Altertoxin I
(Synonyms: 交链孢毒素I,Dihydroalterperylenol) 目录号 : GC42772A natural mycotoxin
Cas No.:56258-32-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: ≥95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Altertoxin I (Dihydroalterperylenol) is a quinone-type mycotoxin produced by Alternaria alternata fungi, which is mutagenic and cytotoxic, and can weakly disrupts metabolic communication[1].
References:
[1]. Jarolim K, et al. Activation of the Nrf2-ARE pathway by the Alternaria alternata mycotoxins altertoxin I and II. Arch Toxicol. 2017 Jan;91(1):203-216.
[2]. Boutin BK, et al. Effects of purified altertoxins I, II, and III in the metabolic communication V79 system. J Toxicol Environ Health. 1989;26(1):75-81.
[3]. Stack ME, et al. Mutagenicity of the Alternaria metabolites altertoxins I, II, and III. Appl Environ Microbiol. 1986 Oct;52(4):718-22.
| Cas No. | 56258-32-3 | SDF | |
| 别名 | 交链孢毒素I,Dihydroalterperylenol | ||
| 化学名 | (1S,12aR,12bS)-1,2,11,12,12a,12b-hexahydro-1,4,9,12a-tetrahydroxy-3,10-perylenedione | ||
| Canonical SMILES | O=C(CC[C@@]1(O)[C@@]([C@@H](O)C2)([H])C3=C4C=CC(O)=C3C2=O)C5=C1C4=CC=C5O | ||
| 分子式 | C20H16O6 | 分子量 | 352.3 |
| 溶解度 | 10mg/mL in dichloromethane | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8385 mL | 14.1924 mL | 28.3849 mL |
| 5 mM | 0.5677 mL | 2.8385 mL | 5.677 mL |
| 10 mM | 0.2838 mL | 1.4192 mL | 2.8385 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
General toxicity and genotoxicity of Altertoxin I: A novel 28-day multiendpoint assessment in male Sprague-Dawley rats
J Appl Toxicol 2022 Aug;42(8):1310-1322.PMID:35128692DOI:10.1002/jat.4297.
The mycotoxin Altertoxin I (ATX-I) is one of secondary metabolites produced by Alternaria fungi and is frequently detected as food and feed contaminants. Little is known about the genotoxicity of the ATX-I. In order to evaluate potential genotoxicity and general toxicity of ATX-I, the novel 28-day multiendpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity platform was applied. Male Sprague-Dawley (SD) rats were randomized to five groups (six rats per group), that is, a positive control group (N-ethyl-N-nitrosourea [ENU], 40 mg/kg.bw/d), two solvent control groups (PBS and corn oil), and two ATX-I-treated groups (low-dose group [1.10 μg/kg.bw/d] and high-dose group [5.51 μg/kg.bw/d]). Treatments were administered by oral gavage to male SD rats for 28 consecutive days. Histopathological damages in the liver, kidney, and spleen were observed, but without significant changes in hematological and serum biochemical parameters. Genotoxic endpoints indicated that ATX-I could cause DNA damage. To summarize, in a relatively low-dose range, ATX-I may not have direct genotoxicity in vivo but could induce liver, kidney, and spleen damage.
Altertoxin II, a Highly Effective and Specific Compound against Ewing Sarcoma
Cancers (Basel) 2021 Dec 7;13(24):6176.PMID:34944795DOI:10.3390/cancers13246176.
A screening program designed to identify natural products with selective cytotoxic effects against cell lines representing different types of pediatric solid tumors led to the identification of altertoxin II as a highly potent and selective cytotoxin against Ewing sarcoma cell lines. Altertoxin II, but not the related compounds Altertoxin I and alteichin, was highly effective against every Ewing sarcoma cell line tested, with an average 25-fold selectivity for these cells as compared to cells representing other pediatric and adult cancers. Mechanism of action studies revealed that altertoxin II causes DNA double-strand breaks, a rapid DNA damage response, and cell cycle accumulation in the S phase. Our studies also demonstrate that the potent effects of altertoxin II are partially dependent on the progression through the cell cycle, because the G1 arrest initiated by a CDK4/6 inhibitor decreased antiproliferative potency more than 10 times. Importantly, the cell-type-selective DNA-damaging effects of altertoxin II in Ewing sarcoma cells occur independently of its ability to bind directly to DNA. Ultimately, we found that altertoxin II has a dose-dependent in vivo antitumor efficacy against a Ewing sarcoma xenograft, suggesting that it has potential as a therapeutic drug lead and will be useful to identify novel targets for Ewing-sarcoma-specific therapies.
Activation of the Nrf2-ARE pathway by the Alternaria alternata mycotoxins Altertoxin I and II
Arch Toxicol 2017 Jan;91(1):203-216.PMID:27178040DOI:10.1007/s00204-016-1726-7.
The mycotoxins Altertoxin I and II (ATX I and II) are secondary metabolites produced by Alternaria alternata fungi and may occur as food and feed contaminants, especially after long storage periods. Although the toxic potential of altertoxins has been previously investigated, little is known about the pathways that play a role in their intracellular metabolism. In order to identify potential targets of ATX I and ATX II, the two toxins were tested for interaction with the nuclear factor erythroid-derived 2-like 2/antioxidant response element (Nrf2/ARE) pathway in mammalian cells. This pathway can be activated by various stressors resulting in the expression of enzymes important for metabolism and detoxification. In the present study, only ATX II triggered a concentration-dependent increase in Nrf2-ARE-dependent luciferase expression. Consistently, confocal microscopy revealed an ATX II-induced increase in Nrf2 signal in HT29 intestinal cells. In agreement with these data, ATX II induced the transcription of γ-glutamate cysteine ligase, the key enzyme in catalyzing GSH synthesis of the cells and which is regulated by Nrf2. Further investigations demonstrated that ATX II induced a concentration-dependent depletion of the cellular GSH levels after short incubation time (3 h) and an increase after longer incubation time (24 h). In conclusion, it was demonstrated that ATX II can interact at several levels of the Nrf2-ARE pathway in mammalian cells and that ATX I does not share the same mechanism of action.
The Fate of Altertoxin II During Tomato Processing Steps at a Laboratory Scale
Front Nutr 2019 Jun 13;6:92.PMID:31263702DOI:10.3389/fnut.2019.00092.
Among various agricultural crops, tomatoes are particularly prone to Alternaria infections, which are frequently resulting in economic losses and mycotoxin contamination. To investigate potential health concerns implied for consumers, we simulated the storage and food processing steps of intact and blended tomatoes after addition of the highly genotoxic secondary metabolite altertoxin II. We observed a significant decrease in altertoxin II concentrations in samples stored at room temperature and particularly those undergoing thermal treatment by employing a validated LC-MS/MS method. When kept at room temperature, 87-90% of ATX-II was recovered after 1.5 h in raw tomato purees and purees heated before ATX-II addition, and 47-49% were recovered after 24 h. In intact tomato fruits the recovery was 23% after 1.5 h and <1% after 24 h. In heated purees (100°C for 30 min after ATX-II addition), also only minor concentrations accounting for 2-4% were determined. Moreover, the reduction of the compound's epoxide group to the alcohol, i.e., the formation of Altertoxin I was demonstrated in intact tomato fruits (7-12%), suggesting enzymatic biotransformation of the xenobiotic by the plant's metabolism.
Effects of purified altertoxins I, II, and III in the metabolic communication V79 system
J Toxicol Environ Health 1989;26(1):75-81.PMID:2913335DOI:10.1080/15287398909531234.
Purified Alternaria alternata altertoxins I, II, and III were evaluated for comparative cytotoxicity and ability to inhibit gap junction communication in the Chinese hamster lung metabolic cooperation assay. The noncytotoxic test range for each altertoxin was determined for the metabolic communication assays: Altertoxin I, 1, 2, 3, 4, 5 micrograms/ml; altertoxin II, 0.02, 0.008, 0.006, 0.004, 0.002, 0.0008 micrograms/ml; and altertoxin III, 0.2, 0.1, 0.08, 0.06, 0.04 micrograms/ml. Altertoxin II was the most cytoxic in the V79 system, followed by altertoxins III and I. The last cytotoxic of the three, Altertoxin I, weakly disrupted metabolic communication at two concentrations (4 and 5 micrograms/ml). Altertoxins III and II did not significantly inhibit gap junction communication more than the weak tumor promoter 4-O-methyl ether tetradecanoylphorbol 13-acetate.