metallothionein and Skin-Diseases

Information is conflicting as to whether nitric oxide plays a role in the pathogenic mechanisms of zinc deficiency. Our series of research using a rat model demonstrated that inducible nitric oxide synthase in the intestine is upregulated by zinc deficiency when challenged by the injection of IL-1alpha, and the systemic administration of nitric oxide synthase inhibitor attenuates both intestinal damage and inflammatory skin lesions induced by zinc deficiency. Evidence from both transcription and translation levels indicates that inducible nitric oxide synthase, one of three nitric oxide synthase isoforms, has already been induced in the skin and intestine of zinc-deficient animals, whereas it is not generally expressed in normal tissues. On the other hand, total nitric oxide synthase activity in the intestine of zinc-deficient animals is significantly lower than that in controls, indicating that zinc deficiency may induce a potential vulnerability to nitric oxide rather than an absolute increase of nitric oxide synthase activities. Tissue zinc and metallothionein levels are significantly decreased in zinc-deficient rats, suggesting lowered antioxidative capability. Whether nitric oxide is destructive in inflammation may depend on the status of homeostasis such as the zinc level of tissues and the balance between the three nitric oxide synthase components, although identifying an absolute increase of nitric oxide production is of importance. Defining the role of nitric oxide provides the rationale for new strategies in zinc deficiency.

Topics: Apoptosis; Gastrointestinal Diseases; Humans; Intestines; Metallothionein; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Skin; Skin Diseases; Zinc

The requirement of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, and chronic renal diseases; use of certain drugs such as penicillamine and, in some cases, diuretics; and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during growth. The clinical manifestations of severe zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, and hypogonadism in males; zinc deficiency can be fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and humans, probably because zinc is needed for protein and DNA synthesis and cell division. The effects of zinc and growth hormone on growth appear to be independent of each other in experimental animals. Whether zinc is required for the metabolism of somatomedin needs further investigation. Thyroid and adrenal functions do not appear to change as a result of zinc deficiency. Glucocorticoids may have an effect on zinc metabolism, although the clinical relevance of this effect is not known at present. In contrast, testicular function is affected adversely as a result of zinc deficiency in both humans and experimental animals. The effect appears to be a direct one since the hypothalamic-pituitary axis is intact, and may relate to the reduction in testicular size as a result of the need for zinc in cell division. In addition, zinc is required for the function of several testicular enzymes, although a specific role in steroidogenesis has not been identified. Zinc appears to have a role in the modulation of prolactin secretion, in the secretion and action of insulin, and in the production and biologic effects of thymic hormones. It is clear that the endocrine consequences of zinc deficiency are multiple, and that continued investigation should provide additional pathophysiologic and therapeutic i

Topics: Burns; Cell Membrane; Chronic Disease; Endocrine Glands; Enzymes; Female; Gastrointestinal Diseases; Genetic Diseases, Inborn; Growth; Humans; Immunity; Kidney Diseases; Metallothionein; Nucleic Acids; Pregnancy; Skin Diseases; Zinc

The goji berry, Lycium barbarum, has long been recognised in traditional Chinese medicine for various therapeutic properties based on its antioxidant and immune-modulating effects. This study describes the potential for orally consumed goji berry juice to alter the photodamage induced in the skin of mice by acute solar simulated UV (SSUV) irradiation. In Skh:hr-1 hairless mice, 5% goji berry juice significantly reduced the inflammatory oedema of the sunburn reaction. Dilutions of goji berry juice between 1% and 10% dose-dependently protected against SSUV-induced immunosuppression, and against suppression induced by the mediator, cis-urocanic acid, measured by the contact hypersensitivity reaction. The immune protection could not be ascribed to either the minor excipients in the goji juice, pear and apple juice, nor the vitamin C content, nor the preservative, and appeared to be a property of the goji berry itself. Antioxidant activity in the skin was demonstrated by the significant protection by 5% goji juice against lipid peroxidation induced by UVA radiation. Furthermore, two known inducible endogenous skin antioxidants, haem oxygenase-1 and metallothionein, were found to be involved in the photoimmune protection. The results suggest that consumption of this juice could provide additional photoprotection for susceptible humans.

Topics: Animals; Antioxidants; Beverages; Drinking; Edema; Female; Heme Oxygenase-1; Hypersensitivity; Immunosuppression Therapy; Inflammation; Lipid Peroxidation; Lycium; Metallothionein; Mice; Mice, Hairless; Oleic Acids; Oxidative Stress; Radiation Injuries, Experimental; Skin Diseases; Sunburn; Ultraviolet Rays

Topics: Adult; Humans; Male; Metallothionein; Sarcoidosis; Skin; Skin Diseases; Tattooing

The expression and distribution of metallothionein (MT) in frozen sections of normal and pathological human skin was studied using the monoclonal antibody L2E3 directed against MT derived from human fetal liver. Immunohistochemical staining of normal fetal and adult skin revealed strong reactivity in basal keratinocytes of epidermis and outer hair root sheath, hair matrix cells and the secretory coil, but not the exocrine portion of eccrine glands; myoepithelial cells around apocrine sweat glands were similarly stained. In epidermal hyperplasia, variable numbers of suprabasal keratinocytes were stained, whereas in interface dermatitis, interrupted staining was found in the basal layer. Weak or scattered staining was observed in squamous tumours, whereas basal cell carcinomas did not show consistent staining. The distribution of MT in normal skin was in line with the germinative role of basal keratinocytes and hair matrix cells, whereas its distribution in hyperplastic epidermis was in line with experimental animal data, and reflected the increase in the germinative pool in these conditions. It is concluded that monoclonal antibody L2E3 may serve as a valuable immunohistochemical marker in diagnostic cutaneous pathology since it labels basal keratinocytes selectively, and since it discriminates between eccrine and apocrine sweat glands.

Topics: Adult; Antibodies, Monoclonal; Apocrine Glands; Eccrine Glands; Epidermis; Fetus; Hair; Humans; Hyperplasia; Immunohistochemistry; Infant, Newborn; Keratinocytes; Metallothionein; Skin; Skin Diseases; Tissue Distribution

Protective effects of Aloe arborescens (AA) on mouse skin injury induced by soft X-irradiation were examined. The mechanisms on radiation protection by measuring scavenge activity of activated oxygen, protective effects of nucleic acid, induction of antioxidative protein and so on were further investigated. Consequently a significant protective effect of skin injury was observed in AA S6-3-b. As the mechanisms of radiation protection in AA, the following matters were found. AA S6-3-b showed scavenge activity of hydroxyl radicals generated by Haber-Weiss reaction. AA S6-3-b suppressed the changes of activity in superoxide dismutase and glutathione peroxidase at 7d after soft X-irradiation. Metallothionein was induced in the skin and liver against normal mice at 24 h after administration of AA S6-3-b.

Topics: Aloe; Animals; Drugs, Chinese Herbal; Free Radical Scavengers; Glutathione Peroxidase; Liver; Male; Metallothionein; Mice; Plants, Medicinal; Radiation Injuries, Experimental; Radiation-Protective Agents; Skin; Skin Diseases; Superoxide Dismutase