RE : Re: RE : Re: I'd never heard of Welchol (Enterohepatic recirculation of mycotoxins)

[Guest guest]

That was a great explanation; the process of attaching with a 'charge' to carry

out the small molecular weight toxins. I did not fully understand the process.

Does WelChol operate the same way? I do not take it at the same time as my

other supplements.

The citations you provided were excellent.

Did I understand in the French article that the Aspartame 'enhanced' the

" transit " of the toxins in some manner? I could not get my head completely

around the process.

It IS amazing the lengths attempted in the agrarian/farm context to rid animals

of these toxins...

LiveSimply <quackadillian@...> a écrit :

Ginlol,

As I understand it, Cholestyramine is COMPLETELY different than

fiber/laxatives. It *binds* with mycotoxins.

Its what's known as a bile acid sequestrant. It interrupts the cycle

of enterohepatic recirculation that keep mycotoxins going around and

around again in the body.

Anion exchange resins like cholestyramine mix with your food and bile

in the small intestine and the cholestyramine resin, which carries a

small electric charge literally attaches to the small molecular weight

biotoxins and turns them into solids that are excreted. Its the only

way to non-invasively remove them that I know of.

This is what happens.. (references below) You can go to PubMed and

plug their PMIDs into the system easily to get the related papers.

These came back from a search for 'enterohepatic mycotoxin' (without

the quotes)

People sometimes take laxatives after they have taken cholestyramine.

Maybe thats why some people confuse the two. But they do different

things completely. A laxative is not going to remove the toxins from

your bile or prevent their reabsorbtion. (I suspect that it would have

to be a VERY good laxative to do that, so good that you would not get

any value from the food you ate AT ALL. Cholestyramine, etc. are

specific removers of a relatively small number of things that includes

mycotoxins.)

. . . . . . . .

J Food Prot. 1999 Dec;62(12):1461-5.

Related Articles, Links

Cholestyramine protection against ochratoxin A toxicity: role of

ochratoxin A sorption by the resin and bile acid enterohepatic

circulation.

Kerkadi A, Barriault C, Marquardt RR, Frohlich AA, Yousef IM, Zhu

XX, Tuchweber B.

Department of Nutrition, Université de Montréal, Québec, Canada.

We have shown that the addition of cholestyramine (CHA, a resin

known to bind bile salts in the gastrointestinal tract) to ochratoxin

A (OTA)-contaminated rat diets reduced plasma levels of the toxin and

prevented OTA-induced nephrotoxicity. To elucidate the mechanism of

action of CHA, we carried out in vitro experiments to determine

whether the resin may bind the toxin. For comparative purposes,

binding of bile salts to the resin was also examined. Results showed

that CHA binds both OTA and bile salts (taurodeoxycholate [TDC] and

taurocholate [TCA]). Also, CHA showed greater affinity for OTA and TDC

than for TCA. At 1 mM concentration, 96% of OTA and 80% of TDC were

bound to the resin, while for TCA binding was only 50%. However,

saturation of the resin was reached at higher levels with bile acids

compared to OTA (3.67 mmol/g resin for TCA and 3.71 mmol/g resin for

TDC versus 2.85 mmol/g resin for OTA). To characterize the nature of

the binding of the toxin to CHA, NaCl (0 to 200 mM) was added to a

fixed amount of OTA or bile acids. As expected, TCA absorption was

decreased by the addition of NaCl (<50 mM), indicating electrostatic

binding. However, OTA and TDC sorption was decreased only at high

concentrations of NaCl (>150 mM), suggesting a stronger binding to the

resin than that shown with TCA. Sequential competitive studies

demonstrated that CHA binds more OTA than TCA. The results of the in

vivo study show the role of bile salts in OTA absorption. The toxin's

plasma levels at 1 and 3 h after a single oral dose of OTA were

significantly decreased in bile salt-depleted rats compared to the

control. Thus, the alteration of the bile salt biliary pool and OTA

enterohepatic circulation may be an additional mechanism of action of

the resin against mycotoxin toxicity.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 10606152 [PubMed - indexed for MEDLINE]

J Toxicol Environ Health A. 1998 Feb 6;53(3):231-50.

Related Articles, Links

Dietary cholestyramine reduces ochratoxin A-induced nephrotoxicity

in the rat by decreasing plasma levels and enhancing fecal excretion

of the toxin.

Kerkadi A, Barriault C, Tuchweber B, Frohlich AA, Marquardt RR,

Bouchard G, Yousef IM.

Département de Nutrition, Université de Montréal, Québec, Canada.

Ochratoxin A (OTA) is a mycotoxin that may contaminate animal feed

(oat, barley, and rye) and food (wheat, rice, coffee, beer, pig meat),

leading to major health problems (e.g., nephropathy) in several animal

species including humans. Several methods have been tested to reduce

the toxicity of OTA in animals but with limited success. In rats, the

effect of cholestyramine (CHA), a bile acid-binding resin, was

investigated on OTA-induced nephrotoxicity and bioavailability.

Animals were fed semisynthetic diets containing two levels of OTA: 1

or 3 ppm. At each level of OTA, the diets were enriched with 0.1, 1,

and 5% of CHA. The results showed that CHA decreased the concentration

of OTA in plasma. At 1 and 3 ppm of OTA in the diet, CHA is effective

at a level of 0.1% and 5%, respectively. The excretion of OTA and its

metabolites (ochratoxin alpha and hydroxylated ochratoxin A) in bile

and urine was also decreased by addition of 5% CHA in the diet. This

was associated with an increase of OTA excretion in feces. Enzymuria

and renal morphology revealed that dietary CHA can decrease

OTA-induced nephrotoxicity, probably by reducing renal exposure to the

toxin. In conclusion, CHA can reduce OTA concentrations in plasma as

well as reducing nephrotoxicity, which may be attributed to a decrease

of bioavailability and/or enterohepatic circulation of the toxin.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 9482354 [PubMed - indexed for MEDLINE]

Nat Toxins. 1994;2(2):73-80.

Related Articles, Links

Pharmacokinetic fate of 14C-labelled fumonisin B1 in swine.

Prelusky DB, Trenholm HL, Savard ME.

Centre for Food and Animal Research, Agriculture Canada, Central

Experimental Farm, Ottawa.

The pharmacokinetics of the mycotoxin fumonisn B1 (FB1) were

investigated in pigs. Animals were administered 14C-FB1 intravenously

(IV; 0.25 microCi, 0.40 mg/kg) or intragastrically (IG; 0.35 microCi,

0.50 mg/kg); separate groups of pigs underwent bile cannulation prior

to dosing (groups IV/B and IG/B, respectively). Blood, urine, faeces,

(and bile), were collected at specific time intervals over 72 hr, and

assayed for specific activity. Following IV dosing, plasma

concentration-time profiles were triexponential, with the following

mean values: t1/2 alpha, 2.2 min; t1/2 beta, 10.5 min; t1/2 gamma, 182

min; apparent volume distribution (Vd gamma), 2.4 l kg-1; plasma

clearance, 9.1 ml min-1 kg-1. After 3 days, clearance of FB1-derived

radioactivity from the body had slowed to trace levels; total

recoveries in urine and faeces were 21.2% and 58.3%, respectively. In

bile-interrupted pigs (IV/B) the absence of the slow terminal

elimination phase (gamma) suggested FB1 underwent enterohepatic

circulation. Biliary recovery was 70.8% of the IV-dose. Radioactivity

remaining in tissues after 72 hr amounted to 19.8% and 11.9% of the

dose given to IV and IV/B pigs, respectively; highest activities were

measured in liver and kidney equivalent to 1,076 and 486 ng FB1 and/or

metabolites per g tissue, respectively. Based on plasma and excretion

data, systemic bioavailability following IG dosing was estimated to be

a very limited 3-6%. Tissue residue levels following IG dosing were

10-20-fold less than IV dosing.

PMID: 8075896 [PubMed - indexed for MEDLINE]

Toxicol Appl Pharmacol. 1993 Jul;121(1):152-9.

Related Articles, Links

Click here to read

Biliary excretion and enterohepatic cycling of zearalenone in immature

pigs.

Biehl ML, Prelusky DB, Koritz GD, Hartin KE, Buck WB, Trenholm HL.

Department of Veterinary Biosciences, College of Veterinary

Medicine, University of Illinois, Urbana 61801.

The disposition of the estrogenic mycotoxin, zearalenone (ZEN) in

female, 10- to 14-week-old Yorkshire pigs was investigated. Pigs were

administered [3H]ZEN intravenously (IV; n = 4; 5 mg/kg; 15

microCi/kg), orally (n = 4; 10 mg/kg; 30 microCi/kg), or intravenously

with bile removal (IVB; n = 2; 5 mg/kg; 15 microCi/kg). Plasma, urine,

feces, and bile (IVB pigs only) were serially collected and analyzed

for radioactivity. Metabolite profiles were determined in plasma and

bile by HPLC. The biological half-life of total plasma radioactivity

in IV and orally dosed pigs (86.6 hr) was much larger than that of IVB

animals (3.34 hr). Metabolite profiles of plasma concentration vs time

demonstrated secondary peaks in concentration during the terminal

elimination phase in IV and orally dosed pigs. In IVB pigs these peaks

were absent, relative metabolite profiles were altered, and ZEN and

metabolites were no longer detectable after 16 hr post-dosing. Biliary

recovery of radioactivity, principally as glucuronide conjugates, was

extensive (45.61 +/- 4.7%) in IVB pigs and significantly greater (p <

0.05) than that of fecal recovery of radioactivity in IV (6.56 +/-

0.78) or orally dosed (21.74 +/- 1.56%) pigs. Intraduodenal

administration of bile containing [3H]ZEN and metabolites resulted in

recovery of 64.56 +/- 4.89% of the dose in bile, 20.78 +/- 3.94% in

urine, and the presence of glucuronide conjugates of ZEN and

alpha-zearalenol (ZEL) in portal and jugular plasma. Differences in

metabolite profiles between administered bile and sampled plasma

suggest that the intestinal mucosa was active in reducing ZEN to ZEL

and conjugating these metabolites with glucuronic acid. These studies

provide evidence for extensive biliary secretion and enterohepatic

cycling of ZEN and metabolites in pigs.

PMID: 8337696 [PubMed - indexed for MEDLINE]

J Anim Sci. 1992 Dec;70(12):3968-88.

Related Articles, Links

Click here to read

A review of recent advances in understanding ochratoxicosis.

Marquardt RR, Frohlich AA.

Department of Animal Science, University of Manitoba, Winnipeg, Canada.

Ochratoxin A (OA) is a toxin that contains an isocoumarin moiety

linked by a peptide bond to phenylalanine. It is produced by certain

Penicillium (mainly P. verrucosum) and Aspergillus (mainly A.

alutaceus) species of storage fungi. Total amounts of OA and other

related toxins produced by these fungi are influenced by many factors.

Several forms of OA have been discovered, some of which are highly

toxic, whereas others have lower toxicity. Ochratoxin A has been

detected in foods, feeds, animal tissues, and human blood in both

Europe and North America. It has been implicated in the fatal human

disease Balkan endemic nephropathy, has been shown to be a powerful

carcinogen in rodents, and produces many other adverse effects in

animals. It is absorbed passively throughout the gastrointestinal

tract and in an active manner in the kidney. It is subjected to

intestinal secretion and reabsorption via enterohepatic recycling.

Binding of OA in the blood to the albumin fraction and recycling in

the bile and kidney contributes to its long half-life in animals.

Ochratoxin A is hydrolyzed to its nontoxic alpha form (O alpha) by

microorganisms in the rumen, cecum, and large intestine. The toxin is

excreted primarily in the urine as O alpha and to a lesser degree as

OA; smaller amounts of OA and O alpha are generally excreted in the

feces. Three distinct mechanisms of OA toxicity have been proposed;

other toxic effects of OA seem to be secondary in nature. Several

different strategies can be employed for controlling or neutralizing

the effect of OA, including the use of proper storage conditions, the

use of specific adsorbents to reduce absorption of OA, and the feeding

OA-contaminated feedstuffs to ruminants. Antioxidants such as ascorbic

acid have been shown to reduce the toxic effects of OA in laying hens.

In summary, OA contamination of cereal food and feed may occur, given

appropriate conditions. Implementation of suitable procedures may

eliminate or minimize this potentially serious problem.

Publication Types:

* Research Support, Non-U.S. Gov't

* Review

PMID: 1474034 [PubMed - indexed for MEDLINE]

Food Chem Toxicol. 1992 Mar;30(3):201-4.

Related Articles, Links

Ochratoxin A in blood and its pharmacokinetic properties.

Fuchs R, Hult K.

Institute for Medical Research and Occupational Health, University

of Zagreb, Croatia.

Since there are pathomorphological similarities between porcine

mycotoxic nephropathy caused by ochratoxin A and Balkan endemic

nephropathy (BEN), it has been suggested that the same aetiological

agent has a role in BEN. Based on the results from several field and

experimental studies carried out on pigs, an appropriate analytical

method of monitoring possible human exposure to ochratoxin A was

developed. The toxicokinetic properties of the toxin were species

specific, although in all the animal species studied (with the

exception of fish), as well as in humans, two binding proteins were

found in the plasma. The monkey had the longest elimination half-life

of the toxin, 510 hr, in contrast to the fish whose elimination

half-life was only 0.68 hr. The fish kidney displayed a specific

pattern of distribution. In the laying quail the most prominent

observation was the accumulation of labelled ochratoxin A in egg yolk.

Generally, [14C]ochratoxin A was eliminated rapidly from the quail

body, but had a long retention time in the circulating blood in the

mouse. Although the elimination of ochratoxin A from the body

depending on its binding to plasma constituents, the existence of

enterohepatic circulation might have been partially responsible for

its prolonged retention and elimination from the body of mammals. The

toxicokinetic profile of ochratoxin A did not contradict the mycotoxic

hypothesis in the aetiology of BEN.

Publication Types:

* Review

PMID: 1618443 [PubMed - indexed for MEDLINE]

IARC Sci Publ. 1991;(115):187-200.

Related Articles, Links

Pharmacokinetics of ochratoxin A in animals.

Galtier P.

Laboratoire de Pharmacologie-Toxicologie, Institut National de la

Recherche Agronomique, Toulouse, France.

The fate of ochratoxin A has been studied in laboratory rodents

and in breeding animals. In rats, orally administered ochratoxin A is

readily absorbed, and considerable amounts of the toxin are detected

in plasma, where maximal concentrations occur 2-4 h after

administration. Pharmacokinetic analysis of curves of plasma level

versus time suggests its distribution in two distinct body

compartments. The half-time of the toxin depends on both the dose and

the animal species, varying from 0.7 h in fish to 840 h in monkeys. In

plasma, the toxin is bound to albumin, like many acidic compounds.

This interaction is competitively inhibited by phenylbutazone,

ethylbiscoumacetate and sulfamethoxy-pyridazine and is decreased in

albumin-deficient rats. The hydrolysis of ochratoxin A to an

isocoumarin derivative (ochratoxin alpha) is the major metabolic

pathway. This detoxication is brought about by animal and bacterial

carboxypeptidases and takes place in the rumen and large intestine.

4-Hydroxyochratoxin A is the main hepatic metabolite, and its

formation appears to be polymorphic, like debrisoquine

4-hydroxylation. The ratio of 4-hydroxyochratoxin A to ochratoxin A

excreted in urine may be linked to the carcinogenic potential of the

toxin, as the metabolite is almost as effective an immunosuppressor as

ochratoxin A. After undergoing enterohepatic circulation, the toxin

and ochratoxin alpha are excreted in faeces and urine as various

unidentified metabolites. Transport of the mycotoxin in the kidney is

mediated by the renal organic anion transport system, and renal

metabolism may contribute to detoxification. Although dose-dependent

placental transfer of ochratoxin A has been described in rodents, the

toxin does not cross the placenta into fetuses of sows administered a

low dose (0.38 mg/kg) orally. Its diffusion into the milk of female

rabbits is seen after intravenous administration, but in cows given 50

mg of the mycotoxin, barely detectable amounts of ochratoxin alpha

were recovered in milk. Ochratoxin A is preferentially distributed in

liver, kidney, muscle and fat. The experimental data are in close

accordance with several reports on the spontaneous occurrence of

unchanged toxin residues in blood and kidneys of slaughter pigs.

Publication Types:

* Review

PMID: 1820333 [PubMed - indexed for MEDLINE]

J Environ Pathol Toxicol Oncol. 1990 Jan-Apr;10(1-2):56-63.

Related Articles, Links

The mode of action of ochratoxin A in acute enteritis in rats.

Kanisawa M, Suzuki S, Moroi K.

Department of Pathology, Yokohama City University School of Medicine, Japan.

The mode of action of ochratoxin A(OCT A) was studied in male

Wistar rats in connection with the development of acute enteritis.

Acute enteritis in the duodenum and jejunum identical with that

induced by oral administration was also induced by parenteral

application at the dose level of 15 mg/kg OCT A and was completely

inhibited by ligation of the choledochus. Direct application of OCT A

into the jejunal blind sac lumen constructed by two ligations induced

severe inflammation in situ and also revealed remote action to the

duodenum and jejunum where separated from the blind sac by ligation.

This remote action was inhibited by ligation of the choledochus. These

results clearly demonstrated the enterohepatic circulation of OCT A.

The ileal injection also revealed remote action of OCT A, although no

pathologic change was caused in the ileal mucosa. The results obtained

suggest that the enteritis may be induced by direct exposure of OCT A

to the intestinal mucosa without metabolic activation, although

certain participation of ochratoxin alpha to accelerate the

inflammation was suspected.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 2231315 [PubMed - indexed for MEDLINE]

Drug Metab Dispos. 1989 Nov-Dec;17(6):600-5.

Related Articles, Links

Click here to read

Enterohepatic circulation of T-2 toxin metabolites in the rat.

Coddington KA, Swanson SP, Hassan AS, Buck WB.

Department of Veterinary Biosciences, University of Illinois.

The enterohepatic circulation of T-2 toxin and its conjugated

metabolites was examined in bile duct-cannulated male rats. Rats

administered tritiated T-2 toxin intraduodenally (id) eliminated

44.65% and 57.25% of the administered dose in the bile within 4 and 8

hr post-dosing, respectively. TLC profiles of the T-2 metabolites were

similar after intravascular and id administration. The major

metabolites detected were 3'-OH-hydroxytryptamine-2 (HT-2), glucuronic

acid conjugates, T-2 tetraol (TOL), 4-deacetylneosolaniol (4-DN), and

HT-2. Tritium-labeled glucuronides obtained from the bile of rats

administered [3H]T-2 toxin intravascularly were extracted and purified

using C-18 and silica column chromatography. Enzymatic hydrolysis

followed by TLC and GC/MS indicated that the aglycone portion of the

glucuronides were composed of 3'-OH HT-2, HT-2, 4-DN, and TOL. After

id administration of the glucuronides the rats eliminated 6.01% (4 hr)

and 11.86% (8 hr) of the dose in the bile. No free metabolites of T-2

toxin were detected in the bile of any animals administered the

purified glucuronides. Oral treatment of the rats with the

beta-glucuronidase inhibitor, saccharolactone, did not produce a

significant decline in the amount of radioactivity recovered in the

bile following administration of the tritium-labeled glucuronides.

These studies substantiate the enterohepatic circulation of T-2 toxin

metabolites.

Publication Types:

* Research Support, U.S. Gov't, Non-P.H.S.

PMID: 2575494 [PubMed - indexed for MEDLINE]

J Anim Sci. 1988 Jul;66(7):1703-11.

Related Articles, Links

Click here to read

Studies of the tolerance and disposition of ochratoxin A in young calves.

Sreemannarayana O, Frohlich AA, Vitti TG, Marquardt RR, Abramson D.

University of Manitoba, Winnipeg, Canada.

Tolerance to and disposition of ochratoxin A (OA) were compared in

preruminant and ruminant calves. Two preruminant calves receiving 4.0

mg OA/kg body weight by stomach tube died; one of two calves receiving

1.0 mg/kg body weight survived. At a dose of .5 mg OA/kg body weight

both calves survived. The administered OA was converted mainly (80.1

to 88.9%) to ochratoxin-alpha (O alpha), which was found only in

urine; the remaining OA appeared in the urine (3.2 to 3.3%) and feces

(7.8 to 10.0%). In the one surviving calf of two given .25 mg OA/kg

body weight i.v., nearly twice as much OA was excreted in the feces

(44.5%) as in the urine (25.0%); no O alpha was found in urine or

feces. All four calves with functional rumens receiving OA orally, 2.0

mg/kg body weight, survived without overt ill effects. Approximately

90% of the OA was excreted as O alpha, with approximately four to

eight times more in the urine than in the feces; OA was low in the

urine or feces. A plot of the serum OA concentration-time data

revealed a prominent, sustained, secondary peak, which was described

adequately by a four-exponential equation with two apparent absorption

components. Accordingly, OA initially was absorbed rapidly by a

first-order rate process (ka = .496/h), and following a considerable

delay (tlag = 12.84 h) absorption appeared to resume by a second,

slower, first-order rate process (ka = .127/h). The second absorption

phase was best explained as being due to enterohepatic cycling of

OA.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types:

* Comparative Study

* Research Support, Non-U.S. Gov't

PMID: 3403401 [PubMed - indexed for MEDLINE]

Toxicology. 1988 Mar;48(3):293-308.

Related Articles, Links

Evidence for an enterohepatic circulation of ochratoxin A in mice.

Roth A, Chakor K, Creppy EE, Kane A, Roschenthaler R, Dirheimer G.

Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.

The distribution and elimination of [3H]ochratoxin A (OTA) from

stomach content and tissue, intestine content and tissue, liver, bile,

serum and urine of Swiss male mice which had received a single low

dose of OTA by intubation was followed as a function of time. The

profiles of radioactivity do not show a smooth decline after the

absorption period, but an oscillating pattern with rapid declines

followed by increases which favour the assumption of an enterohepatic

circulation. Between 28% and 68% of conjugated OTA together with OTA

cleavage products were found in bile giving evidence for biliary

excretion of OTA and its metabolites in mice. When given i.m. to mice

[3H]OTA is already found after 30 min in bile and intestine contents

and its elimination patterns show several peaks confirming the biliary

excretion and the enterohepatic circulation. Cholestyramine, which is

known to prevent the enterohepatic circulation of drugs and toxins,

changes the profile of elimination of OTA which no longer presents the

cyclic pattern. This result is also in favour of an enterohepatic

circulation of OTA. When phenylalanine is given together with OTA by

oral gavage the toxicokinetics of the mycotoxin change completely in

the different body fluids, in stomach and intestine content and

tissues. Phenylalanine seems to facilitate the gastric absorption of

OTA and the gastro-intestinal transit. It increases also its early

excretion into urine and bile. However, its elimination pattern no

longer shows the oscillating pattern. Thus phenylalanine seems to

inhibit the intestinal reabsorption of OTA conjugates.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 3344528 [PubMed - indexed for MEDLINE]

Vopr Pitan. 1988 Mar-Apr;(2):51-5.

Related Articles, Links

[Effect of qualitatively varying nutrition on several parameters

of aflatoxin B1 metabolism and toxicokinetics]

[Article in Russian]

Nikov PS, Bozhko DM, NeÄ­man LA, Antropova LP.

The influence of qualitatively different nutrition (physiological

and that with lysine, methionine, threonine and vitamins A, B, C

deficiencies) on certain toxicokinetic parameters of 3H-aflatoxin B1,

after single and multiple (every day, during 5 days) intraperitoneal

injections of this agent in a dose of 25 micrograms/animal, was

studied in two series of experiments on growing male WAG rats with the

initial bw 40-50 g. It has been proved that the main parameters of

aflatoxin B1 toxicokinetics depend on the injection multiplicity and

the nutrition character. It has been established that the qualitative

differences in the nutrition character essentially influence the

stages of aflatoxin B1 distribution in the body, the sorption and

metabolic transformation in the liver, enterohepatic recirculation,

the rate and correlation of the main elimination routes. The nutrition

character influences the level of persistence and cumulation of firmly

bound aflatoxin B1 adducts in the liver and hepatocytic DNA. Possible

mechanisms of such effects of different providing of the body with

essential nutrients have been discussed. A conclusion has been made

that the modifying effect of nutrition on the key stages of aflatoxin

B1 toxicokinetics is realized, ultimately, in varying degree of the

animal resistance to mutagenic and carcinogenic action of this agent.

Publication Types:

* Comparative Study

* English Abstract

PMID: 3133878 [PubMed - indexed for MEDLINE]

: Nutr Cancer. 1983;5(1):41-50.

Related Articles, Links

Vitamin A and aflatoxin: effect on liver and colon cancer.

Suphakarn VS, Newberne PM, Goldman M.

A vitamin A (retinyl acetate)-deficient diet enhanced liver cancer

in rats exposed to aflatoxin B1 (AFB1) and also caused a 29% incidence

of colon cancer. The following factors were considered in attempts to

define conditions under which vitamin-A-deprived rats were more

susceptible to colon cancer induced by AFB1: liver morphology,

enterohepatic recirculation, level of reduced glutathione (GSH) in

liver, and differing capacities for conjugation of aflatoxin to GSH.

Enzyme concentrations in liver, in intestinal and colon mucosa, and in

intestinal and colon contents suggested that AFB1 may have different

metabolites and that there may be differing susceptibilities of colon

mucosa to carcinogenesis. Binding studies supported this hypothesis.

Previous studies have shown that colon epithelium from

vitamin-A-deficient rats binds more AFB1 than colon epithelium from

normal, vitamin-A-supplemented animals. In the present study, vitamin

A supplementation to the vitamin-A-deficient rats before oral

administration of 3H-AFB1 significantly decreased the binding capacity

at 12 and 15 hours after dosing with the carcinogen. These results

suggest that the effect of vitamin A on the metabolism of the

carcinogen, particularly on binding of AFB1 to cellular

macromolecules, may be the mechanism by which vitamin A modifies

aflatoxin's carcinogenic potential, influenced in part through

enzymatic mechanisms.

PMID: 6415617 [PubMed - indexed for MEDLINE]

Arzneimittelforschung. 1980;30(3):452-4.

Related Articles, Links

Silybin inhibition of amatoxin uptake in the perfused rat liver.

Faulstich H, Jahn W, Wieland T.

Silybin dihemisuccinate, in a concentration of 0.4 mg/ml, almost

completely inhibited the uptake of an amatoxin by the perfused rat

liver. Similary, silybin should also interrupt absorption of toxins

due to enterohepatic circulation, e.g. in dog and man. This effect may

become important in the therapy of human Amanita poisoning.

Publication Types:

* In Vitro

PMID: 7387753 [PubMed - indexed for MEDLINE]

Naturwissenschaften. 1979 Aug;66(8):410-2.

Related Articles, Links

[Amatoxins and mushroom poisoning]

[Article in German]

Faulstich H.

Amatoxins are the sole cause of human Amanita poisoning,

inhibition of transcription eventually leading to cell necrosis. The

toxins are easily excreted into the bile fluid, a fact which

postulates the interruption of the enterohepatic circulation. All

therapeutic means should be applied in order to decrease the serum

concentration of the toxins as soon as possible.

Publication Types:

* English Abstract

PMID: 503239 [PubMed - indexed for MEDLINE]

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

Ne gardez plus qu'une seule adresse mail ! Copiez vos mails vers