Advances in metal-induced oxidative stress and human disease

Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease

Purpose of reviewZinc is essential for multiple cellular functions including immunity. Many investigators have used zinc supplementation in an attempt to affect the outcome of various diseases. These efforts were aimed at either supporting immunity by zinc administration or correcting the zinc depen

Zinc: role in immunity, oxidative stress and chronic inflammation

The essentiality of zinc was recognized 46 years ago. Zinc deficiency resulting in growth retardation, hypogonadism, immune dysfunction and cognitive impairment affects nearly 2 billion subjects in the developing world. High phytate content of the cereal proteins consumed in the developing world, results in decreased availability of zinc for absorption. Zinc therapy has been very successful and life saving measure in patients with acrodermatitis enteropathica and Wilson's disease. Beneficial therapeutic responses of zinc supplementation have been ovserved in acute diarrhea in children, chronic hepatitis C, shigellosis, leprosy, leishmaniasis, and common cold. Zinc supplementation was effective in decreasing incidences of infection in elderly and patients with sickle cell disease. Zinc supplementation was effective in preventing blindness in 25% of the elderly with dry type of age related macular degeneration. Zinc supplementation in the elderly decreased oxidative stress and decreased generation of inflammatory cytokines. Zinc is an intracellular signaling molecule in monocytes, dendritic cells and macrophages and it plays an important role in cell-mediated immune functions and oxidative stress. Zinc is also an anti-inflammatory agent. These unique properties of zinc may have significant therapeutic benefits in several diseases in humans. In many diseases concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress and increase generation of inflammatory cytokines. Oxidative stress and chronic inflammation may play important causative roles in many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, and auto-immune diseases. It is therefore, important that status of zinc is assessed and zinc deficiency corrected in these chronic diseases. A controlled clinical trial of zinc supplementation in these disorders in order to document the preventive and therapeutic effects of zinc is warranted.

https://josorge.com/publications/Citations/IJL/011.pdf?origin=publication_detail

Impact of the Discovery of Human Zinc Deficiency on Health

It is well-established that the nutritional deficiency or inadequacy can impair immune functions. Growing evidence suggests that for certain nutrients increased intake above currently recommended levels may help optimize immune functions including improving defense function and thus resistance to infection, while maintaining tolerance. This review will examine the data representing the research on prominent intervention agents n-3 polyunsaturated fatty acids (PUFA), micronutrients (zinc, vitamins D and E), and functional foods including probiotics and tea components for their immunological effects, working mechanisms, and clinical relevance. Many of these nutritive and non-nutritive food components are related in their functions to maintain or improve immune function including inhibition of pro-inflammatory mediators, promotion of anti-inflammatory functions, modulation of cell-mediated immunity, alteration of antigen-presenting cell functions, and communication between the innate and adaptive immune systems. Both animal and human studies present promising findings suggesting a clinical benefit of vitamin D, n-3 PUFA, and green tea catechin EGCG in autoimmune and inflammatory disorders, and vitamin D, vitamin E, zinc, and probiotics in reduction of infection. However, many studies report divergent and discrepant results/conclusions due to various factors. Chief among them, and thus call for attention, includes more standardized trial designs, better characterized populations, greater consideration for the intervention doses used, and more meaningful outcome measurements chosen.

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Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance

Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients

Toxic effect of zinc on NF-κB, IL-2, IL-2 receptor α, and TNF-α in HUT-78 (Th0) cells

Data on performance characteristics of flexible sigmoidoscopy (FS) between age groups are limited. This study evaluates screening FS in subjects ≥75 years of age (elderly) compared with ages 50–74 years (general screening population). Data were collected on patient characteristics, insertion depth, procedural difficulties, complications, and endoscopic findings. There was an increased rate of endoscopist-reported limitations (50.4% vs. 34.9%; P = 0.0001) and incomplete examinations (15.6% vs. 5.4%; P = 0.0001) in the elderly cohort relative to subjects aged 50–74. The complication rate (1.0% vs. 1.5%; P = 0.53), adenoma detection rate (7.2% vs. 5.6%; P = 0.213), and advanced adenoma detection rate (0.71% vs 0.65%; P = 0.86) were similar. More carcinomas were detected in the elderly (0.53% vs. 0.06%; P = 0.042). Factors associated with incomplete examinations in the elderly included age, female gender, and poor bowel preparation. Despite technical difficulties, FS in the elderly is safe and detects significant pathology.

Flexible sigmoidoscopy for colorectal cancer screening in the elderly.

1. Reuben DB, Hirsch SH, Zhou K et al. The effects of megestrol acetate suspension for elderly patients with reduced appetite after hospitalization: A phase II randomized clinical trial. J Am Geriatr Soc 2005;53:970–975. 2. Lopez AP, Roque Figuls M, Cuchi GU et al. Systematic review of megestrol acetate in the treatment of anorexia–cachexia syndrome. J Pain Symptom Manage 2004;27:360–369. 3. Graham KK, Mikolich DJ, Fisher AE et al. Pharmacologic evaluation of megestrol acetate oral suspension in cachetic AIDS patients. J Acquir Immune Defic Syndr 1994;7:580–586. 4. Haren MT, Thomas DR, Morley JE et al. Megestrol acetate is absorbed more rapidly and more completely from new NanoCrystal dispersion than from the old form (Abstract #P3–286). The Endocrine Society’s 87th Annual Meeting, San Diego, CA: June 4–7, 2005. 5. Wilson MG, Thomas DR, Chibnall JT et al. Appetite assessment: Simplified nutritional appetite questionnaire predicts weight loss in community dwelling adults and nursing home residents. Am J Clin Nutr in press. 6. Karcic E, Philpot C, Morley JE. Treating malnutrition with megestrol acetate: Literature review and review of our experience. J Nutr Health Aging 2002;6: 191–200. 7. Mann M, Koller E, Murgo A et al. Glucocorticoid activity of megestrol: A summary of Food and Drug Administration experience and a review of the literature. Arch Intern Med 1997;157:1651–1656. 8. Loprinzi CL, Fonseca R, Jensen MD. Megestrol acetate-induced adrenal suppression. J Clin Oncol 1996;14:689.

https://agsjournals.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1532-5415.2005.00575_4.x

Anupam Suneja

Papers

Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients

Toxic effect of zinc on NF-κB, IL-2, IL-2 receptor α, and TNF-α in HUT-78 (Th0) cells

Flexible sigmoidoscopy for colorectal cancer screening in the elderly.

Megestrol acetate use for anorexia in the older subject

Beneficial Effect of Zinc Supplementation on Oxidative Stress, Cytokines, and NF-κB DNA Binding in Sickle Cell Disease Patients.