The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile
Daria BrambillaCesare MancusoMaria Grazia ScuderiPaolo BoscoGiuseppina CantarellaLaurence LempereurGiulia Di BenedettoSalvatore PezzinoRenato Bernardini
152
Citation
133
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS) play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects.Keywords:
Cancer Prevention
Heme oxygenase, the rate-limiting enzyme in the degradation of heme to bile-pigments and carbon monoxide, is induced in response to increased oxidative stress and is believed to provide a cytoprotective effect. We investigated the role of heme oxygenase in cultured rabbit corneal epithelial cells (RCE), and its potential to alleviate oxidative stress-induced cell damage. Heme oxygenase in RCE was effectively and potently induced by most metals tested, including tin, silver, and gold, and cytokines such as IL-6, and TGFβ. Stannous chloride and heme-induced heme oxygenase mRNA by 40 and 100 fold within 1-3 hours and increased enzyme activity by 9.2- and 10-fold, respectively, over a 24 hour period. IL-6, TGFβ and H2O2 induced heme oxygenase by 2-3 fold. Zinc protoporphyrins were effective inhibitors of heme oxygenase activity in vitro. However, when incubated with cells for 24 h they induced heme oxygenase mRNA but decreased or had no effect on its activity.
Cite
Citations (31)
To explore the involvement of nitric oxide (NO) in the induction of heme oxygenase-1, an essential enzyme in heme catabolism, we studied the effects of NO donors on the expression of heme oxygenase-1 mRNA in HeLa human cervical cancer cells. Treatment with each of three NO donors, sodium nitroprusside, 3-morpholinosydnonimine, and S-nitroso-L-glutathione, caused noticeable increases in the expression levels of heme oxygenase- mRNA, but not heme oxygenase-2 mRNA. On the other hand, nitrite or 8-bromo cGMP exerted no noticeable effect on the levels of heme oxygenase-1 mRNA. We showed that sodium nitroprusside also increased the levels of heme oxygenase-1 protein. The sodium nitroprusside-mediated increase in heme oxygenase-1 mRNA levels was abolished by treatment with actinomycin D. The expression levels of heme oxygenase-1 mRNA were also increased by NO donors in human melanoma and neuroblastoma cell lines. Thus, the observed induction of heme oxygenase-1 may represent an important response to NO or NO-related oxidative stress. The half lives of heme oxygenase-1 and heme oxygenase-2 mRNAs were estimated to be about 3.2 h and more than 5 h, respectively.
Sodium nitroprusside
Biliverdin
Cite
Citations (47)
Cite
Citations (34)
Abstract: Heme oxygenase is an essential enzyme in the heme catabolism that produces carbon monoxide (CO). This study was designed to examine the expression of two heme oxygenase isozyme mRNAs in the human brain and to explore the involvement of nitric oxide (NO) and various neuropeptides in the regulation of their expression. Northern blot analysis showed the expression of heme oxygenase‐1 and heme oxygenase‐2 mRNAs in every region of the brain examined, with the highest levels found in the frontal cortex, temporal cortex, occipital cortex, and hypothalamus. In a human glioblastoma cell line, T98G, treatment with any of three types of NO donors—sodium nitroprusside, 3‐morpholinosydnonimine, and S ‐nitroso‐ l ‐glutathione—caused a significant increase in the levels of heme oxygenase‐1 mRNA but not in the levels of heme oxygenase‐2 and heat‐shock protein 70 mRNAs. Sodium nitroprusside increased the levels of heme oxygenase‐1 protein but not the levels of heat‐shock protein 70 in T98G cells. The increase in content of heme oxygenase‐1 mRNA caused by sodium nitroprusside was completely abolished by the treatment with actinomycin D. On the other hand, the levels of heme oxygenase isozyme mRNAs were not noticeably changed in T98G cells following the treatment with 8‐bromo cyclic GMP, sodium nitrite, or various neuropeptides, such as calcitonin gene‐related peptide, endothelin‐1, and corticotropin‐releasing hormone. The present study has shown the expression profiles of heme oxygenase‐1 and ‐2 mRNAs in the human brain and the induction of heme oxygenase‐1 mRNA caused by NO donors in T98G cells. These findings raise a possibility that the CO/heme oxygenase system may function in concert with the NO/NO synthase system in the brain.
Sodium nitroprusside
Biliverdin
Cite
Citations (97)
COPP
Phorbol
Cite
Citations (29)
Biliverdin
Biliverdin reductase
Cite
Citations (68)
Abstract: To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP. Similarly, expression of heme oxygenases was followed in skin from vitiligo patients before and after PUVA treatment. Single and double immunostainings were used in combination with light and confocal microscopic analysis and Western blotting. Melanocyte expression of heme oxygenase 1 is upregulated, whereas heme oxygenase 2 is reduced in response to UV and 4-TBP. Upregulation of inducible heme oxygenase 1 was also observed in UV-treated explant cultures, in skin of successfully PUVA-treated patients and in melanocytes cultured from vitiligo non-lesional skin. Heme oxygenase encoding genes were subsequently cloned to study consequences of either gene product on cell viability, demonstrating that HO-1 but not HO-2 overexpression offers protection from stress-induced cell death in MTT assays. HO-1 expression by melanocytes may contribute to beneficial effects of UV treatment for vitiligo patients.
Vitiligo
Melanocyte
Depigmentation
Viability assay
Cite
Citations (17)
Generation of reactive oxygen species (ROS) is a normal process. Under physiological conditions, these deleterious species are mostly removed by the cellular antioxidant systems, which include antioxidant vitamins, protein and non-protein thiols, and antioxidant enzymes. An acute bout of exercise at sufficient intensity has been shown to stimulate activities of antioxidant enzymes. This could be considered as a defensive mechanism of the cell under oxidative stress. However, we still have insufficient knowledge about the interaction between exercise and antioxidants, which are important in assessing the adequacy of protection against oxidative damage and about the necessity of dietary manipulation and/or supplementation. This review concerns effects of acute exercise on various oxidative stress parameters and antioxidant defense system.
Cite
Citations (83)
Excitotoxicity
Biliverdin
Knockout mouse
Cite
Citations (83)
The antioxidant activity of rosemary antioxidant compared with BHT antioxidant on snake oil and grape seed oil was discussed in this paper,UV / VIS spectra of rosemary antioxidant was investigated in this paper.The results showed that rosemary antioxidant had the best antioxidant activity,when its concentration was between 0.04% to 0.05%.The oxidation resistance decrease with the increase of the amount.When the amount rose to some degree,it turned out to be catalytic oxidation.The rosemary antioxidant had great absorption at the UVA band,which could improve the protection of UVA in Sunscreen cosmetic.
Cite
Citations (1)