Cardiac allograft vasculopathy (CAV) continues to limit the long-term success of cardiac transplantation. Recent insights have underscored the fact that innate and adaptive immune responses are involved in the pathogenesis of CAV. Vascular lesions are the result of cumulative endothelial injuries induced both by alloimmune responses and by nonspecific insults (including ischemia-reperfusion injury, viral infections, and metabolic disorders) in the context of impaired repair mechanisms. Intravascular ultrasound is the most sensitive method for detection of CAV, and progressive intimal thickening in the first posttransplant year identifies patients at high risk for future cardiovascular events. Encouraging results with regard to the detection of CAV by noninvasive methods should be an incentive to apply routine noninvasive imaging during mid- to long-term follow-up. Improved immunosuppressive drugs, including mycophenolate mofetil and proliferation signal inhibitors, as well as statins (in part via immunomodulation), have beneficial effects on CAV progression, although there is still a need to confirm the impact of vasodilators in improving outcome after heart transplantation. Coronary revascularization for CAV is only palliative, with no long-term survival benefit. Three main strategies for CAV prevention are currently under investigation: inhibition of growth factors and cytokines, cell therapy, and tolerance induction. However, because individual responses to an allograft change over time, assays to monitor the recipient's immune response and individualized methods for therapeutic immune modulation are clearly needed.

Cardiac Allograft Vasculopathy : Recent Developments

Oxidative stress is involved in the development of many chronic diseases. One of the main factors involved in oxidative stress reduction is increased antioxidant potential. Some nutrients such as vitamin C, vitamin E and carotenoids are known to act as antioxidants; however, riboflavin is one of the neglected antioxidant nutrients that may have an antioxidant action independently or as a component of the glutathione redox cycle. Herein, studies that have examined the antioxidant properties of riboflavin and its effect on oxidative stress reduction are reviewed. The results of the reviewed studies confirm the antioxidant nature of riboflavin and indicate that this vitamin can protect the body against oxidative stress, especially lipid peroxidation and reperfusion oxidative injury. The mechanisms by which riboflavin protects the body against oxidative stress may be attributed to the glutathione redox cycle and also to other possible mechanisms such as the conversion of reduced riboflavin to the oxidised form.

/pdf/riboflavin-vitamin-b-and-oxidative-stress-a-review-16kh4lhu1m.pdf

Riboflavin (vitamin B₂) and oxidative stress: a review.

There has lately been a renewed interest in Riboflavin owing to insight into its recognition as an essential component of cellular biochemistry. The knowledge of the mechanisms and regulation of intestinal absorption of riboflavin and its health implications has significantly been expanded in recent years. The purpose of this review is to provide an overview of the importance of riboflavin, its absorption and metabolism in health and diseased conditions, its deficiency and its association with various health diseases, and metabolic disorders. Efforts have been made to review the available information in literature on the relationship between riboflavin and various clinical abnormalities. The role of riboflavin has also been dealt in the prevention of a wide array of health diseases like migraine, anemia, cancer, hyperglycemia, hypertension, diabetes mellitus, and oxidative stress directly or indirectly. The riboflavin deficiency has profound effect on iron absorption, metabolism of tryptophan, mitochondrial dysfunction, gastrointestinal tract, brain dysfunction, and metabolism of other vitamins as well as is associated with skin disorders. Toxicological and photosensitizing properties of riboflavin make it suitable for biological use, such as virus inactivation, excellent photosensitizer, and promising adjuvant in chemo radiotherapy in cancer treatment. A number of recent studies have indicated and highlighted the cellular processes and biological effects associated with riboflavin supplementation in metabolic diseases. Overall, a deeper understanding of these emerging roles of riboflavin intake is essential to design better therapies for future.

Riboflavin and health: A review of recent human research

Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.

/pdf/riboflavin-the-health-benefits-of-a-forgotten-natural-1b17nukryz.pdf

Riboflavin: The Health Benefits of a Forgotten Natural Vitamin

Lycium barbarum has been used in China for more than 2,000 years as a traditional medicinal herb and food supplement. Lycium barbarum contains abundant Lycium barbarum polysaccharides (LBPs), betaine, phenolics, carotenoids (zeaxanthin and β-carotene), cerebroside, 2-O-β-d-glucopyranosyl-l-ascorbic acid (AA-2βG), β-sitosterol, flavonoids and vitamins (in particular, riboflavin, thiamine, and ascorbic acid). LBPs are the primary active components of Lycium barbarum. In this review, we discuss the pharmacological activities of LBPs and other major components. They have been reported to mediate significant anti-aging effects, through antioxidant, immunoregulative, anti-apoptotic activities and reducing DNA damage. Thus, the basic scientific evidence for anti-aging effects of LBPs is already available. However, additional studies are needed to understand mechanisms by which LBPs mediate anti-aging properties. Novel findings from such studies would likely pave the way for the clinical application of traditional chinese medicine Lycium barbarum in modern evidence-based medicine.

Lycium Barbarum: A Traditional Chinese Herb and A Promising Anti-Aging Agent.

Background Riboflavin is a well-known nutritional supplement that has been shown to exhibit antioxidant properties and protect tissue from oxidative damage. We hypothesized that riboflavin given during cardiac ischemia-reperfusion (I/R) might reduce subsequent acute rejection, after allotransplantation, and coronary allograft vasculopathy (CAV). Methods A murine heterotopic cardiac transplantation model was used to test whether riboflavin improves I/R injury and acute/chronic rejection. Results Riboflavin significantly reduced oxidant production and inflammatory mediator production induced by I/R injury, as evidenced by decreased levels of malondialdehyde, myeloperoxidase activity, and tumor necrosis factor alpha. Administration of riboflavin also improved graft survival and suppressed T-cell infiltration and donor-reactive alloantibody formation during the early period after allotransplantation. A murine long-term cardiac allograft model using immunosuppression (preoperative anti-murine CD4 and anti-CD8) was employed to investigate the effect of riboflavin against CAV at 60 days. Riboflavin-treated grafts exhibited a significant decrease in the severity of coronary artery luminal occlusion as compared with saline-treated grafts (17.4+/-1.8% vs. 43.5+/-5.6%, P=0.0012). However, there was no significant effect of riboflavin to reduce donor-reactive alloantibodies in this chronic model. Conclusions These data indicate that riboflavin improves early I/R injury and reduces the development of CAV, most likely due to alloantigen-independent effects such as reduced early graft oxidant stress. Riboflavin administered in the setting of cardiac allograft transplantation appears to be a powerful means to reduce early graft lipid peroxidation, leukocytic infiltration, and cytokine production as well as to suppress the late development of cardiac allograft vasculopathy.

Riboflavin-mediated reduction of oxidant injury, rejection, and vasculopathy after cardiac allotransplantation.

Oxidant injury occurs when an organ is severed from its native blood supply and then reperfused and continues during subsequent periods of immune attack. Experiments here test the hypothesis that an antioxidant given only in the peri-reperfusion period protects against not only oxidative but also nitrosative stress, leading to reduced vasculopathy long after cardiac allotransplantation. Experiments were performed using a murine heterotopic cardiac transplantation model. An antioxidant, in the form of intraperitoneal high-dose riboflavin, was given to recipients during the initial 3 days after transplantation. Antioxidant-treated mice showed significantly longer graft survival than control mice. At 4 h after transplantation, antioxidant treatment significantly reduced graft lipid peroxidation and oxidized DNA and preserved antioxidant enzyme activity. At day 6 posttransplantation, the redox-sensitive transcription factor nuclear factor-κB and inducible nitric oxide synthase were significantly reduced following antioxidant treatment, with concomitant reduction of nitrotyrosine. Despite the limited duration of antioxidant treatment, both acute and chronic rejection were significantly suppressed. In vitro experiments confirmed suppression of nitrosative and oxidative stress and cardiomyocyte damage in antioxidant-treated cardiac allografts. Collectively, antioxidant administration during the initial 3 days after transplantation significantly reduces nitrosative and oxidative stress in cardiac allografts, modulates immune responses, and protects against vasculopathy.

Suppression of nitrosative and oxidative stress to reduce cardiac allograft vasculopathy

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Riboflavin-mediated reduction of oxidant injury, rejection, and vasculopathy after cardiac allotransplantation.

Suppression of nitrosative and oxidative stress to reduce cardiac allograft vasculopathy