Message Number: SG17708 | New FHL Archives Search
From: sukiec@optonline.net
Date: 2006-06-28 17:16:40 UTC
Subject: [ferrethealth] RE: BHA, BHT, Ethoxyquin and Propyl Gallate
To: ferrethealth@smartgroups.com

Often when a site villainizes an item like a preservative there is a tenden=
cy to cite false references or old ones, and often to put up part of what w=
as found rather than the full picture.

In relation to at least one of the preservatives recently being again attac=
ked on non-expert websites the most recent references I could find cited on=
two of the those websites was almost 20 years old. You can find more rece=
nt things or just as recent things by searching the preservative name and D=
VM in the FML archives (but read the signature lines to see who is a DVM an=
d who isn't). I still have to look at the FHL archives so you will want to=
do that yourself.

Remember why preservatives are used. They stop growths which are by themse=
lves dangerous (infection, organ damage, death is severe enough, and some c=
an set the stage for malignancies). By stopping growths they also prevent =
the dangerous products some growths create (poisoning, organ damage, induce=
d insanity for some of the toxins, death is severe enough, and some of the =
toxins set the stage for malignancies).

Have some preservatives been associated with increased rates of some specif=
ic malignancies in NON-ferret animals when given in huge amounts? Yes. Ha=
ve at least some of the SAME preservatives been associated with reduced (ye=
s, reduced) rates of other malignancies in those same studies and others? =
Yes. Do the preservatives themselves help prevent malignancies through the=
ir preservation effect? Yes.

Is it always safe to generalize from rodent studies to ferret health? No, =
not by a long shot.

Did the early studies compare risk factors from the growths that arise when=
preservatives are not present compared to risk factors from the preservati=
ves? Some may have done so, but if so I haven't found such ones form then,=
yet. The more complete info came later.

Have any of the preservatives talked about on various sites recently been f=
ormally studied in ferrets? Try looking up the compound along with the wor=
d
ferret
or the word
mustela
in places like Pubmed.

The closest you will find is a study on carotinoids (You know, the compound=
in carrots) so it was probably just mentioned as the preservative but i do=
n't have the article itself.

START QUOTE

Methods Enzymol. 1993;214:102-16.
Related Articles, Links

Analysis of carotenoids in human and animal tissues.

Schmitz HH, Poor CL, Gugger ET, Erdman JW Jr.

Department of Food Science, North Carolina State University, Raleigh 27695.=


PMID: 8469135 [PubMed - indexed for MEDLINE]

END QUOTE


(the only study involving ferrets and BHT, Butylated Hydroxytoluene found)

None for ferrets and BHA, Butylated Hydroxyanisole.

None for ferrets and ethoxyquin.

None for Propyl Gallate and ferret

This gets across well that some of the natural preservatives and some of th=
e human-created ones are "double edged swords":

START QUOTE

Antioxid Redox Signal. 2005 Nov-Dec;7(11-12):1728-39.


Evaluation for safety of antioxidant chemopreventive agents.

Kawanishi S, Oikawa S, Murata M.

Department of Environmental and Molecular Medicine, Mie University Graduate=
School of Medicine, Mie, 514-8507, Japan. kawanisi@doc.medic.mie-u.ac.jp

Antioxidants are considered as the most promising chemopreventive agents ag=
ainst various human cancers. However, some antioxidants play paradoxical ro=
les, acting as "double-edged sword." A primary property of effective and ac=
ceptable chemopreventive agents should be freedom from toxic effects in hea=
lthy population. Miscarriage of the intervention by beta-carotene made us r=
ealize the necessity for evaluation of safety before recommending use of an=
tioxidant supplements for chemoprevention. We have evaluated the safety of =
antioxidants on the basis of reactivity with DNA. Our results revealed that=
phytic acid, luteolin, and retinoic acid did not cause DNA damage under th=
e experimental condition. Furthermore, phytic acid inhibited the formation =
of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an indicator of oxidative DNA damag=
e, in cultured cells treated with a H(2)O(2)-generating system. Thus, it is=
expected that these chemopreventive agents can safely protect humans again=
st cancer. On the other hand, some chemopreventive agents with prooxidant p=
roperties (alpha-tocopherol, quercetin, catechins, isothiocyanates, N-acety=
lcysteine) caused DNA damage via generation of reactive oxygen species in t=
he presence of metal ions and endogenous reductants under some circumstance=
s. Furthermore, other chemopreventive agents (beta-carotene, genistein, dai=
dzein, propyl gallate, curcumin) exerted prooxidant properties after metabo=
lic activation. Therefore, further studies on safety should be required whe=
n antioxidants are used for cancer prevention. Antioxid. Redox Signal. 7, 1=
728-1739.

Publication Types:
Review

PMID: 16356133 [PubMed - indexed for MEDLINE]

END QUOTE

There are studies for preservatives mentioned which make a person notice th=
at while some types of malignancies may have their rates increased by the p=
reservative use others have their rates decreased. So, it becomes importan=
t to notice specifically which preservatives are being discussed and which =
specific malignancies are being discussed and then think (among other thing=
s) about which types ferrets are more inclined to get.

Pubmed is a GREAT resource. I just wish that I was more able to comprehend=
some of the abstracts well enough, especially the most recent ones which c=
arry the more useful data often.

I THINK (but am NOT well enough educated in the right things to know for su=
re) that each of the below shows at least a bit of the other side of the st=
ory, situations in which some risks may be reduced, at least in part. Then=
again, I could be falling flat on my face (SPLAT!) in my insufficiently we=
ll education take on what I am reading:

The most recent study (2002) from Nagoya involving Butylated Hydroxytoluene=
and if I read it right it had the oil BHT helped preserve decrease UVB inj=
ury to skin in mice.

START QUOTE

Photochem Photobiol. 2002 Dec;76(6):657-63.


Dietary, but not topical, alpha-linolenic acid suppresses UVB-induced skin =
injury in hairless mice when compared with linoleic acids.

Takemura N, Takahashi K, Tanaka H, Ihara Y, Ikemoto A, Fujii Y, Okuyama H.

Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuhok=
u, Nagoya, Japan.

Peroxidizability of fatty acids in the air is roughly proportional to the n=
umber of double bonds, but in vivo peroxidation proceeds in a more complex =
manner. Here, we compared the effects of dietary and topically applied oils=
enriched with linoleic acid (LA, 18:2n-6) or alpha-linolenic acid (ALA, 18=
:3n-3) on UV-induced skin injury in a strain of hairless mice. The UVB-indu=
ced erythema score was significantly lower in mice with topically applied c=
reams containing LA and ALA than in mice with the basal cream; no significa=
nt increase in the score was detected in the ALA group compared with the LA=
group. However, dietary ALA inhibited the increase in erythema score after=
UVB irradiation compared with LA. The peroxidizability index of the skin t=
otal lipids was significantly higher, but UVB-induced prostaglandin E2 (PGE=
2) production was significantly lower in the group fed an ALA-rich diet com=
pared with the group fed an LA-rich diet. The levels of thiobarbituric acid=
-reactive substances, estimated in the presence of butylated hydroxytoluene=
in the assay mixture, were not affected by UVB treatment or by the dietary=
fatty acids, but the severity of the skin lesion was associated with PGE2 =
levels. These results indicate that the type of fatty acids, n-6 or n-3, is=
critical for the suppression of UVB-induced skin lesion when the skin fatt=
y acids are modified by dietary manipulation. Anti-inflammatory activity of=
dietary flaxseed oil with relatively high ALA and low LA contents was demo=
nstrated in UVB-irradiated hairless mice.

PMID: 12511046 [PubMed - indexed for MEDLINE]

END QUOTE

The most recent study from that university (referred to on one of the "pres=
ervatives are the devil's work" sites on Butylated Hydroxyanisole was in ra=
ts and was in 1999.

START QUOTE

Food Chem Toxicol. 1999 Sep-Oct;37(9-10):985-92.
Related Articles, Links

?
Phenolics: blocking agents for heterocyclic amine-induced carcinogenesis.

Hirose M, Takahashi S, Ogawa K, Futakuchi M, Shirai T.

First Department of Pathology, Nagoya City University, Medical School, Nago=
ya, Japan.

Chemopreventive effects of synthetic and naturally occurring antioxidants o=
n heterocyclic amine (HCA)-induced rat carcinogenesis and mechanisms of inh=
ibition were assessed. In a medium-term liver bioassay, combined treatment =
with 0.03% 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and synthe=
tic antioxidants such as 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), buty=
lated hydroxyanisole (BHA), butylated hydroxutoluene (BHT), tert-butylhydro=
quinone (TBHQ) or propyl gallate, each at a dose of 0.25%, inhibited develo=
pment of preneoplastic glutathione S-transferase placental form (GST-P) pos=
itive foci as compared with MeIQx alone, after initiation with diethylnitro=
samine (DEN). Of these antioxidants, HTHQ showed the greatest activity. 8-H=
ydroxydeoxyguanosine (8-OHdG), a marker for DNA damage induced by active ox=
ygen species, and malonedialdehyde and 4-hydroxynonenal levels were not lar=
gely influenced by the treatment with MeIQx or antioxidants, either alone o=
r in combination. In the same medium-term liver bioassay, effects of some n=
aturally occurring antioxidants, such as green tea catechins (GTC), hesperi=
din, chlorogenic acid, quercetin, rutin, curcumin, daidzin, ferulic acid an=
d genistein were also examined. Of these antioxidants, only GTC tended to i=
nhibit GST-P positive foci development, while quercetin, rutin, curcumin, d=
aidzin, ferulic acid and genistein all exerted significant enhancing effect=
s. Examination of HTHQ influence in a medium term liver bioassay with HCA G=
lu-P-1, in which the experimental period was extended for up to 26 weeks, a=
lso demonstrated a significant decrease in the incidence of liver tumours t=
o 40% in the group treated with 0.5% HTHQ and 0.03% 2-amino-6-methyldipyrid=
o[1,2-a:3',2'-d]imidazole (Glu-P-1) as compared with the Glu-P-1 alone valu=
e of 89%. Effects of HTHQ on colon carcinogenesis induced by 2-amino-1-meth=
yl-6-phenylimidazo[4,5-b]pyridine (PhIP) were evaluated in a two-stage colo=
n carcinogenesis model using 1,2-dimethylhydrazine (DMH) as an initiator. A=
t week 36, the multiplicity of colon tumours induced by 0.02% PhIP after DM=
H initiation (9.1+/-6.2/rat) was dose-dependently decreased by the combined=
treatment with 0.5% HTHQ (3.6+/-1.8, P < 0.001) and 0.125% HTHQ (6.2+/-3.2=
, not significant). Similarly, the incidence of mammary carcinomas in femal=
e F344 rats induced by oral administration of 0.02% PhIP (40%) for 52 weeks=
was significantly decreased by simultaneous treatment with 0.5% HTHQ (5%).=
Alpha-tocopherol and chlorophyllin only reduced the multiplicity of carcin=
omas. Analysis of the influence of HTHQ on metabolic activation of Glu-P-1 =
or PhIP after incubation with rat S9 mixture and NADPH by HPLC, revealed th=
at each major metabolite was strongly reduced by the addition of HTHQ. Immu=
nohistochemically detected PhIP-DNA adduct positive nuclei in the colon ind=
uced by continuous oral treatment with 0.02% PhIP for 2 weeks decreased by =
the combined treatment with 0.5 or 0.125% HTHQ. These results indicate that=
synthetic antioxidant HTHQ is a very strong chemopreventor of heterocyclic=
amine (HCA)-induced carcinogenesis and that depressed metabolic activation=
rather than antioxidant activity is responsible for the observed effect.

PMID: 10541455 [PubMed - indexed for MEDLINE]

END QUOTE

START QUOTE

Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):514-9. Epub 2005 Dec 15.


Elevated concentrations of nonesterified fatty acids increase monocyte expr=
ession of CD11b and adhesion to endothelial cells.

Zhang WY, Schwartz E, Wang Y, Attrep J, Li Z, Reaven P.

Department of Medicine, Carl T. Hayden Veterans Affairs Medical Center, Pho=
enix, AZ 85012, USA. weiyang.zhang@med.va.gov

OBJECTIVE: Monocyte proinflammatory activity has been demonstrated in obesi=
ty, insulin resistance, and type 2 diabetes, metabolic conditions that are =
frequently associated with elevated levels of nonesterified fatty acids (NE=
FA). We therefore tested the hypothesis that NEFA may induce monocyte infla=
mmation. METHODS AND RESULTS: Monocytes exposed to NEFA for 2 days demonstr=
ated a dose-related increase in intracellular reactive oxygen species (ROS)=
formation and adhesion to endothelial cells. All of these effects were inh=
ibited by the coaddition of antioxidants such as glutathione or butylated h=
ydroxytoluene, by inhibition of ROS generation by NADPH oxidase inhibitors,=
and by inhibition of protein kinase C, a recognized stimulator of NAPDH ox=
idase. Monocytes exposed to NEFA also demonstrated a significant increase i=
n CD11b message expression. Stimulation of monocyte adhesion to endothelial=
cells by NEFA was inhibited by addition of neutralizing antibodies to eith=
er CD11b or CD18. Finally, surface expression of CD11b increased significan=
tly on monocytes as measured by flow cytometry, after their incubation with=
NEFA. CONCLUSIONS: These studies indicate that elevated concentrations of =
NEFA may enhance integrin facilitated monocyte adhesion to endothelial cell=
s and these effects appear mediated, in part, through activation of NADPH o=
xidase and oxidative stress.

PMID: 16357311 [PubMed - indexed for MEDLINE]

END QUOTE

So, to me it looks like there is a mixed picture, but we can't forget that =
not using preservatives can in many ways be more risky than using them, and=
that there is a pretty thoroughly complete lack of ferret-specific data, a=
nd in the locations where people worry the most there is a tendency to to h=
ave old data, incomplete data, and to not separate out the risks according =
to which ones ferrets are more prone to encountering.

So hopefully I didn't fall on my face too badly or too often in this post, =
and hopefully more knowledgeable list members will be able to say more and =
do a far better job of it with more hard data and a better grasp of it than=
I can provide.

-- Sukie (not a vet, and not speaking for any of the below in my private po=
sts)
Recommended health resources to help ferrets and the people who love them:
Ferret Health List
http://www.smartgroups.com/groups/ferrethealth
FHL Archives
http://ferrethealth.org/archive/
AFIP Ferret Pathology
http://www.afip.org/ferrets/index.html
Miamiferrets
http://www.miamiferret.org/fhc/
International Ferret Congress Critical References
http://www.ferretcongress.org
=

=




=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D<<<
Orange Broadband click below:
http://ads.smartgroups.com/adclick/CID=3D000000b7c79a99a500000000
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D>>>
--
If you want to share pictures, use the calendar, or start a vote
visit http://www.smartgroups.com/groups/ferrethealth

To leave the group, email: ferrethealth-unsubscribe@smartgroups.com

Report abuse http://www.smartgroups.com/text/abusereport.cfm?gid%3D1423922&mid%3D17708