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Prophylactic action of linseed oil against cyclophosphamid damage

A.L. Bhatia | 09.01.2006 15:20 | Health | Birmingham | World

Oral administration of linseed oil (0.1ml/kg b.w. /day) for 20 days prior to an acute dose of cyclophosphamide (75mg/kg) significantly prevented the cyclophosphamide- induced decline in the level of GSH, GSH-Px, alkaline phosphatase in mice blood. The increased activity of acid phosphatase and GSSG was significantly inhibited in linseed oil pre-treated group. Results indicate the prophylactic action of linseed oil against cyclophosphamide-induced oxidative stress.

Linseed or flax (Linum usitatissimum) is a herbaceous annual plant of Lineaceae family. It is an important oilseed and fiber crop. The oil is edible and also due to its quick drying property is used for the preparation of paints, varnishes, printing ink, oil cloth, soap, patent leather and water proof fabrics. In the ayurvedic system of medicine, the seeds of linseed have been used in treatment of biliousness, backache, inflammations, ulcers, urinary discharges, eye troubles, leprosy and epilepsy. According to Unani system of medicine, seeds are mucilaginous, diuretic, aphrodisiac, galactagogue, emmenagogue, and useful in treatment of cough and kidney troubles. Bark and leaves are good for gonorrhoea. Oil from seeds removes biliousness. It is claimed to be useful in loss of appetite, internal wounds and ringworm [1]. Recent studies indicate that flaxseed is the major source of lignan. Phytoestrogens of the lignan type are widely distributed in plant-derived food items and are believed to protect against hormone-dependent cancer. The richest known dietary source of lignan is flaxseed or linseed. Flaxseed has been reported to contain glycosides of secoisolariciresinol as the major lignan, together with small amounts of matairesinol, isolariciresinol, and pinoresinol. Flaxseed is also a good source of alpha-linolenic acid which is an n-3 fatty acid.
Prasad (1999) in his study on rabbit claimed that secoisolariciresinol isolated from flaxseed reduce hypercholesterolemic atherosclerosis and that this effect was associated with a decrease in serum cholesterol, LDL-C, and lipid peroxidation product and an increase in HDL-C and antioxidant reserve [2]. Flaxseed has been demonstrated to inhibit human breast cancer growth and metastasis and down-regulated expression of insulin-like growth factor and epidermal growth factor receptor [3]. Another study on rat suggested that exposure to flaxseed or its purified lignan during suckling inhibits chemically induced mammary tumorigenesis [4]. Dietary supplementation of flaxseed was also found to inhibit the growth and development of prostate cancer in the transgenic adenocarcinoma mouse prostate model [5].
The study carried out in the Department of Zoology, University of Rajasthan, India demonstrated that oral administration of linseed oil for 20 days has not caused any toxic effect on mice. The values of GSH, GSSG, GSH-Px and Phospatase were significantly not different in oil treated group from normal group. The activities of antioxidant enzymes, GSH-Px and alkaline phosphatase were significantly inhibited following cyclophosphamide exposure. However, the levels of GSSG and acid phosphatase were augmented following drug administration. Linseed treatment lowered the blood GSH levels, as well as GSH-Px and alkaline phosphatase activities in comparison to non-treated group, statistically significant at p<0.001 level. The cyclophosphamide-caused increase in the acid phosphatase activity and GSSG level was significantly (p<0.001) prevented in linseed treated group. A profound decline in GSH/GSSG ratio was reported in cyclophosphamide-treated mice. However, linseed treated group showed near the normal level.
Cyclophosphamide is a commonly used chemotherapeutic drug and well-known mutagen and clastogen. It is an alkylating agent, producing the highly active carbonium ion, which reacts with the extremely electron-rich area of nucleic acids and proteins. Results obtained from this study indicate that the linseed oil renders protection against cyclophosphamide-induced oxidative stress. Oxidative stress refers to the cytotoxic consequence of reactive oxygen byproducts: superoxide anions and hydroxyl radicals which are generated as metabolites of normal and aberrant metabolic processes that utilize molecular oxygen. Oxidative stress cause devastating effect on the functional state of the membrane because it alters membrane fluidity, typically decreasing it and thereby allowing ions such as Ca++ to leak into the cell. Therefore, the preservation of cellular membrane integrity depends on protection or repair mechanism capable of neutralizing oxidative reactions. In present study the inhibition of cyclophosphamide induced depletion of GSH level in the linseed-treated animals suggests that linseed oil may scavenge the free radicals formed during oxidative stress. GSH, with its sulfhydryl group, functions in the maintenance of sulfhydryl groups of other molecules (especially proteins), as a catalyst for disulfide exchange reactions, and in the detoxification of foreign compounds, hydrogen peroxide and free radicals. When GSH acts as a reducing agent, its SH becomes oxidized and forms a disulfide link with other molecules of GSH. GSSG, in turn, can be reduced to GSH by the action of GSSG reductase, in a reaction using NADPH. NADPH is recycled by glucose-6 phosphate dehydrogenase via the pentose phosphate pathway, which is particularly important in red blood cells.
The GSSG/GSH ratio may be a sensitive indicator of oxidative stress. GSH-Px is also the major antioxidative enzyme, which decomposes H2O2 to H2O molecules. By doing so, it reduces the formation of hydroxyl radicals. In present study, the cyclophosphamide-induced inhibition of GSH-Px and decrease in GSH/GSSG ratio is reported in mice blood. However, these are maintained to near the normal level in linseed-pretreated mice.
Present study revealed an increase in serum acid phosphatase activity after cyclophosphamide administration. Acid phosphatase is localized in cellular lysosomes. An enhanced Golgi activity and peroxidation of lysosomal membranes due to cyclophosphamide possibly resulted in the efflux of the enzymes and hence an increase in acid phosphatase levels. In present study, linseed pretreated mice shows near the normal level of GSH and acid phosphatase. In addition, alkaline phosphates activity decreased in cyclophosphamide-treated mice. Alkaline phosphatase plays an important role in maintenance of cellular permeability and acts on monophosphoesters. Damage to cell membrane caused by cyclophosphamide may be the reason for reduced activity of alkaline phosphatase. Alkaline phosphatase activity is also protected significantly in linseed-pretreated mice.
The protection afforded by linseed oil might be due to the antioxidative action of its important constituents, the lignans. Flaxseed contains glycosides of secoisolariciresinol as the major lignan, together with small amounts of matairesinol, isolariciresinol, and pinoresinol. The lignan like secoisolariciresinol and pinoresinol are reported to have strong antioxidant nature [6].
Endoh et al (2002) who demonstrated that flaxseed extract inhibit the carbon tetrachloride -induced decrease in the level of reduced glutathione in rat liver [7]. They have also reported that pretreatment of flaxseed extract protect against carbon tetrachloride-induced elevation of DNA strand breaks in the liver cells.
The present finding that linseed ameliorates the depletion of GSH, GSH-Px and alkaline phosphatase activities and reduces the level of GSSG and acid phosphatase in mice make it a potential preventive agent against oxidative stress.

References
[1] Oudhia P. Alsi (Linum usitatissimum) as medicinal herb in Chhattisgarh, India. 2003;  http://www.celestine-india.com/pankajoudhia
[2] Prasad K. Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation 1999; 99:1355-62.
[3] Chen J, Stavro PM, Thompson LU. Dietary flaxseed inhibits human breast cancer growth and metastasis and downregulates expression of insulin-like growth factor and epidermal growth factor receptor. Nutr Cancer 2002;43:187-92.
[4] Chen J, Tan KP, Ward WE, Thompson LU.Exposure to flaxseed or its purified lignan during suckling inhibits chemically induced rat mammary tumorigenesis. Exp Biol Med 2003; 228: 951-8.
[5] Lin X, Gingrich JR, Bao W, Li J, Haroon ZA, Demark-Wahnefried W. Effect of flaxseed supplementation on prostatic carcinoma in transgenic mice. Urology. 2002; 60:919-24.
[6] Harper A, Kerr DJ, Gescher A, Chipman JK. Antioxidant effects of isoflavonoids and lignans, and protection against DNA oxidation. Free Radic Res 1999;31:149-60.
[7] Endoh D, Okui T, Ozawa S, Yamato O, Kon Y, Arikawa J, Hayashi M. Protective effect of a lignan-containing flaxseed extract against CCl(4)-induced hepatic injury. J Vet Med Sci 2002; 64:761-5


A.L. Bhatia
- e-mail: armbha@gmail.com

Comments

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wonderful for mice...

10.01.2006 14:17

but perhaps you could point to some papers which show how this vivisection can be formally extrapolated to humans? Pharmacovigilance is guesswork for the most part, which is why research like this is essentially worthless. Biomechanicisms differ between species far greater than is generally understood, which is why after 30 years and $200bn spent on the "war on cancer" which has focused on animal models, the 'war' has been a failure in terms of humans - except for those researchers/big pharma who have been nicely lining their pockets.

For more information see www.curedisease.net

Colin Blagmore


LINSEED OIL as antioxidant: is it Science Fraud?

21.04.2006 10:50


LINSEED OIL as antioxidant: is it Science Fraud?

In studies of laboratory animals, flaxseed has shown both estrogen-like and anti-estrogenic effects. Although one small pilot study of breast-feeding women showed no adverse effects in infants whose breast-feeding mothers took flaxseed oil, pregnant and breast-feeding women are not advised to use flaxseed or flaxseed oil. Potentially, the unpredictable estrogenic or anti-estrogenic effects may affect developing fetuses and infants. In addition, the possible effects of flaxseed or flaxseed oil on young children have not been studied, so they are not recommended for children under 12 years of age.
Women with hormone-dependent conditions such as endometriosis, uterine fibroids, or cancers of the breast, ovaries, or uterus should not take flaxseed products due to possible estrogenic effects. Men with prostate cancer should also avoid taking flaxseed products.
Flaxseed can block the esophagus or parts of the intestinal tract. Therefore individuals who have had esophageal or intestinal blockages should not use flaxseed.

Precautions
Flaxseed must be taken with adequate quantities of water (about 8 ounces of water or other liquid for each tablespoon of flaxseed) to prevent gastrointestinal blockages.
 http://www.drugdigest.org/DD/DVH/HerbsCareful/0,3924,552063|Linseed%2Boil,00.html

Some people think that they can get all the benefits of flaxseed by taking flaxseed oil instead of freshly ground seed. With the many flaxseed oils now labeled "high lignan" or "ultra lignan," you might think they're right.

Buyer, Beware!


Some people think that they can get all the benefits of flaxseed by taking flaxseed oil instead of freshly ground seed. With the many flaxseed oils now labeled "high lignan" or "ultra lignan," you might think they're right.

Unfortunately, they are very wrong. A new study from Optimal Research in San Diego, California found that flaxseed oils contain very little of the cancer-fighting lignans found in whole flaxseed - even those claimed to be "high lignan" oils! Lignans are naturally present in the seed's outer shell, not in the refined oils - so freshly ground flaxseed is still the best way to get lignans into your diet.

Why the misleading labels?

Medical studies on both animals and humans have used ground flaxseed as well to successfully tread certain cancers. In response to this and related medical news, several manufacturers of flaxseed oil have begun adding seed particles back in the oils to give them trace of the lignan content found in whole flaxseed, and these companies are subsequently advertising the new products as lignan-rich oils. The miniscule amount of lignans added may turn out to be less than consumers would expect from reading the labels and ads.


Big claims, very little value!



The labels may say that the flaxseed oils are "high lignan," but if you read the fine print, you'll see that these claims are usually with a percentage of "particulates" rather than lignans. Optimal Research Labs researcher and author of the Flaxseed Revolution, Michael Bennit, PharmD. reported that in his study of these so called high lignans oils, "lignans were found only in very small percentages in these particulates, and the particulates weren't found throughout the oils. They were located only in a small layer of sludge stuck to the bottom of the bottles."


TOXIC EFFECTS OF LINSEED OIL

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS
CONTRAINDICATIONS
Women who are pregnant should not use supplemental flaxseed oil or flaxseed because of the theoretical possibility that these lignan-containing substances might induce menstruation.
PRECAUTIONS
Infants, young children, and nursing mothers should avoid supplemental flaxseed oil. Because of possible antithrombotic activity, those with hemophilia and those taking warfarin should be cautious about the use of supplemental flaxseed oil or flaxseed. Flaxseed oil intake should be halted in those having surgical procedures.
ADVERSE REACTIONS
Flaxseed oil may cause mild gastrointestinal symptoms, such as diarrhea.
INTERACTIONS
With Drugs
Interactions may occur between flaxseed oil-ALA and its metabolites and warfarin, aspirin and NSAIDs. Such interactions, if they were to occur, might be manifested by nosebleeds and increased susceptibility to bruising. If this does occur, consideration should be given to lowering or stopping intake.
With Nutritional Supplements
Interactions may occur if flaxseed oil is used with other nutritional supplements, such as fish oils, which have antithrombotic activity.
With Herbs

Interactions may occur between ALA and its metabolites with such herbs as garlic (Allium sativa) and ginkgo (Ginkgo biloba). Such interactions might be manifested by nosebleeds and easy bruising.
Potassium Levels
If flaxseed or flaxseed oil is used in high doses or for prolonged periods of time, reduced potassium levels in the body may result. Low potassium levels can result in muscle weakness and potentially dangerous changes in heart rhythm.
LINSEED OIL CAUSE CANCER

See the articles of very high impact-]

Braden LM, Carroll KK. Dietary polyunsaturated fat in relation to mammary carcinogenesis in rats. Lipids 1986;21:285–8.
De Stefani E, Deneo-Pellegrini H, Mendilaharsu M, Ronco A. Essential fatty acids and breast cancer; a case-control study in Uruguay. Int J Cancer 1998;76:491–4.
Bougnoix P. Alpha-linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer. Br J Cancer 1994;70:330–40.
Pandalai PK, Pilat MJ, Yamazaki K, et al. The effects of omega-3 and omega-6 fatty acids on in vitro prostate cancer growth. Anticancer Res 1996;16:815–20.
Giovannucci E, Rimm EB, Colditz GA, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst 1993;85:1571–9.








Andrew De Parg
mail e-mail: pargad@ameinfo.com