Mast Cell Disorders Forum - Statins have mast cell stabilising benifits

Josie

Ex Member

Statins have mast cell stabilising benifits
02/13/11 at 08:50:47

European Journal of Pharmacology
Volume 602, Issues 2-3, 14 January 2009, Pages 432-438

Hi All ,

I found this article titled . In it it demonsatrates 3 statins for cholesterol which have mast cell stabilising benifits .

Fluvastatin inhibits mast cell degranulation without changing the cytoplasmic Ca2+ level
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Masanori Fujimotoa, Tatsuya Okaa, Takahisa Murataa, Masatoshi HoriCorresponding Author Contact Information, a, E-mail The Corresponding Author and Hiroshi Ozakia

Abstract

We evaluated the pharmacological effect of statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) on mast cell degranulation in RBL-2H3 cells. A hydrophilic statin (pravastatin) did not inhibit degranulation induced by dinitrophenol-human serum albumin (DNP-HSA); in contrast, lipophilic statins (simvastatin, fluvastatin and atorvastatin) inhibited DNP-HSA-induced degranulation in that order.

The inhibitory effects were completely attenuated by simultaneous treatment with 100–1000 µM mevalonic acid for 4 h. We used fluvastatin to clarify the mechanism of the statin-mediated inhibitory action of mast cell degranulation.

Fluvastatin (3 µM) had no effect on Ca2+ release from the endoplasmic reticulum or Ca2+ influx in the DNP-HSA- or thapsigargin-stimulated cells.

Fluvastatin treatment also had no effect on the total granule content of the cell or sensitivity to DNP-HSA and IgE. Fluvastatin (3 µM, 24 h treatment) also failed to affect the morphology, proliferation, and viability of RBL-2H3 cells. Geranylgeranyl transferase inhibitor, GGTI-286 (20 µM), but not farnesyl transferase inhibitor, FPTIII (20 µM), inhibited the DNP-HSA-induced degranulation. The GGTI-286-induced inhibitory action was not associated with a decrease in the cytoplasmic Ca2+ level. In conclusion, fluvastatin at a lower concentration range inhibited DNP-HSA-induced degranulation without affecting the cytoplasmic Ca2+ response and also without changing the amount of granule content and proliferation of the mast cells. The statin-induced inhibitory action may be mediated by the suppression of geranylgeranyl transferase via the depletion of intracellular mevalonic acid.

I will look for work on Simvastsin as this is the top inhibitor and for those who can't tolerate corn in meds it is availble in liquid form in the UK.

Is this new information ? i will get the full article . Cheesy

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Josie

Ex Member

Re: Statins have mast cell stabilising benifits
Reply #1 - 02/13/11 at 08:55:18

Quote:

European Journal of Pharmacology
Volume 602, Issues 2-3, 14 January 2009, Pages 432-438
Masanori Fujimotoa, Tatsuya Okaa, Takahisa Murataa, Masatoshi HoriCorresponding

Hi All ,

I found this article titled . In it it demonsatrates 3 statins for cholesterol which have mast cell stabilising benifits .

Fluvastatin inhibits mast cell degranulation without changing the cytoplasmic Ca2+ level

Abstract

We evaluated the pharmacological effect of statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) on mast cell degranulation in RBL-2H3 cells. A hydrophilic statin (pravastatin) did not inhibit degranulation induced by dinitrophenol-human serum albumin (DNP-HSA); in contrast, lipophilic statins (simvastatin, fluvastatin and atorvastatin) inhibited DNP-HSA-induced degranulation in that order.

The inhibitory effects were completely attenuated by simultaneous treatment with 100–1000 µM mevalonic acid for 4 h. We used fluvastatin to clarify the mechanism of the statin-mediated inhibitory action of mast cell degranulation.

Fluvastatin (3 µM) had no effect on Ca2+ release from the endoplasmic reticulum or Ca2+ influx in the DNP-HSA- or thapsigargin-stimulated cells.

Fluvastatin treatment also had no effect on the total granule content of the cell or sensitivity to DNP-HSA and IgE. Fluvastatin (3 µM, 24 h treatment) also failed to affect the morphology, proliferation, and viability of RBL-2H3 cells. Geranylgeranyl transferase inhibitor, GGTI-286 (20 µM), but not farnesyl transferase inhibitor, FPTIII (20 µM), inhibited the DNP-HSA-induced degranulation. The GGTI-286-induced inhibitory action was not associated with a decrease in the cytoplasmic Ca2+ level. In conclusion, fluvastatin at a lower concentration range inhibited DNP-HSA-induced degranulation without affecting the cytoplasmic Ca2+ response and also without changing the amount of granule content and proliferation of the mast cells. The statin-induced inhibitory action may be mediated by the suppression of geranylgeranyl transferase via the depletion of intracellular mevalonic acid.

I will look for work on Simvastsin as this is the top inhibitor and for those who can't tolerate corn in meds it is availble in liquid form in the UK.

Is this new information ? i will get the full article . Cheesy

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TRama

Ex Member

Re: Statins have mast cell stabilising benifits
Reply #2 - 02/14/11 at 02:44:25

Dear Josie,

Statins have serious adverse effects and are known to interact with drugs that mastocytosis patients usually take. Ranitidine is one of those drugs!!

Also, that is an experimental study with cultured cells - scientific evidence is thus very low! LDL-cholesterol is known to induce MC activation. In my opinion (which according to the principles of evidence based medicine is not worth much), statins are probably good drugs for mastocytosis patients suffering from dislipidemia. For the remaining patients, I would not venture in taking them.

Tiago Rama, DMD

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Lisa

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Volta Redonda, RJ Brazil

Re: Statins have mast cell stabilising benifits
Reply #3 - 02/14/11 at 04:12:06

Tiago,

Thank you so very much for this statement of yours! I have been reading about the negative aspects of the statins and although I do not have any kind of lipid problems, I have questioned why my doctors put me on them. It was my angiologist who put me on the statins, but with the recent research I have questioned why I would need to be on them. My cardiologist doesn't seem to understand what my questions are and yet I still prefer not to be on them unless my lipids were to show a need for this.

So, thank you for this opinion of yours! One of the things my masto specialist has said to me recently is that I should not worry way too much about what my other doctors have to say with some medicines for they don't understand mast cells and their function and they 're not understanding my medications in respect to the masto and this is possibly causing some issues with me. We're finding that in my case my combination of H1 and H2 blockers may be causing a beta blocker affect and in some patients this apparently can happen. But all of this needs to still be investigated and so it's a complicated affair. Sometimes I wonder who I must listen to more, but my instincts tell me it's my masto specialist!

So, thank you for that opinion, it's a confirming voice!

Lisa

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Josie

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Re: Statins have mast cell stabilising benifits
Reply #4 - 02/14/11 at 10:27:37

Hi Lisa and T rama ,

I am aware of the notable stain side effects as I was a cardiology nurse . I am not aware of ranitidine interactions .

In relation to my illness I need all the information I can get

My cholesterol due to my diabetes is high . On my last reading it was greater than 10 . I didnt tolerate fenofibrate . I know they are going to want me to have a stain. So I thought I had found something useful . I realised it was a scientific study . But it backed up evidance as simvastsin as a mast cell stabiliser .

Reagrding interavtions

A check of the british national formulary drug interaction lisy for simvastsin shows nothing for ranitidine and simvastain ( searched from both sides ) There is nothing in the patient leaflet either .

Can you tell me the exact nature of the interaction known as without any clear interactions documented I will struggle to make a case against stains in my case

I hope sugar control will be my best route to cholesterol control .

I am interested that LDL cholesterol is a mast cell activator so my high cholesterol , which is a mainly triglycerides , but high on all levels , may be contributing to my current situation .

hugs
Jose

What now ???

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Lisa

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I am not a doctor.
Posts: 1499
Volta Redonda, RJ Brazil

Re: Statins have mast cell stabilising benifits
Reply #5 - 02/14/11 at 12:27:34

Hey Josie, as to the ranitidine interaction I read that ranitidine ends up interfering with many meds, Josie due to how it deals with the acidity in the stomach and I'll bet that this is what Tiago is talking about. Ranitidine isn't good to be taking with fungal medications either and that was news to my gyno when we were treating a candida infection.

As to the statins, what Dr. Tiago was talking about was that recent research has shown that statins are causing some serious side affects of their own and therefore they are not being seen as the all safe answer to cholesterol problems - so those of us who really don't have issues with our lipids, then the use of the statins isn't perhaps the best move to make. But each case is a case and so this is why this needs the involvement of our doctors to help us understand these issues. But if you DO have cholesterol problems then you should be on them. And, here's another reason why - since you get hipertensive in your crises, that hipertension creates issues with the blood vessels in your brain and by taking statins you can avoid some potential issues by using the statins.

So, Josie, I recommend that you speak with this doctor that you're seeing in March about these issues. I think what's important here is that you can't take every bit of research that you come across and get stirred up about it. I had one person tell me whose job was as a writer of research articles say that you can't take it all at face value. My own doctors, in working with my case don't take it all at face value either. They feel that some things may apply but really, what the researchers know is that until other studies are performed one researcher's findings don't hold water! They are considered findings, but don't have a whole lot of value until other researchers take that finding and expand upon it and either confirm that work or toss it out the window!

So, take this article you found and consider it, but take it to your doctor and ask him what his opinion is especially in regards to your own case. Then, if you still don't feel good about it, ask Dr. Grattan to give you some feedback.

Hugs Josie!

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TRama Ex Member	Re: Statins have mast cell stabilising benifits Reply #6 - 02/15/11 at 04:44:47 Josie, Besides being a DMD, I'm an assistant lecturer on Pharmacology and Therapeutics. Despite doing less so than cimetidine, ranitidine is an inhibitor of an important metabolization cytochrome, which happens to be the same that metabolizes most statins.
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Josie

Ex Member

Re: Statins have mast cell stabilising benifits
Reply #7 - 02/15/11 at 09:19:26

Hi lisa and T rama ,

Thankyou .

I will use the cimetidine interactions as a guide . So my undersatnding of what you have said is that ranitidine blocks essensial chemicals that are required for statin breakdown , making me at higher risk of statin related side effects , myopthy in particular .

this information is vital for me to get the best treatment as i do have high cholesterol and that needs managing .

So if I need a stain I may ahve to loose Ranitidine , which will affect my mast cell problems as it is mopping up a lot of histamine . i will discuss it with my new immunologist and get his opinion as i know the diabetologists will want to deal with this .

I have found out today i was not tested for h pylori in Aug 08 , when I had an OGD , with the conclusion of gastritis . So it is possible I have and it as an underlying contributor to both stomach and gut angiodeama . This is another thing I will raise with the new immunologist

thanks again

Josie

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TRama

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Re: Statins have mast cell stabilising benifits
Reply #8 - 02/15/11 at 10:26:18

Josie,

It's precisely that.

If you have not had your helicobacter pilory tested, I would advise to do so before enrolling on statin therapy. If it comes out negative, and in the case you really need ranitidine, there are more recent H2 anti-histamines that do not seem to display such interactions.

As you probably know, since you are a nurse, there are better and more healthy ways to reduce your LDL levels, such as a balanced diet and exercise.

Tiago

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Josie

Ex Member

Re: Statins have mast cell stabilising benifits
Reply #9 - 02/15/11 at 23:45:19

Hi T rama ,

Thank you ,

Yes , I understand your points about diet and exercise . My diet is very healthy leading to local rabbits going without as i am eating all their greens and exercise is a challenge as I can only stand for a minute max on a good day . I also flush with any daytime activities .Don't worry I know you didn't know .

Thanks for the H pylori advice

So i may have to consider the other H2 meds as I have no other way to reduce it . Do you ahve any names

. My diabetic control remains poor due to insulin tolerence . I am on high units of lantus ( glargine ) . The diabetologist will make a decision on daytime short acting insulin . So better glycemic control will hopefully help the cholesterol .

I did see a paper connection mast cells to high cholesterol ???? So maybe a 2 way street . Ill dig it out .

Ramona mentioned that mast cell patients have high insulin tolerence , but didn't have a paper on it . I have searched extensively and can't find anything . Do you have anything on this ?. My diabetes was un masked by weight increase with steriods . I have lost the steriod weight now ( 42lb ) but i remain diabeteic .

This was diagnosed as steriod induced cushings , with diabetes as apart . i have been hypoadrenal since discontinuing high doses of prednislone last may ( 8 months 25mg plus , 9 weeks of higher doses . 11 IV doses 200 hydrocortisone with shock ) . I am maintained on 10mg hydrocortisone daily , increasing to 20mg in an infection . i am having high dose prednisalone for 3-6 days post shock then back to 20mg hydrocortisone for a week or 2 tapering to 10mg . My mast cell doc suspected underlying autoimmune addisons as its not common to loose adrenal function like this in 8 months . But tests have proved negative . i am aware of secondery hypoaldrenism , so I will discuss this with endocrinology / diabetologist when i see them . i have a 9am cortisol yesterday so interested in what that shows .

Thanks for you knowledge

Josie

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TRama

Ex Member

Re: Statins have mast cell stabilising benifits
Reply #10 - 02/16/11 at 07:59:44

Hi Josie,

I'm sorry, I really didn't know. I had to say it though...

I have never read anything about insulin tolerance in mastocytosis patients, and honestly, by heart, I honestly cannot tell the relation between them.

I don't like to comment on clinical info without the proper knowledge on patients, but your diabetes sounds secondary to steroids. That potential addison's is also strange. Did you slowly reduce the steroid dosages?

Tiago

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