosis and therapy. Here, we review the current use of PDD and PDT in gastric cancer and evaluate its future potential beyond conventional modalities combined with a light energy upconverter, a light-emitting diode and nearinfrared rays as light sources.

Effects of Exogenous 5-Aminolevulinic Acid and 24-Epibrassinolide on Cd Accumulation in Rice from Cd-Contaminated Soil

High grain-Cd-accumulating rice variety Yongyou 9 was planted in Cd-contaminated farmland in Taizhou City, Zhejiang Province, China to study the effects of 5-aminolevulinic acid(ALA) and24-epibrassinolide(EBR) on Cd accumulation in brown rice. Results showed that the exogenous ALA and EBR had no significant effects on agronomic traits, soil pH and total Cd content in soil, but had some effects on the available Cd content in soil, and significantly influenced the Cd accumulation in the different parts of rice. Results also showed that 100 mg/L exogenous ALA significantly reduced the Cd accumulation in brown rice to blow the food safety standard(0.2 mg/kg), and also significantly reduced the Cd contents in the roots and culm of rice. However, 200 mg/L exogenous ALA treatment increased the Cd content in brown rice remarkably. In addition, 0.15 mg/L EBR treatment increased Cd accumulation in roots, culm, leaves and brown rice notably, whereas 0.30 mg/L exogenous EBR treatment reduced the Cd accumulation in brown rice properly, but it was not significant. Therefore,proper concentration of ALA can effectively reduce the Cd accumulation in brown rice, which can be used as an effective technical method for the safe production of rice in Cd polluted farmland.

Recent advances in photodynamic diagnosis of gastriccancer using 5-aminolevulinic acid

Photodynamic diagnosis based on 5-aminolevulinic acidinduced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative realtime fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma.

Improved 5-Aminolevulinic Acid Production with Recombinant Escherichia coli by a Short-term Dissolved Oxygen Shock in Fed-batch Fermentation

5-Aminolevulinic acid(ALA) is a common precursor for tetrapyrrole compounds in all kinds of organisms and has wide applications in agriculture and medicines. In this study, a new strategy, i.e. short-term dissolved oxygen(DO) shock during aerobic fermentation, was introduced to produce 5-aminolevulinic acid with a recombinant E. coli. Effects of duration time of DO shock operation on plasmid concentration, intracellular ALA synthase(ALAS) activity and ALA production were investigated in Erlenmeyer shake flasks. The results indicated that both ALAS activity and ALA yield were enhanced in an anaerobic operation of 45 min in the early exponential phase during fermentation, while they decreased when the anaerobic operation time was further increased to 60 min. The DO shock protocol was confirmed with the fed-batch fermentation in a 15 L fermenter and the ALA production achieved 9.4 g·L 1(72 mmol·L 1), which is the highest yield in the fermentation broth reported up to now.

A Photosensitivity Insecticide, 5-Aminolevulinic Acid, Exerts EffectiveToxicity to Oxya chinensis (Orthoptera: Acridoidea)

5-Aminolevulinic acid （ALA）, a major photosensitivity insecticide, has attracted increasing attention as a new type of highly efficient, environmental friendly pesticide to be used to control the pest. To examine whether or not ALA acts effectively to grasshopper, Oxya chinensis and elucidate the detoxification mechanism of ALA, the susceptibility to ALA was assessed in O. chinensis and two major metabolic detoxification enzymes including glutathione S-transferases （GSTs） and general esterases （ESTs）-specific activities were compared in different development stages and different body sections of O. chinensis treated by ALA and the control. The results showed that the ALA exhibited obvious toxicity to the grasshopper in different development stages. In the low-dose treatment （0.0597 mmol L-1）, the mortalities of O. chinensis reached a significant level （55.5% in the 1st instar nymphs, 61.4% in the 2nd instar nymphs, 71.4% in the 3rd instar nymphs, and 64.4% in the 4th instar nymphs. But, there was no dose-dependent toxic effect. Thereby, we proposed that ALA has the potential for acting as photosensitivity insecticide for controlling O. chinensis. GSTs activity assays using CDNB and DCNB as substrates indicated that the thorax and abdomen of the different instar nymphs treated by ALA showed 1.52-5.56 fold significantly increased GSTs activities compared with the control. However, for the ESTs-specific activity assay, there was no significant difference between O. chinensis treated by ALA and the control within different instar nymphs, when a-NA, a-NB and b-NA were used as substrates. Therefore, GSTs-mediated metabolic detoxification as evidenced by significantly increased GSTs activities might contribute to protect against oxidative damage and oxidative stress by ALA in O. chinensis.

Development of a Photodynamic Diagnosis Method for Oral Squamous Cell Carcinoma Using 5-Aminolevulinic Acid and a Luminescence Plate Reader

Purpose: To establish a simple and accurate photodynamic diagnosis (PDD) method for oral squamous cell carcinoma (OSCC). Methods: OSCC cell lines HSC-2, HSC-3, HSC-4, and Sa3, and normal human oral keratinocytes (HOK) were used. First, we examined the amount of cells needed to detect differences in fluorescence intensities for PDD. OSCC cell lines were adjusted to concentrations of 1 × 104 (104), 1 × 105 (105), and 1 × 106 (106) cells/ml. The experimental groups comprised a group with 5-aminolevulinic acid (5-ALA (+)), and a group without 5-ALA (5-ALA (-)). For each OSCC cell line, 100 μl of each concentration of cells of the 5-ALA groups was seeded onto fluorescence plates, and fluorescence intensity was measured at 60-min intervals for 240 min. Results are expressed as the ratio of fluorescence intensity in 5-ALA (+) to 5-ALA (-). As cells at the concentration of 106 cells/ml provided the clearest results, fluorescence intensities of all cell lines were measured using this concentration at 20-min intervals for 700 min using the same methods. Results: The 5-ALA (+) to (-) ratio increased in a cell concentration-dependent manner at 240 min;the ratio was highest with 106 cells/ml and lowest with 104 cells/ml. With 106 cells/ml in the 5-ALA (+) group, fluorescence intensity increased in a metabolic time-dependent manner;the increase was highest in HSC-2 cells, followed by HSC-4 cells, HSC-3 cells, Sa3 cells, and HOK. Fluorescence intensity was significantly enhanced after 40 min in HSC-2, HSC-3, and HSC-4 cells, after 60 min in Sa3 cells, and after 100 min in HOK compared to the 5-ALA (-) group (P < 0.05). Moreover, fluorescence intensity was significantly increased in OSCC cell lines compared to HOK after 40 min. Conclusion: Early detection of OSCC is possible by screening only microplate reader measurements of fluorescence intensity for PDD.

OPTIMIZATIONS FOR 5-AMINOLEVULINIC ACID BASED PHOTODYNAMIC THERAPY IN PURGING LEUKEMIA CELL HL60

Objective To optimize experimental parameters for the photosensitization of 5-aminolevulinic acid (ALA) in promyelocytic leukemia cell HL60 and compare them with normal human peripheral blood mononuclear cell (PBMC). Methods ALA incubation time, wavelength applied to irradiate, concentration of ALA incubated, irradiation fluence may modulate the effect of 5-aminolevulinic acid based Photodynamic Therapy (ALA-PDT).The high-pressure mercury lamps of 400W served as light source, the interference filter of 410nm, 432nm, 545nm, 577nm were used to select the specific wavelength. Fluorescence microscope was used to detect the fluorescence intensity and location of protoporphyrin IX (PpIX) endogenously produced by ALA. MTT assay was used to measure the survival of cell. Flow cytometry with ANNEXIN V FITC kit (contains annexin V FITC, binding buffer and PI) was used to detect the mode of cell death. Results ① 1mmol/L ALA incubated 1×105/mL HL60 cell line for 4 hours, the maximum fluorescence of ALA induced PpIX was detected in cytomembrane. ② Irradiated with 410nm for 14.4J/cm2 can result in the minimum survivability of HL60 cell. ③ The main mode of HL60 cell death caused by ALA-PDT is necrosis. Conclusion ALA for 1mmol/L, 4 hours for dark incubation time, 410nm for irradiation wavelength, 14.4J/cm2 for irradiation fluence were the optimal parameters to selectively eliminate promyelocytic leukemia cell HL60 by ALA based PDT. The photosensitization of ALA based PDT caused the necrosis of HL60 cell, so it could be used for inactivation of certain leukemia cells.

COMPARISON OF AMINOLEVULINIC ACID AND ITS METHYL ESTER MEDIATED PHOTOCYTOTOXICITY ON HUMAN NASOPHARYNGEAL CARCINOMA CELLS

Nasopharyngeal carcinoma(NPC)is a prevalent cancer in some areas of southern Asia.To explore the potential of photodynamic therapy(PDT)for the treatment of NPC,a small molecule prodrug 5-aminolevulinic acid(ALA)and its methyl ester(MAL)mediated PDT was studied in vitro.The results showed that human NPC cells were sensitive to both ALA-and MAL-mediated PDT.However,ALA was more effective than MAL,possiblly due to a higher efficiency of ALA on producing endogenous protoporphyrin(PpIX)in NPC cells.Neither ALA nor MAL caused any significant genotoxicity.The ALA-based PDT might be a useful modality in the treatment ofNPC.

Photodynamic therapy with topical aminolevulinic acid

Photodynamic therapy(PDT) is a relatively new therapy in dermatology that uses the topical application of a porphyrin derivative to selectively destroy a cutaneous target. The action is implemented by the application of a specific light frequency. The ability of porphyrin to selectively target tumor tissue has been known since the 1960 s. In the late 1970 s, the underlying mechanism was defined, and Dougherty's discovery of the first chromophore led to the production and commercialization of Photofrin. Many other chromophores that can act as photosensitizers have been studied since then, with aminolevulinic acid currently the most commonly used chromophore in clinical practice. PDT is simple, minimally invasive and can be administered on an outpatient basis. The efficacy of PDT has been proven for actinic keratosis, Bowen's disease and basal cell carcinoma; another of its well-known applications is the treatment of photoaging. Indications for its use are continuously increasing, and promising results are reported for various skin diseases. In this paper we report the mechanism of action of PDT with aminolevulinic acid, the literature concerning the most common diseases treated with PDT and the subsequent level of evidence.

ALA协同PASP强化伴矿景天提取土壤重金属Cd的研究

[目的]探究5-氨基酮戊酸(ALA)协同螯合剂聚天冬氨酸(PASP)增强伴矿景天提取土壤Cd的最佳条件。[方法]通过盆栽试验,伴矿景天种植于Cd污染土壤(总Cd0.68 mg/kg)中,且在移栽45 d后开始浇灌不同添加浓度的PASP(3、6、12 g/kg,分别等分为3次使用,2~3次使用的间隔时间分别为15、30 d);ALA(25 mmol/L)于PASP处理后第3天灌施,按不同的施用次数(0、1、2、3)处理,间隔时间同PASP处理。分析伴矿景茎长、地上部生物量、Cd含量和Cd提取量,建立各指标之间的相关性并拟合生物量和Cd提取量与PASP施用量、ALA使用次数的预测模型。[结果]ALA协同中等剂量(6 g/kg)PASP连续3次的施用能显著提高伴矿景天茎长、地上部生物量、地上部分Cd含量和Cd提取量;线性回归显示PASP施用量和ALA施用次数是地上部分生物量和Cd提取量的关键影响因子;地上部分Cd提取量在PASP施用量为6 g/kg协同ALA 3次连续使用时达到最大,为1.09 g/盆,是CK提取量的2.79倍;地上部分生物量、茎长与ALA施用次数呈显著正相关,而与PASP施用量呈显著负相关。[结论]研究结果揭示了ALA协同PASP在强化伴矿景天提取土壤Cd具有重要意义,且需选择合适的配比和施用次数。

Preliminary study of photodynamic diagnosis using 5-aminolevulinic acid in gastric and colorectal tumors

AIM:To investigate the utility of photodynamic diagnosis(PDD) using 5-aminolevulinic acid(5-ALA) to detect gastric/colorectal tumors.METHODS:This prospective single-center study investigated inter-subject variability in patients with early-stage gastric/colorectal tumor indicated for endoscopic resection.Subjects were patients with gastric or colorectal tumors who had undergone endoscopic resection between November 2012 and November 2013.Selection criteria included age 20-80 years,either sex,and provision of informed consent.Patients were orally administered 20 mg/kg of 5-ALA enteric-coated capsules(SBI ALApromo Co.,Tokyo,Japan).Administration of5-ALA was followed by endoscopic resection of gastric or colorectal tumors,and the resected specimens were examined using a video autofluorescence processor and a fluorescence endoscope(SAFE-3000 and EB-1970 AK,respectively;Pentax,Tokyo,Japan).The primary endpoint was the presence of fluorescence in tumors.Endoscopic,macroscopic,and histopathologic findings of tumors were assessed.We also evaluated adverse events of the present procedure as a secondary endpoint and examined each patient for the presence of known adverse effects of 5-ALA,namely,hematocytopenia,liver dysfunction,hypotension,nausea,and photosensitivity.RESULTS:We enrolled 10 patients(7 men,3 women)(n = 13 lesions:10 gastric/3 colorectal tumors).Fluorescence was detected in 7/13(53.8%) lesions.No significant differences in sex(male:55.6%vs female:50.5%,P = 1.00),age(67.1 ± 1.9 years vs 65.0 ±2.0 years,P= 0.45),tumor color(reddish:60.0%vs discolored:33.3%,P = 0.56),tumor diameter(15.0± 2.1 mm vs 14.2 ± 2.3 mm,P= 0.80),macroscopic type(protruded:70.0%vs depressed 0%,P = 0.07),histologic type(differentiated type:58.3%vs 0%,P = 0.46),invasion depth(mucosal layer:55.6%vs submucosal layer:33.3%,P = 1.00),lymphatic invasion(present:33.3%vs absent:50.0%,P= 1.00),venous invasion(present:0%vs absent:54.5%,P= 1.00) or procedure time of endoscopic resection(36.3 ± 8.3 min vs 36.7 ± 9.0 min,P = 0.98) were observed between the patients with and without fluorescence.Fluorescence detection rate tended to be high for elevated lesions.Liver dysfunction developed in 4/10(40.0%) patients.The extent of the liver dysfunction was a slight increase in transaminases and total bilirubin levels,which spontaneously improved in the patients.None of the patients developed photosensitivity.CONCLUSION:Results of this preliminary study suggest the utility of PDD using 5-ALA for screening of gastric and colorectal cancers.

Photodynamic Therapy of Cancer Cells with Methanesulfonate Salts of 5-Aminolevulinic Acid and Its Derivatives

A series of 5-aminolevulinic acid and its alkylester methanesulfonates was exploited to photodynamic therapy（PDT） of human lymphocytic cells, U-937 in vitro. The PDT efficiency is influenced by the concentration and incubation time. Generally, for ALA and its alkylester methanesulfonates, the cell survival rate decreases and the accumulation ability of PplX increases with the concentration and incubation time. We found that the longer carbon chain methanesulfonates（C5-S, C6-S, C8-S） exhibit better PDT effect than ALA methanesulfonate. This possibly provides a promising route to the clinical application ofPplX-mediated PDT to cancer cell.

5-Aminolevulinic Acid Improves Water Content and Reduces Skin Wrinkling

5-Aminolevulinic acid (ALA) is a natural amino acid that is used as a raw material for the biosynthesis of red-blood-cell hemoglobin in humans and animals. ALA is the subject of research in a wide range of human health care fields, including skin care and medicine. This study investigated whether and to what extent cosmetics containing ALA (skin lotions and creams) improved facial-skin condition in women. As such, a double-blind controlled experiment was conducted among 45 women aged 47.0 ± 1.72 years. Participants were divided into two intervention groups, including those who used cosmetics containing ALA (C-ALA, n = 22) and those who used cosmetics without ALA (W-ALA, n = 23). Specifically, participants were instructed to use their assigned cosmetics twice per day (morning and evening) after washing their faces before each application. Inner skin condition and skin-water content were evaluated via VISIA-Evolution and Multi Display Devices at baseline and after four and eight weeks of use. The experiment lasted for a total of eight weeks. A baseline comparison at week four showed that skin moisture content increased significantly for the C-ALA group (p = 0.021). Further, wrinkling significantly decreased at week four among participants in the C-ALA group who were evaluated as having many wrinkles at baseline (p = 0.034). These findings suggest that cosmetics containing ALA have moisturizing effects and reduce wrinkling caused by dryness.

Low Frequency Ultrasonication Induced Antitumor Effect in 5-Aminolevulinic Acid Treated Malignant Glioma

We investigated the feasibility of sonodynamic therapy for glioma by low frequency ultrasoundwith5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX) in heme synthetic process. In vivo tumor model was made by inoculating human glioma cell line U87-MG subcutaneously in nude mice. The tumor was sonicated by 25-kHz ultrasound 4 hours following administration of 5-ALA. The tumor size decreased in 5-ALA administered (ALA(+)US(+)) mice, while increased in non-5-ALA administrated (ALA(-)US(+)) mice and non-sonicated mice (ALA(+)US(-)). The immunohistochemical analysis revealed an apoptotic change in tumor tissue of ALA(+)US(+) mice. The results showed the therapeutic effect of 25 kHz ultrasound for the glioma in 5-ALA administered tumor-bearing mice by inducing apoptotic change of tumor cells. This is a first report to elucidate the feasibility of therapeutic use of 25 kHz, relatively low frequency, ultrasound in sonodynamic therapy using 5-ALA as a sonosensitizer precursor. The utilization of this frequency will contribute to the development of sonodynamic therapy for gliomas and the spread of this technique in many hospitals that possess ultrasonic aspirators.

Review of literature: Role of 5-aminolevulinic acid and sleep

Objective: To determine if current peer-reviewed literature supports the existence of a relationship between the administration of dietary supplements containing 5-Aminolevulinic Acid (5-ALA) and sleep. Methods: Conceptual analysis of a systematically defined group of data is based on publications in referred journals. Constant comparative analyses were used to analyze the data. Detailed analyses were used to identify trends that led to qualifying relationships between the use of 5-ALA and heme. In addition, the relationship among heme, melatonin, and sleep were explored. Since there were no published data related to 5-ALA and sleep, an analysis of what is known about 5-ALA and heme was undertaken. Results: Currently, within the scope of this review, no literature available directly connecting 5-ALA and sleep was found. Research indicates that 5-ALA has an indirect relationship with intra-cellular energy production, which could result in a wide range of effects fromcellular to endocrine to neurologic to behavioral. In addition, there is evidence that 5-ALA may influence tryptophan and serotonin levels. Conclusion: While there are no studies on 5-ALA and sleep were found, current research suggests several potential mechanisms by which 5-ALA could influence sleep. The mechanisms suggest the potential for 5-ALA to assist in the adjustment of a person’s circadian cycle, endocrine function, or neurologic function in order to allow for better sleep in a natural way. In doing so, it may provide for a safer alternative to currently available sleep medication. Further research is needed to explore this possibility.