Jump to content
RemedySpot.com

PST, Phenolsulfotransferase, Tylenol, autism- cellular metabolism problems.

Rate this topic


Guest guest

Recommended Posts

Guest guest

I have one daughter with Down syndrome, and I'm on a list with some super

amazing " professor Parents " .   Some of us are using Curcumin with our kids.  But

there is a new discussion of potential side effects for some kids, due to

possible depletion of PST.

Seems as

if Gingko Biloba (another helpful thing for those with Ds) may also affect PST.

In fact many DS nutritional and treatment protocols recommend using both

supplements.

 

a mom writes: " Owens

is a respected researcher in the field of sulfation and oxalates. This

was posted to many biomed autism lists the other day and she gave

permission...in fact highly approved of my posting it here. "     signed,  {name}

Herbal inhibitors of PST

    Posted by: " Owens "

    Date: Thu Jul 15, 2010 9:02 am ((PDT))

Listmates,

Phenolsulfotransferase activity was shown to be very deficient in autism

and some other conditions by research Dr. Rosemary Waring did in the

previous decade.  This is one of the strongest findings in autism with a p

value >0.00002.

It has only been in the last year when the public has finally been informed

of the serious nature of the effect of tylenol on this chemistry,

especially in children when they are vaccinated.

I think a lot of people lost track of Dr. Waring's finding in this area or

its potential significance in the last decade when people have thought more

of methylation, heavy metal detox and problems in oxidative stress.  In the

meantime, the use of herbs has picked up, especially for their antioxidant

capabilities.

Some of these herbs have been found to impair PST activity.  I thought it

would be important to see which herbs they are and the extent of their

potency in inhibiting PST.

The following study, available online, investigated the inhibition of

Sulfotransferase 1A3 (SULT1A3)

<http://www.jstage.jst.go.jp/article/bpb/32/1/105/_pdf>

These were the inhibitors they studied, in order by the potency of their

inhibition:

Green tea extract>>>

banaba extract>>

peanut seed coat extract>

gymnema

sylvestre>

St. 's wort>

Grape seed extract>

Gingko biloba>

milk thistle

Another study I've put below also found this PST inhibition in black tea.

I've put two other studies by Rosemary Waring below that help us understand

the significance of further compromising PST activity especially in the gut

when it is already weak.

Comments welcome!

Biol Psychiatry. 1999 Aug 1;46(3):420-4.

Sulphation deficit in " low-functioning " autistic children: a pilot study.

Alberti A, Pirrone P, Elia M, Waring RH, Romano C.

Department of Pediatrics, Oasi Institute for Research on Mental Retardation

and Brain Aging (IRCCS), Troina, Italy.

Abstract

BACKGROUND: Parents of autistic children and autism support groups often

report that autistic episodes are exacerbated when the children eat certain

foodstuffs such as dairy products, chocolates, wheat, corn sugar, apples,

and bananas. The hypothesis that autistic behavior might be related to

metabolic dysfunctions has led us to investigate in a group of " low

functioning " autistic children and in an age-matched control group each

made up of 20 subjects, the sulphation capacity available. METHODS:

Utilizing the biochemical characteristics of paracetamol we evaluated by

high performance liquid chromatography, the urine

paracetamol-sulfate/paracetamol-glucuronide (PS/PG) ratio in all subjects

following administration of this drug. RESULTS: The PS/PG ratio in the

group of autistic subjects gave a significantly lower results than the

control group with p < .00002. CONCLUSIONS: The inability to effectively

metabolize certain compounds particularly phenolic amines, toxic for the

CNS, could exacerbate the wide spectrum of autistic behavior.

PMID: 10435209 [PubMed - indexed for MEDLINE]

---------------------------------------------------

Biol Pharm Bull. 2009 Jan;32(1):105-9.

Inhibitory effects of herbal extracts on the activity of human

sulfotransferase isoform sulfotransferase 1A3 (SULT1A3).

Nagai M, Fukamachi T, Tsujimoto M, Ogura K, Hiratsuka A, Ohtani H, Hori S,

Sawada Y.

Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences,

The University of Tokyo, Japan.

Abstract

Sulfotransferase 1A3 (SULT1A3) is a phase II detoxifying enzyme of

xenobiotics predominantly expressed in the intestinal epithelium. Recent

increase in the use of herbal extracts as dietary supplements may lead to

an increase in the possibility of dietary supplement-drug interactions. The

purpose of the present study was to investigate the effects of 18 herbal

extracts on SULT1A3 activity and the possibility of interaction between

medicinal drugs and herbal extracts. We examined the inhibitory potencies

of 18 herbal extracts on the sulfation of dopamine, a typical substrate of

SULT1A3, and ritodrine, a beta(2) stimulant, by human recombinant SULT1A3.

The sulfation of dopamine was inhibited by extracts of banaba, green tea,

Rafuma, grape seed, peanut seed coat, gingko biloba leaf, St. 's wort,

gymnema and milkthistle. The IC(50) values of these herbal extracts were

lower than the putative gastrointestinal concentration when the recommended

dose was ingested. On the other hand, chlorella extract and rutin showed no

inhibitory effects and wheat, mulberry and siberian ginseng had IC(50)

values exceedingly higher than the putative gastrointestinal concentration.

The inhibitory profiles of herbal extracts for the sulfation of ritodrine

were comparable to those for the sulfation of dopamine. In conclusion, the

extracts of herbs such as banaba and green tea potently inhibited SULT1A3

activity. These extracts may increase the bioavailability of drugs whose

bioavailabilities were limited by the function of SULT1A3 on the intestinal

epithelium.

PMID: 19122289 [PubMed - indexed for MEDLINE]Free Article

----------------------------------------------------

Pharm Res. 2005 Aug;22(8):1406-10. Epub 2005 Aug 3.

Inhibitory effects of various beverages on ritodrine sulfation by

recombinant human sulfotransferase isoforms SULT1A1 and SULT1A3.

Nishimuta H, Tsujimoto M, Ogura K, Hiratsuka A, Ohtani H, Sawada Y.

Department of Medico-Pharmaceutical Sciences, Graduate School of

Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka-shi,

Fukuoka, 812-8582, Japan.

Abstract

PURPOSE: Ritodrine is known to undergo extensive presystemic sulfation in

the intestinal mucosa, and its bioavailability is as low as 30%.

Accordingly, inhibition of intestinal sulfation may lead to an increase in

the bioavailability of ritodrine. In this study, we aimed to investigate

the activities of ritodrine sulfation by SULT1A1, which is expressed

predominantly in the liver, and SULT1A3, which is expressed predominantly

in the intestine, as well as the inhibitory effects of beverages on their

activities. METHODS: We investigated ritodrine sulfation by using

recombinant human sulfotransferase (SULT) 1A1 and SULT1A3 in an in vitro

study. Next, we investigated the inhibitory effects of grapefruit juice,

orange juice, green tea, and black tea on ritodrine sulfation. RESULTS:

Sulfation of ritodrine by SULT1A3 was much higher than that by SULT1A1,

suggesting that the bioavailability of ritodrine may be limited by

intestinal SULT1A3. The ritodrine sulfation activities of SULT1A1 and

SULT1A3 were significantly inhibited by all beverages examined at a

concentration of 10%. Green tea and black tea exhibited potent inhibition;

even at a concentration of 5%, they both inhibited SULT1A1 by 100% and

SULT1A3 by >or=95%. CONCLUSION: Our results suggest that concomitant

ingestion of beverages such as green tea and black tea may increase the

bioavailability of orally administered ritodrine, and perhaps other

beta2-agonists, and lead to an increase in the clinical effects or adverse

reactions.

PMID: 16078151 [PubMed - indexed for MEDLINE]

-----------------------------------------------

J Agric Food Chem. 2003 Feb 26;51(5):1474-9.

Effects of phenolic acids on human phenolsulfotransferases in relation to

their antioxidant activity.

Yeh CT, Yen GC.

Department of Food Science, National Chung Hsing University, 250 Kuokuang

Road, Taichung 40227, Taiwan, Republic of China.

Abstract

Sulfate conjugation by phenolsulfotransferase (PST) enzyme is an important

process in the detoxification of xenobiotics and endogenous compounds.

There are two forms of PST that are specific for the sulfation of small

phenols (PST-P) and monoamines (PST-M). Phenoilc acids have been reported

to have important biological and pharmacological properties and may have

benefits to human health. In the present study, human platelets were used

as a model to investigate the influence of 13 phenolic acids on human PST

activity and to evaluate the relationship to their antioxidant activity.

The results showed that chlorogenic acid, syringic acid, protocatechuic

acid, vanillic acid, sinapic acid, and caffeic acid significantly (p <

0.05) inhibited the activities of both forms of PST by 21-30% at a

concentration of 6.7 microM. The activity of PST-P was enhanced (p < 0.05)

by p-hydroxybenzoic acid, gallic acid, gentisic acid, o-coumaric acid,

p-coumaric acid, and m-coumaric acid at a concentration of 6.7 microM,

whereas the activity of PST-M was enhanced by gentisic acid, gallic acid,

p-hydroxybenzoic acid, and ferulic acid. The phenolic acids exhibited

antioxidant activity as determined by the oxygen radical absorbance

capacity (ORAC) assay and Trolox equivalent antioxidant capacity (TEAC)

assay, especially gallic acid, p-hydroxybenzoic acid, gentisic acid, and

coumaric acid, which had strong activity. The overall effect of phenolic

acids tested on the activity of PST-P and PST-M was well correlated to

their antioxidant activity of ORAC value (r = 0.71, p < 0.01; and r = 0.66,

p < 0.01). These observations suggest that antioxidant phenolic acids might

alter sulfate conjugation.

PMID: 12590501 [PubMed - indexed for MEDLINE]

----------------------------------------------------

Curr Drug Metab. 2008 May;9(4):269-75.

Sulfotransferase inhibition: potential impact of diet and environmental

chemicals on steroid metabolism and drug detoxification.

RM, Waring RH.

School of Biosciences, University of Birmingham, Birmingham, UK.

R.M.@...

Abstract

The cytosolic sulfotransferase enzymes (SULT isoforms) utilise PAPS

(3'-phosphoadenosine-5'-phosphosulfate) as co-factor to transfer sulfonate

groups onto a wide range of substrates. SULT1A3 has catecholamines such as

dopamine as substrates while SULT 1E1 sulfonates oestrogens. SULT 1A1

sulfonates phenols and also oestrogens at a higher K(m) than SULT 1E1. SULT

2A1 mainly sulfonates DHEA and some steroids, with hydroxy derivatives of

polycyclic aromatic hydrocarbons. Studies on these isoforms with a range of

environmental chemicals and dietary components have shown that SULT 1A1 is

significantly inhibited by flavonoids; all flavones and flavonols with a

3',4'-dihydroxy motif had an IC(50) of < 100 nm against 3 microM

4-nitrophenol as the standard substrate. SULTs 1A3 and 2A1 were less

strongly inhibited by flavonoids or isoflavonoids although tricin

(3',5'-dimethoxy-4',5,7-trihydroxyflavone is a competitive inhibitor of

SULT 1E1 with an inhibition constant of approximately 1 nM. Fruit and

vegetable cytosols also inhibit SULT isoforms, as do long-chain

alkylphenols and chlorinated phenols. Phthalates (used as plasticisers)

inhibited SULTs 1E1 and 2A1. As these environmental contaminants and

dietary components all act at the same site, their effects would be

expected to be additive and could potentially therefore reduce sulfonation

of drugs and lead to altered pharmacological responses.

PMID: 18473744 [PubMed - indexed for MEDLINE]

---------------------------------------------

Life Sci. 2000 Sep 15;67(17):2051-7.

Activity of phenolsulfotransferases in the human gastrointestinal tract.

RM, Picton R, Singh S, Waring RH.

School of Biosciences, The University qf Birmingham, Edgbaston, UK.

Abstract

Sulfate conjugation by sulfotransferase enzymes is an important pathway for

the detoxication of xenobiotics and endogenous compounds. The large surface

area of the gastrointestinal tract exposes the body to a range of potential

toxins, and hence local metabolism is likely to be important. The ability

of different regions of the gut to sulfate micromolar concentrations of

simple phenols and catecholamines has been determined throughout the gut

using 4-nitrophenol and dopamine as standard substrates. The pattern of

sulfation of both compounds was similar, with activity highest in the small

bowel >right colon >left colon >rectum >stomach >esophagus. High

concentrations of sulfotransferases in the reservoir areas of the right and

left colon indicate possible importance in detoxication by sulfation and

also perhaps in activating mutagens in the same areas. Nutritional factors,

such as a high-fat diet may, however, alter sulfotransferase activity.

PMID: 11057755 [PubMed - indexed for MEDLINE]

Link to comment
Share on other sites

Guest guest

they need to start studying the 'high functioning' people with Autism.

>

> I have one daughter with Down syndrome, and I'm on a list with some super

amazing " professor Parents " .   Some of us are using Curcumin with our kids.  But

there is a new discussion of potential side effects for some kids, due to

possible depletion of PST.

>

> Seems as

> if Gingko Biloba (another helpful thing for those with Ds) may also affect

PST. In fact many DS nutritional and treatment protocols recommend using both

supplements.

>  

> a mom writes: " Owens

> is a respected researcher in the field of sulfation and oxalates. This

> was posted to many biomed autism lists the other day and she gave

> permission...in fact highly approved of my posting it here. "     signed, 

{name}

>

>

>

> Herbal inhibitors of PST

>     Posted by: " Owens "

>     Date: Thu Jul 15, 2010 9:02 am ((PDT))

>

> Listmates,

>

> Phenolsulfotransferase activity was shown to be very deficient in autism

> and some other conditions by research Dr. Rosemary Waring did in the

> previous decade.  This is one of the strongest findings in autism with a p

> value >0.00002.

>

> It has only been in the last year when the public has finally been informed

> of the serious nature of the effect of tylenol on this chemistry,

> especially in children when they are vaccinated.

>

> I think a lot of people lost track of Dr. Waring's finding in this area or

> its potential significance in the last decade when people have thought more

> of methylation, heavy metal detox and problems in oxidative stress.  In the

> meantime, the use of herbs has picked up, especially for their antioxidant

> capabilities.

>

> Some of these herbs have been found to impair PST activity.  I thought it

> would be important to see which herbs they are and the extent of their

> potency in inhibiting PST.

>

> The following study, available online, investigated the inhibition of

> Sulfotransferase 1A3 (SULT1A3)

>

> <http://www.jstage.jst.go.jp/article/bpb/32/1/105/_pdf>

>

> These were the inhibitors they studied, in order by the potency of their

> inhibition:

>

> Green tea extract>>>

> banaba extract>>

> peanut seed coat extract>

> gymnema

> sylvestre>

> St. 's wort>

> Grape seed extract>

> Gingko biloba>

> milk thistle

>

> Another study I've put below also found this PST inhibition in black tea.

>

> I've put two other studies by Rosemary Waring below that help us understand

> the significance of further compromising PST activity especially in the gut

> when it is already weak.

>

> Comments welcome!

>

>

>

>

>

> Biol Psychiatry. 1999 Aug 1;46(3):420-4.

>

> Sulphation deficit in " low-functioning " autistic children: a pilot study.

>

> Alberti A, Pirrone P, Elia M, Waring RH, Romano C.

>

> Department of Pediatrics, Oasi Institute for Research on Mental Retardation

> and Brain Aging (IRCCS), Troina, Italy.

>

> Abstract

>

> BACKGROUND: Parents of autistic children and autism support groups often

> report that autistic episodes are exacerbated when the children eat certain

> foodstuffs such as dairy products, chocolates, wheat, corn sugar, apples,

> and bananas. The hypothesis that autistic behavior might be related to

> metabolic dysfunctions has led us to investigate in a group of " low

> functioning " autistic children and in an age-matched control group each

> made up of 20 subjects, the sulphation capacity available. METHODS:

> Utilizing the biochemical characteristics of paracetamol we evaluated by

> high performance liquid chromatography, the urine

> paracetamol-sulfate/paracetamol-glucuronide (PS/PG) ratio in all subjects

> following administration of this drug. RESULTS: The PS/PG ratio in the

> group of autistic subjects gave a significantly lower results than the

> control group with p < .00002. CONCLUSIONS: The inability to effectively

> metabolize certain compounds particularly phenolic amines, toxic for the

> CNS, could exacerbate the wide spectrum of autistic behavior.

>

> PMID: 10435209 [PubMed - indexed for MEDLINE]

>

>

> ---------------------------------------------------

>

> Biol Pharm Bull. 2009 Jan;32(1):105-9.

>

> Inhibitory effects of herbal extracts on the activity of human

> sulfotransferase isoform sulfotransferase 1A3 (SULT1A3).

>

> Nagai M, Fukamachi T, Tsujimoto M, Ogura K, Hiratsuka A, Ohtani H, Hori S,

> Sawada Y.

>

> Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences,

> The University of Tokyo, Japan.

>

> Abstract

>

> Sulfotransferase 1A3 (SULT1A3) is a phase II detoxifying enzyme of

> xenobiotics predominantly expressed in the intestinal epithelium. Recent

> increase in the use of herbal extracts as dietary supplements may lead to

> an increase in the possibility of dietary supplement-drug interactions. The

> purpose of the present study was to investigate the effects of 18 herbal

> extracts on SULT1A3 activity and the possibility of interaction between

> medicinal drugs and herbal extracts. We examined the inhibitory potencies

> of 18 herbal extracts on the sulfation of dopamine, a typical substrate of

> SULT1A3, and ritodrine, a beta(2) stimulant, by human recombinant SULT1A3.

> The sulfation of dopamine was inhibited by extracts of banaba, green tea,

> Rafuma, grape seed, peanut seed coat, gingko biloba leaf, St. 's wort,

> gymnema and milkthistle. The IC(50) values of these herbal extracts were

> lower than the putative gastrointestinal concentration when the recommended

> dose was ingested. On the other hand, chlorella extract and rutin showed no

> inhibitory effects and wheat, mulberry and siberian ginseng had IC(50)

> values exceedingly higher than the putative gastrointestinal concentration.

> The inhibitory profiles of herbal extracts for the sulfation of ritodrine

> were comparable to those for the sulfation of dopamine. In conclusion, the

> extracts of herbs such as banaba and green tea potently inhibited SULT1A3

> activity. These extracts may increase the bioavailability of drugs whose

> bioavailabilities were limited by the function of SULT1A3 on the intestinal

> epithelium.

>

> PMID: 19122289 [PubMed - indexed for MEDLINE]Free Article

>

> ----------------------------------------------------

>

> Pharm Res. 2005 Aug;22(8):1406-10. Epub 2005 Aug 3.

>

> Inhibitory effects of various beverages on ritodrine sulfation by

> recombinant human sulfotransferase isoforms SULT1A1 and SULT1A3.

>

> Nishimuta H, Tsujimoto M, Ogura K, Hiratsuka A, Ohtani H, Sawada Y.

>

> Department of Medico-Pharmaceutical Sciences, Graduate School of

> Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka-shi,

> Fukuoka, 812-8582, Japan.

>

> Abstract

>

> PURPOSE: Ritodrine is known to undergo extensive presystemic sulfation in

> the intestinal mucosa, and its bioavailability is as low as 30%.

> Accordingly, inhibition of intestinal sulfation may lead to an increase in

> the bioavailability of ritodrine. In this study, we aimed to investigate

> the activities of ritodrine sulfation by SULT1A1, which is expressed

> predominantly in the liver, and SULT1A3, which is expressed predominantly

> in the intestine, as well as the inhibitory effects of beverages on their

> activities. METHODS: We investigated ritodrine sulfation by using

> recombinant human sulfotransferase (SULT) 1A1 and SULT1A3 in an in vitro

> study. Next, we investigated the inhibitory effects of grapefruit juice,

> orange juice, green tea, and black tea on ritodrine sulfation. RESULTS:

> Sulfation of ritodrine by SULT1A3 was much higher than that by SULT1A1,

> suggesting that the bioavailability of ritodrine may be limited by

> intestinal SULT1A3. The ritodrine sulfation activities of SULT1A1 and

> SULT1A3 were significantly inhibited by all beverages examined at a

> concentration of 10%. Green tea and black tea exhibited potent inhibition;

> even at a concentration of 5%, they both inhibited SULT1A1 by 100% and

> SULT1A3 by >or=95%. CONCLUSION: Our results suggest that concomitant

> ingestion of beverages such as green tea and black tea may increase the

> bioavailability of orally administered ritodrine, and perhaps other

> beta2-agonists, and lead to an increase in the clinical effects or adverse

> reactions.

>

> PMID: 16078151 [PubMed - indexed for MEDLINE]

>

> -----------------------------------------------

>

> J Agric Food Chem. 2003 Feb 26;51(5):1474-9.

>

> Effects of phenolic acids on human phenolsulfotransferases in relation to

> their antioxidant activity.

>

> Yeh CT, Yen GC.

>

> Department of Food Science, National Chung Hsing University, 250 Kuokuang

> Road, Taichung 40227, Taiwan, Republic of China.

>

> Abstract

>

> Sulfate conjugation by phenolsulfotransferase (PST) enzyme is an important

> process in the detoxification of xenobiotics and endogenous compounds.

> There are two forms of PST that are specific for the sulfation of small

> phenols (PST-P) and monoamines (PST-M). Phenoilc acids have been reported

> to have important biological and pharmacological properties and may have

> benefits to human health. In the present study, human platelets were used

> as a model to investigate the influence of 13 phenolic acids on human PST

> activity and to evaluate the relationship to their antioxidant activity.

> The results showed that chlorogenic acid, syringic acid, protocatechuic

> acid, vanillic acid, sinapic acid, and caffeic acid significantly (p <

> 0.05) inhibited the activities of both forms of PST by 21-30% at a

> concentration of 6.7 microM. The activity of PST-P was enhanced (p < 0.05)

> by p-hydroxybenzoic acid, gallic acid, gentisic acid, o-coumaric acid,

> p-coumaric acid, and m-coumaric acid at a concentration of 6.7 microM,

> whereas the activity of PST-M was enhanced by gentisic acid, gallic acid,

> p-hydroxybenzoic acid, and ferulic acid. The phenolic acids exhibited

> antioxidant activity as determined by the oxygen radical absorbance

> capacity (ORAC) assay and Trolox equivalent antioxidant capacity (TEAC)

> assay, especially gallic acid, p-hydroxybenzoic acid, gentisic acid, and

> coumaric acid, which had strong activity. The overall effect of phenolic

> acids tested on the activity of PST-P and PST-M was well correlated to

> their antioxidant activity of ORAC value (r = 0.71, p < 0.01; and r = 0.66,

> p < 0.01). These observations suggest that antioxidant phenolic acids might

> alter sulfate conjugation.

>

> PMID: 12590501 [PubMed - indexed for MEDLINE]

>

> ----------------------------------------------------

>

> Curr Drug Metab. 2008 May;9(4):269-75.

>

> Sulfotransferase inhibition: potential impact of diet and environmental

> chemicals on steroid metabolism and drug detoxification.

>

> RM, Waring RH.

>

> School of Biosciences, University of Birmingham, Birmingham, UK.

> R.M.@...

>

> Abstract

>

> The cytosolic sulfotransferase enzymes (SULT isoforms) utilise PAPS

> (3'-phosphoadenosine-5'-phosphosulfate) as co-factor to transfer sulfonate

> groups onto a wide range of substrates. SULT1A3 has catecholamines such as

> dopamine as substrates while SULT 1E1 sulfonates oestrogens. SULT 1A1

> sulfonates phenols and also oestrogens at a higher K(m) than SULT 1E1. SULT

> 2A1 mainly sulfonates DHEA and some steroids, with hydroxy derivatives of

> polycyclic aromatic hydrocarbons. Studies on these isoforms with a range of

> environmental chemicals and dietary components have shown that SULT 1A1 is

> significantly inhibited by flavonoids; all flavones and flavonols with a

> 3',4'-dihydroxy motif had an IC(50) of < 100 nm against 3 microM

> 4-nitrophenol as the standard substrate. SULTs 1A3 and 2A1 were less

> strongly inhibited by flavonoids or isoflavonoids although tricin

> (3',5'-dimethoxy-4',5,7-trihydroxyflavone is a competitive inhibitor of

> SULT 1E1 with an inhibition constant of approximately 1 nM. Fruit and

> vegetable cytosols also inhibit SULT isoforms, as do long-chain

> alkylphenols and chlorinated phenols. Phthalates (used as plasticisers)

> inhibited SULTs 1E1 and 2A1. As these environmental contaminants and

> dietary components all act at the same site, their effects would be

> expected to be additive and could potentially therefore reduce sulfonation

> of drugs and lead to altered pharmacological responses.

>

> PMID: 18473744 [PubMed - indexed for MEDLINE]

>

> ---------------------------------------------

>

> Life Sci. 2000 Sep 15;67(17):2051-7.

>

> Activity of phenolsulfotransferases in the human gastrointestinal tract.

>

> RM, Picton R, Singh S, Waring RH.

>

> School of Biosciences, The University qf Birmingham, Edgbaston, UK.

>

> Abstract

>

> Sulfate conjugation by sulfotransferase enzymes is an important pathway for

> the detoxication of xenobiotics and endogenous compounds. The large surface

> area of the gastrointestinal tract exposes the body to a range of potential

> toxins, and hence local metabolism is likely to be important. The ability

> of different regions of the gut to sulfate micromolar concentrations of

> simple phenols and catecholamines has been determined throughout the gut

> using 4-nitrophenol and dopamine as standard substrates. The pattern of

> sulfation of both compounds was similar, with activity highest in the small

> bowel >right colon >left colon >rectum >stomach >esophagus. High

> concentrations of sulfotransferases in the reservoir areas of the right and

> left colon indicate possible importance in detoxication by sulfation and

> also perhaps in activating mutagens in the same areas. Nutritional factors,

> such as a high-fat diet may, however, alter sulfotransferase activity.

>

> PMID: 11057755 [PubMed - indexed for MEDLINE]

>

>

>

>

>

Link to comment
Share on other sites

Guest guest

On what list are they talking about enhansa and negative side effects. We tried

it on our daught who has a lot of phenol/salicylate problems. We ending quitting

Enhansa for now, but I would like to learn more. Doris

>

> I have one daughter with Down syndrome, and I'm on a list with some super

amazing " professor Parents " .   Some of us are using Curcumin with our kids.  But

there is a new discussion of potential side effects for some kids, due to

possible depletion of PST.

>

> Seems as

> if Gingko Biloba (another helpful thing for those with Ds) may also affect

PST. In fact many DS nutritional and treatment protocols recommend using both

supplements.

>  

> a mom writes: " Owens

> is a respected researcher in the field of sulfation and oxalates. This

> was posted to many biomed autism lists the other day and she gave

> permission...in fact highly approved of my posting it here. "     signed, 

{name}

>

>

>

> Herbal inhibitors of PST

>     Posted by: " Owens "

>     Date: Thu Jul 15, 2010 9:02 am ((PDT))

>

> Listmates,

>

> Phenolsulfotransferase activity was shown to be very deficient in autism

> and some other conditions by research Dr. Rosemary Waring did in the

> previous decade.  This is one of the strongest findings in autism with a p

> value >0.00002.

>

> It has only been in the last year when the public has finally been informed

> of the serious nature of the effect of tylenol on this chemistry,

> especially in children when they are vaccinated.

>

> I think a lot of people lost track of Dr. Waring's finding in this area or

> its potential significance in the last decade when people have thought more

> of methylation, heavy metal detox and problems in oxidative stress.  In the

> meantime, the use of herbs has picked up, especially for their antioxidant

> capabilities.

>

> Some of these herbs have been found to impair PST activity.  I thought it

> would be important to see which herbs they are and the extent of their

> potency in inhibiting PST.

>

> The following study, available online, investigated the inhibition of

> Sulfotransferase 1A3 (SULT1A3)

>

> <http://www.jstage.jst.go.jp/article/bpb/32/1/105/_pdf>

>

> These were the inhibitors they studied, in order by the potency of their

> inhibition:

>

> Green tea extract>>>

> banaba extract>>

> peanut seed coat extract>

> gymnema

> sylvestre>

> St. 's wort>

> Grape seed extract>

> Gingko biloba>

> milk thistle

>

> Another study I've put below also found this PST inhibition in black tea.

>

> I've put two other studies by Rosemary Waring below that help us understand

> the significance of further compromising PST activity especially in the gut

> when it is already weak.

>

> Comments welcome!

>

>

>

>

>

> Biol Psychiatry. 1999 Aug 1;46(3):420-4.

>

> Sulphation deficit in " low-functioning " autistic children: a pilot study.

>

> Alberti A, Pirrone P, Elia M, Waring RH, Romano C.

>

> Department of Pediatrics, Oasi Institute for Research on Mental Retardation

> and Brain Aging (IRCCS), Troina, Italy.

>

> Abstract

>

> BACKGROUND: Parents of autistic children and autism support groups often

> report that autistic episodes are exacerbated when the children eat certain

> foodstuffs such as dairy products, chocolates, wheat, corn sugar, apples,

> and bananas. The hypothesis that autistic behavior might be related to

> metabolic dysfunctions has led us to investigate in a group of " low

> functioning " autistic children and in an age-matched control group each

> made up of 20 subjects, the sulphation capacity available. METHODS:

> Utilizing the biochemical characteristics of paracetamol we evaluated by

> high performance liquid chromatography, the urine

> paracetamol-sulfate/paracetamol-glucuronide (PS/PG) ratio in all subjects

> following administration of this drug. RESULTS: The PS/PG ratio in the

> group of autistic subjects gave a significantly lower results than the

> control group with p < .00002. CONCLUSIONS: The inability to effectively

> metabolize certain compounds particularly phenolic amines, toxic for the

> CNS, could exacerbate the wide spectrum of autistic behavior.

>

> PMID: 10435209 [PubMed - indexed for MEDLINE]

>

>

> ---------------------------------------------------

>

> Biol Pharm Bull. 2009 Jan;32(1):105-9.

>

> Inhibitory effects of herbal extracts on the activity of human

> sulfotransferase isoform sulfotransferase 1A3 (SULT1A3).

>

> Nagai M, Fukamachi T, Tsujimoto M, Ogura K, Hiratsuka A, Ohtani H, Hori S,

> Sawada Y.

>

> Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences,

> The University of Tokyo, Japan.

>

> Abstract

>

> Sulfotransferase 1A3 (SULT1A3) is a phase II detoxifying enzyme of

> xenobiotics predominantly expressed in the intestinal epithelium. Recent

> increase in the use of herbal extracts as dietary supplements may lead to

> an increase in the possibility of dietary supplement-drug interactions. The

> purpose of the present study was to investigate the effects of 18 herbal

> extracts on SULT1A3 activity and the possibility of interaction between

> medicinal drugs and herbal extracts. We examined the inhibitory potencies

> of 18 herbal extracts on the sulfation of dopamine, a typical substrate of

> SULT1A3, and ritodrine, a beta(2) stimulant, by human recombinant SULT1A3.

> The sulfation of dopamine was inhibited by extracts of banaba, green tea,

> Rafuma, grape seed, peanut seed coat, gingko biloba leaf, St. 's wort,

> gymnema and milkthistle. The IC(50) values of these herbal extracts were

> lower than the putative gastrointestinal concentration when the recommended

> dose was ingested. On the other hand, chlorella extract and rutin showed no

> inhibitory effects and wheat, mulberry and siberian ginseng had IC(50)

> values exceedingly higher than the putative gastrointestinal concentration.

> The inhibitory profiles of herbal extracts for the sulfation of ritodrine

> were comparable to those for the sulfation of dopamine. In conclusion, the

> extracts of herbs such as banaba and green tea potently inhibited SULT1A3

> activity. These extracts may increase the bioavailability of drugs whose

> bioavailabilities were limited by the function of SULT1A3 on the intestinal

> epithelium.

>

> PMID: 19122289 [PubMed - indexed for MEDLINE]Free Article

>

> ----------------------------------------------------

>

> Pharm Res. 2005 Aug;22(8):1406-10. Epub 2005 Aug 3.

>

> Inhibitory effects of various beverages on ritodrine sulfation by

> recombinant human sulfotransferase isoforms SULT1A1 and SULT1A3.

>

> Nishimuta H, Tsujimoto M, Ogura K, Hiratsuka A, Ohtani H, Sawada Y.

>

> Department of Medico-Pharmaceutical Sciences, Graduate School of

> Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka-shi,

> Fukuoka, 812-8582, Japan.

>

> Abstract

>

> PURPOSE: Ritodrine is known to undergo extensive presystemic sulfation in

> the intestinal mucosa, and its bioavailability is as low as 30%.

> Accordingly, inhibition of intestinal sulfation may lead to an increase in

> the bioavailability of ritodrine. In this study, we aimed to investigate

> the activities of ritodrine sulfation by SULT1A1, which is expressed

> predominantly in the liver, and SULT1A3, which is expressed predominantly

> in the intestine, as well as the inhibitory effects of beverages on their

> activities. METHODS: We investigated ritodrine sulfation by using

> recombinant human sulfotransferase (SULT) 1A1 and SULT1A3 in an in vitro

> study. Next, we investigated the inhibitory effects of grapefruit juice,

> orange juice, green tea, and black tea on ritodrine sulfation. RESULTS:

> Sulfation of ritodrine by SULT1A3 was much higher than that by SULT1A1,

> suggesting that the bioavailability of ritodrine may be limited by

> intestinal SULT1A3. The ritodrine sulfation activities of SULT1A1 and

> SULT1A3 were significantly inhibited by all beverages examined at a

> concentration of 10%. Green tea and black tea exhibited potent inhibition;

> even at a concentration of 5%, they both inhibited SULT1A1 by 100% and

> SULT1A3 by >or=95%. CONCLUSION: Our results suggest that concomitant

> ingestion of beverages such as green tea and black tea may increase the

> bioavailability of orally administered ritodrine, and perhaps other

> beta2-agonists, and lead to an increase in the clinical effects or adverse

> reactions.

>

> PMID: 16078151 [PubMed - indexed for MEDLINE]

>

> -----------------------------------------------

>

> J Agric Food Chem. 2003 Feb 26;51(5):1474-9.

>

> Effects of phenolic acids on human phenolsulfotransferases in relation to

> their antioxidant activity.

>

> Yeh CT, Yen GC.

>

> Department of Food Science, National Chung Hsing University, 250 Kuokuang

> Road, Taichung 40227, Taiwan, Republic of China.

>

> Abstract

>

> Sulfate conjugation by phenolsulfotransferase (PST) enzyme is an important

> process in the detoxification of xenobiotics and endogenous compounds.

> There are two forms of PST that are specific for the sulfation of small

> phenols (PST-P) and monoamines (PST-M). Phenoilc acids have been reported

> to have important biological and pharmacological properties and may have

> benefits to human health. In the present study, human platelets were used

> as a model to investigate the influence of 13 phenolic acids on human PST

> activity and to evaluate the relationship to their antioxidant activity.

> The results showed that chlorogenic acid, syringic acid, protocatechuic

> acid, vanillic acid, sinapic acid, and caffeic acid significantly (p <

> 0.05) inhibited the activities of both forms of PST by 21-30% at a

> concentration of 6.7 microM. The activity of PST-P was enhanced (p < 0.05)

> by p-hydroxybenzoic acid, gallic acid, gentisic acid, o-coumaric acid,

> p-coumaric acid, and m-coumaric acid at a concentration of 6.7 microM,

> whereas the activity of PST-M was enhanced by gentisic acid, gallic acid,

> p-hydroxybenzoic acid, and ferulic acid. The phenolic acids exhibited

> antioxidant activity as determined by the oxygen radical absorbance

> capacity (ORAC) assay and Trolox equivalent antioxidant capacity (TEAC)

> assay, especially gallic acid, p-hydroxybenzoic acid, gentisic acid, and

> coumaric acid, which had strong activity. The overall effect of phenolic

> acids tested on the activity of PST-P and PST-M was well correlated to

> their antioxidant activity of ORAC value (r = 0.71, p < 0.01; and r = 0.66,

> p < 0.01). These observations suggest that antioxidant phenolic acids might

> alter sulfate conjugation.

>

> PMID: 12590501 [PubMed - indexed for MEDLINE]

>

> ----------------------------------------------------

>

> Curr Drug Metab. 2008 May;9(4):269-75.

>

> Sulfotransferase inhibition: potential impact of diet and environmental

> chemicals on steroid metabolism and drug detoxification.

>

> RM, Waring RH.

>

> School of Biosciences, University of Birmingham, Birmingham, UK.

> R.M.@...

>

> Abstract

>

> The cytosolic sulfotransferase enzymes (SULT isoforms) utilise PAPS

> (3'-phosphoadenosine-5'-phosphosulfate) as co-factor to transfer sulfonate

> groups onto a wide range of substrates. SULT1A3 has catecholamines such as

> dopamine as substrates while SULT 1E1 sulfonates oestrogens. SULT 1A1

> sulfonates phenols and also oestrogens at a higher K(m) than SULT 1E1. SULT

> 2A1 mainly sulfonates DHEA and some steroids, with hydroxy derivatives of

> polycyclic aromatic hydrocarbons. Studies on these isoforms with a range of

> environmental chemicals and dietary components have shown that SULT 1A1 is

> significantly inhibited by flavonoids; all flavones and flavonols with a

> 3',4'-dihydroxy motif had an IC(50) of < 100 nm against 3 microM

> 4-nitrophenol as the standard substrate. SULTs 1A3 and 2A1 were less

> strongly inhibited by flavonoids or isoflavonoids although tricin

> (3',5'-dimethoxy-4',5,7-trihydroxyflavone is a competitive inhibitor of

> SULT 1E1 with an inhibition constant of approximately 1 nM. Fruit and

> vegetable cytosols also inhibit SULT isoforms, as do long-chain

> alkylphenols and chlorinated phenols. Phthalates (used as plasticisers)

> inhibited SULTs 1E1 and 2A1. As these environmental contaminants and

> dietary components all act at the same site, their effects would be

> expected to be additive and could potentially therefore reduce sulfonation

> of drugs and lead to altered pharmacological responses.

>

> PMID: 18473744 [PubMed - indexed for MEDLINE]

>

> ---------------------------------------------

>

> Life Sci. 2000 Sep 15;67(17):2051-7.

>

> Activity of phenolsulfotransferases in the human gastrointestinal tract.

>

> RM, Picton R, Singh S, Waring RH.

>

> School of Biosciences, The University qf Birmingham, Edgbaston, UK.

>

> Abstract

>

> Sulfate conjugation by sulfotransferase enzymes is an important pathway for

> the detoxication of xenobiotics and endogenous compounds. The large surface

> area of the gastrointestinal tract exposes the body to a range of potential

> toxins, and hence local metabolism is likely to be important. The ability

> of different regions of the gut to sulfate micromolar concentrations of

> simple phenols and catecholamines has been determined throughout the gut

> using 4-nitrophenol and dopamine as standard substrates. The pattern of

> sulfation of both compounds was similar, with activity highest in the small

> bowel >right colon >left colon >rectum >stomach >esophagus. High

> concentrations of sulfotransferases in the reservoir areas of the right and

> left colon indicate possible importance in detoxication by sulfation and

> also perhaps in activating mutagens in the same areas. Nutritional factors,

> such as a high-fat diet may, however, alter sulfotransferase activity.

>

> PMID: 11057755 [PubMed - indexed for MEDLINE]

>

>

>

>

>

Link to comment
Share on other sites

Join the conversation

You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.

Loading...
×
×
  • Create New...