We were testing for the protective properties of ellagic acid against cancer by first treating the mice with ellagic acid for a period of 1 week then injecting them with benzo[a]pyrene. The ellagic acid used was in powder form which was dissolved in DMSO and injected using the intraperitoneal route. However, contrary to our research material, ellagic acid caused almost immediate diarrhea and caused many of the mice to die. Necropsy was performed after preservation in formalin and it showed a precipitation of yellow powder which we believe to be the original ellagic acid powder on the intestines near the injection site. Also, the intestines were agglutinated and the liver showed change as well with some of the lobes glued together as if they were one. Subsequent research has come up with nothing as all other articles show that ellagic acid is anti-cancer and anti-diarrheal. Could our result be because the ellagic acid used was not pure enough or not in hydrate form? After some searching I was able to find some evidence that ellagic acid in its synthesized form can have health risks unlike the whole ellagitannin complex that exists in pomegranate and some berries. However, the source is a site that sells the product so I'm not sure if I can trust this information...
This is the first time working with this type of material and any thoughts on this subject is greatly appreciated!
http://www.sigmaaldrich.com/catalog/product/sigma/e2250?lang=ko®ion=KR
https://www.vitapurity.com/e_acid.html
Hello, may be you can first check the dosage commonly used in previous reports, such as this: http://www.mdpi.com/1420-3049/19/11/18923
The paper used 50mg/kg.
It sounds like the animals died of multi-organ failure.
Almost any drugs, at extreme doses can have toxic or even lethal effects.
Another approach is to assess the toxicity and dose range in cancer cell lines first. Different cancer types (and their cell line variants) will have differential susceptibility.
So you need to decide what cancer types you want to focus on first.
Drug solubility is an important factor.
You can also check out this paper, which used an in vitro assay of HUVEC (human umbilical vascular endothelial cells). The purpose was likely to show anti-angiogenic effects. You can check on that.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409373/
From practical experience, I was told by a friend at Hopkins that even some antioxidants (like NAC, N-acetylcysteine) can kill cancer cells in vitro. There is this concept called reductive stress, which screws up the cellular redox environment.
You can gain a lot of inform from cell imaging by treating cells with a range of different doses, and see how and when the cells die.
I would recommend you move from cell based assays (get to know the doses, and cell behavior well), then to in vivo. It's easier and less costly.
Lastly, see this review (diagram). Polyphenols have been described to stimulate NO release (via eNOS; endothelial nitric oxide synthase). NO is a regulator of bowel movement. You may get some idea why high doses stimulate diarrhea instead.
http://www.nature.com/nrd/journal/v14/n9/fig_tab/nrd4623_F6.html
Good luck.
Dear Do Hee,
You might want to try another commercial source of ellagic acid.
Ellagic acid, derived from fruit ellagitannins, possesses antioxidant and antiproliferative effects, and is known as an antimutagenic and anticarcinogenic agent in various animal tumor models. Ellagic acid is a fused four-ring compound with four phenolic hydroxyl groups. It has been extensively studied in rodents for its tumor promotion inhibitory potential. Ellagic acid, administered through the diet has been known to be more bioavailable than when it is administered by i.p.route or as a subcutaneous implant or as topical application. It has been generally used at a concentration of 4 g/kg diet in rodent anticarcinogenicity studies. Please see below for safety information (NTP).
http://carcin.oxfordjournals.org/content/4/12/1651.abstract
Ellagic acid produced a severe toxicity by i.p. route, only after four injections of 100 mg/kg, in oil suspension in A/J mice. On the other hand, oral administration in the diet (a daily dose of 100 mg/kg during 15 days) did not elicit any toxicity.
http://ntp.niehs.nih.gov/testing/status/agents/ts-476664.html#Toxicity-Effects-HSDB-
http://tools.niehs.nih.gov/cebs3/ntpviews/index.cfm?action=testarticle.toxicity&cas_number=476-66-4
https://pubchem.ncbi.nlm.nih.gov/compound/ellagic_acid#section=Absorption-Distribution-and-Excretion
https://www.caymanchem.com/msdss/10569m.pdf
All the best...
The LD50 of DMSO in mice is 6.2mL/Kg. If a mouse is 20-30g and you inject any drug in DMSO at 0.1mL/10g body weight (0.2-0.3mL), it exceeds a lethal dose. http://hrcak.srce.hr/file/109943
Ellagic acid also has poor water solubility and is a know coagulant.
https://www.ncbi.nlm.nih.gov/pubmed/5902867
Specifically, ellagic acid activates Hageman factor (factor VII).
https://www.ncbi.nlm.nih.gov/pubmed/5645860
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