Inflammation, Free Radical Damage, Oxidative Stress and Cancer | OMICS International
Relationship between oxidative stress and inflammation has been documented by many authors. Evidences indicated that oxidative stress. Oxidative stress is defined as the imbalance between the generation of microorganisms (inflammation), and (3) radiation, which makes oxidative stress a to establish a firm correlation between these diseases and the role of oxidative . Objective. Cognitive impairment reduces quality of life and is related to vascular and neurodegenerative disorders. However, there is also a.
Total estrogen is usually not measured when a blood test is done with your physical, but definitely should be measured at the same time. Every patient I have ever been involved with, whether human or animal, and even through their own physician or with my own patients, with allergies, autoimmunity and cancer, all had elevated total estrogen.
How does inflammation lead to oxidation, aging, and obesity? | Fats - Sharecare
Many of the human male patients with cancer, all had normal estradiol levels and high levels of total estrogen. Many of the females that were postmenopausal and had cancer, were deficient in estradiol, but had elevated total estrogen.
When a woman becomes postmenopausal, and her estradiol levels decrease, often an estrogen supplement may be prescribed.
Most woman are afraid to use an estrogen supplement, for good reason. A female patient, taking an estrogen supplement, without first measuring her total estrogen, may be inviting disaster, with the end result being cancer. This also includes menstruating women, who are taking birth control pills that contain estrogen.
If it turns out that your total estrogen still remains normal after taking a birth control pill, it is because the progesterone that is included with the estrogen contained in the same birth control pill is being converted into prednisolone, which helps reduce the pituitary hormone stimulation of the inner layer adrenal cortex, and helps reduce the production of adrenal estrogen.
For further information, please read Total Estrogen - Part 1 and Part 2. It should not make a difference to a health care professional whether the problem comes from oxidation, free radicals or inflammation and which came first.
The only concern the health care professional should have, is how to best treat the patient. Often multiple medical disciplines will need to be applied from evidence-based medicine, to alternative, integrative and complimentary medicine. There needs to be respect between the various medical disciplines, so that the best treatment protocol can be attained for the patient.
I hope this article has provided you with helpful information that you can use to help both you and your pet, live a longer, happier and healthier life. There are no simple relations between quantity of polyphenol and its bioavailability in human diet. Most polyphenols are present in the form of esters [ 41 ].
Polyphenols are poorly absorbed from intestine; polyphenols are firstly hydrolyzed by intestinal enzymes or by colonic microflora and then are absorbed. After being modified in different metabolic pathways, they finally come in the blood but not in the initial biological form [ 41 ]. Due to its incomplete absorption, polyphenols may reach the colon, where they are metabolized by the intestinal microbiota giving rise to several bacterial metabolites.
Micromolar amounts of flavonoids and monophenols are recovered in the feces [ 42 ].
Polyphenols on Oxidative Stress 4. Antioxidant Properties of Polyphenols The excessive production of ROS may cause tissue injury that may lead to the inflammatory process [ 43 ]. Polyphenol antioxidant activity depends on the structure of their functional groups.
The number of hydroxyl groups greatly influences several mechanisms of antioxidant activity such as scavenging radicals and metal ion chelation ability [ 44 ]. Polyphenol antioxidant activities are related to their capacity to scavenge a wide range of ROS. Indeed, the mechanisms involved in the antioxidant capacity of polyphenols include suppression of ROS formation by either inhibition of enzymes involved in their production, scavenging of ROS, or upregulation or protection of antioxidant defenses [ 45 ].
Polyphenols may reduce the catalytic activity of enzymes involved in ROS generation. Polyphenols are able to protect against oxidative damage through various mechanisms [ 46 ]. ROS formation has been reported to enhance free metal ions by reduction of hydrogen peroxidase with generation of the highly reactive hydroxyl radical. Lower redox potentials of the polyphenols are thermodynamically able to reduce highly oxidizing free radicals because of their capacity to chelate metal ions irons, copper, etc.From the wings to center stage: How inflammation triggers a multitude of diseases - Longwood Seminar
For instance, quercetin has iron chelating and iron-stabilizing properties. Interaction of Free Radicals with Polyphenols Polyphenols may react in plasma membrane with nonpolar compounds present in the hydrophobic inner membrane layer; such changes in the membrane may affect oxidation rate of lipid or proteins.
Some flavonoids in the hydrophobic core of membrane may prevent access of oxidants and protect the structure and function of membrane [ 48 ]. These processes may help to understand the basic mechanisms of action of polyphenols including cellular interaction and signal transduction. Xanthine oxidase XO is considered as a key source of free radicals, and some flavonoids such as quercetin, silibin, and luteolin have been shown to inhibit such activity. Inhibition of these enzymes reduces the production of AA, prostaglandins, leukotrienes, and NO which are among the key mediators of inflammation.
Arachidonic acid pathway of inflammation is shown in Figure 2. Metabolic pathways involved in arachidonic acid metabolism leading to inflammatory diseases. Bacterial endotoxins and inflammatory cytokines may stimulate macrophages with resulting increased iNOS expression and NO production and subsequent oxidative injury. Polyphenols may inhibit LPS-induced iNOS gene expression and its associated activity in cultured macrophages [ 51 ], thus resulting in decreased oxidative damage.
COX and LOX are the enzymatic activities responsible for the production of metabolites with capacity to increase the oxidative lesion in tissues.
Inflammation, Free Radical Damage, Oxidative Stress and Cancer
Oxidative injury to the tissues may be worsened by metabolites notably those produced in the XO pathway. Deceased oxidative injury has been reported with polyphenols thus reducing the activity of XO [ 53 ].
Polyphenols on Inflammation 5. Modulatory Functions of Polyphenols towards Cells Involved in the Inflammatory Process Anti-inflammatory activities of the polyphenols such as quercetin, rutin, morin, hesperetin, and hesperidin have been reported in acute and chronic inflammation in animal models Table 1.
Rutin is only effective in the chronic inflammatory processes especially in arthritis; and flavanones are also effective in neurogenic inflammation induced by xylene [ 54 ]. Quercetin has been reported to reduce paw edema induced by carrageenan. Anti-inflammatory activities of some polyphenolic compounds.
Polyphenols may affect enzymatic and signaling systems which are involved in the inflammatory processes, such as tyrosine and serine-threonine protein kinases. These enzymes are known to be involved in cell activation processes such as T cell proliferation, B lymphocyte activation [ 56 ], or cytokine production by stimulated monocytes.
Genistein has been reported as a specific inhibitor for tyrosine protein kinase [ 57 ]. This latter compound may be involved in some of anti-inflammatory effects, since T cell proliferation is accompanied by phosphorylation of tyrosine of particular proteins. Polyphenols also exhibit an effect on secretory processes of inflammatory cells.
The Relationship Between Oxidation, Free Radicals and Inflammation - Dr. Alfred Plechner
Indeed, compounds such as luteolin, kaempferol, apigenin, or quercetin have been documented to represent powerful inhibitors of b-glucuronidase and lysozyme released from neutrophils. These polyphenols in addition significantly inhibit arachidonic acid release from cell membranes [ 58 ]. Mechanism of Anti-Inflammatory Effects of Polyphenols Polyphenols may exert anti-inflammatory effects notably through radical scavenging activities, regulation of cellular activities in inflammatory cells, and modulation of the activities of enzymes involved in arachidonic acid metabolism phospholipase A2, COX and arginine metabolism NOSas well as the modulation of the production of other proinflammatory molecules.
Strong evidences are originating from experiments with natural phytochemicals which have been shown to modulate different inflammatory mediators such as metabolites derived from arachidonic acid, various peptides, excitatory amino acids, and cytokines. Polyphenols and Cardiovascular Disease Antioxidant properties of the polyphenols may be beneficial in the process of inflammation and in inflammation induced carcinogenesis [ 6061 ].
Many epidemiological and human studies have proposed that daily intake of polyphenols rich diet such as fruits, vegetables, cocoa, tea, and wine may exhibit fruitful effects in humans [ 6263 ]. Although the active role of flavonoids in connection with CVD needs to be debated, in fact, systematic review on soy and cocoa flavonoids exerts health beneficial effects on preventing the risk of CVD [ 66 ].
The mechanism of polyphenols on vascular function depends on the ability of nitric oxide synthase eNOS and its bioavailability to the endothelium [ 6768 ]. Flavanols and flavonols also can interact and lower the occurrences of age-related vascular injury [ 71 ] with interaction of MAPK signaling [ 72 ] and downregulation of transcription factors i.
Polyphenols and Neurological Diseases The dietary modulation of neurological diseases with polyphenols has been reported widely [ 7475 ]. The protective mechanism of polyphenols on neurodegenerative diseases is to modulate neuronal and glial signaling pathways [ 80 ].
It indicates that there might be a link in signaling pathways and transcription factors and cytokine production in exploring the neuroinflammation response in central nervous system. Furthermore, the ability of polyphenols on neuronal signaling exerts the defense in response to neurotoxicity induced by advanced glycation end products AGEs [ 84 ].
Polyphenols as an Alternative Target for Cancer Therapy The literature revealed that intuitional supplementation of polyphenols decreases the incidences of different forms of cancer [ 85 ]. Polyphenols exert protection against gastrointestinal tract cancers whereas variety of polyphenols in fruits and vegetables are responsible for preventing the incidences of colon cancer [ 86 ].
Oxidative Medicine and Cellular Longevity
Intake of green tea has been suggested to lower the incidences of biliary tract [ 87 ], bladder [ 88 ], breast [ 89 ], and colon cancer, respectively [ 90 ]. Polyphenols may possess anticancer activities by several mechanisms, comprising the elimination of carcinogenic agents [ 91 ], modifying cancer cell signaling [ 92 ] and cell cycle progression [ 93 ], progression of apoptosis [ 94 ], and modulation of enzymatic activities [ 95 ].
Polyphenols have shown antioxidant properties in tea, red wine, and cocoa, fruit, juices, and olive oil which suppresses cancer formation and development [ 96 ], such as interaction with reactive intermediates [ 97 ], and stimulates carcinogenesis and mutagens [ 98 ]. The compounds in green tea especially flavanol, epigallocatechin gallate EGCGpossess anticancer properties via apoptotic induction and prevent cell growth by interference with cell cycle regulatory proteins and signaling proteins which are involved in cell proliferation, transformation, and metastasis [ 92 ].
Conclusion and Perspectives Polyphenols are compounds with various potential biological properties such as antioxidants, anti-inflammatory, antineoplastic, antiaging, cardioprotective, anticancer, and antimicrobial properties. Polyphenols are gaining interest due to their wide applications in different pathological situations.
Oxidative stress activates a variety of inflammatory mediators involved in several chronic diseases. Clinical evidence suggests that oxidative stress and inflammation linked to overproduction of ROS are likely to represent an important component for the development of several diseases including inflammation-associated chronic diseases. Numerous studies performed with animal and cell models suggest that polyphenol dietary intake may be beneficial as adjuvant treatment for the prevention and treatment among such diseases.
However, only few clinical studies, notably those done in a double-blind manner, have been performed in order to establish the relevance of these experimental studies for extrapolation to human beings.