allopurinol and Dermatitis

Dermatitis, like inflammation, is a group of common dermatological symptoms and may be associated with systemic and skin diseases. The objective of the current study is to evaluate the potential anti-inflammatory effect of the topical allopurinol against inflammation like skin dermatitis induced by1-isobutyl-1H-imidazo [4,5-c]quinolin-4-amine (IQA) in mice model. The current study allocated the thirty-two mice into four groups (n=8) as follows: i) control group, mice where a white petroleum jelly base applied topically on the dorsal of mice once daily; ii) induction group, mice were received IQA cream (62.5 mg) of (5%) on their back once daily; and iii) the treatment group, mice were treated with both (62.5 mg) of (5%) IQA and (5%) allopurinol gel topically; the betamethasone group, mice were treated with both (62.5 mg) of (5%) IQA and betamethasone ointment topically. All groups were treated daily for seven days period. The allopurinol-treated group exerted non-significant differences compared with the induction group in both visional and histopathological changes. The present study revealed that the allopurinolgel (5%) did not affect skin inflammation- induced by IQA in the laboratory mice.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents; Betamethasone; Dermatitis; Disease Models, Animal; Inflammation; Mice

Vitamin E (alpha-tocopherol) is a promising chemopreventive and pharmacologically safe agent, which can be exploited or tested against skin cancer. It is an established antioxidant with an ability to ameliorate the UV-induced skin damage and chemically induced inflammation in lungs. However, there are some conflicting reports about its role as a modulator of chemically induced promotion. We evaluated its efficacy in preventing the inflammatory and oxidative stress responses in a double 12-O-tetradecanoylphorbol-13-acetate (TPA) application tumor skin promotion protocol. Double application of TPA was undertaken to produce massive inflammatory and oxidative stress responses. Topical TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion. Vitamin E application 30 min prior to TPA treatment (10 nmol) inhibited induction of hydrogen peroxide, myeloperoxidase (MPO) activity, xanthine oxidase (XO) activity and lipid peroxidation (LPO). Vitamin E also positively modulated altered antioxidants of mouse skin. Histological examination also revealed marked improvement. These results confirm the efficacy of vitamin E against early inflammatory and oxidative stress responses, which are hallmark of tumor promotion and provide rational basis for chemopreventive action of vitamin E in skin cancer.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Dermatitis; Female; Hydrogen Peroxide; Lipid Peroxidation; Mice; Mice, Inbred SENCAR; Oxidative Stress; Peroxidase; Skin Neoplasms; Tetradecanoylphorbol Acetate; Vitamin E; Xanthine Oxidase

Free radical formation has been investigated in diverse experimental models of LPS-induced inflammation. Here, using electron spin resonance (ESR) and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, we have detected an ESR spectrum of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in the lipid extract of mouse skin treated with LPS for 6 h. The ESR spectrum was consistent with the trapping of lipid-derived radical adducts. In addition, a secondary radical-trapping technique using dimethyl sulfoxide (DMSO) demonstrated methyl radical formation, revealing the production of hydroxyl radical. Radical adduct formation was suppressed by aminoguanidine, N-(3-aminomethyl)benzylacetamidine (1400W), or allopurinol, suggesting a role for both inducible nitric oxide synthase (iNOS) and xanthine oxidase (XO) in free radical formation. The radical formation was also suppressed in iNOS knockout (iNOS(-/-)) mice, demonstrating the involvement of iNOS. NADPH oxidase was not required in the formation of these radical adducts because the ESR signal intensity was increased by LPS treatment in NADPH oxidase knockout (gp91(phox-/-)) mice as much as it was in the wild-type mouse. Nitric oxide (*NO) end products were increased in LPS-treated skin. As expected, the *NO end products were not suppressed by allopurinol but were by aminoguanidine. Interestingly, nitrotyrosine formation in LPS-treated skin was also suppressed by aminoguanidine and allopurinol independently. Pretreatment with the ferric iron chelator Desferal had no effect on free radical formation. Our results imply that both iNOS and XO, but neither NADPH oxidase nor ferric iron, work synergistically to form lipid radical and nitrotyrosine early in the skin inflammation caused by LPS.

Topics: Allopurinol; Animals; Dermatitis; Electron Spin Resonance Spectroscopy; Enzyme Inhibitors; Free Radicals; Guanidines; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; Skin; Xanthine Oxidase

In this study we attempted to demonstrate whether endothelial cell nitric oxide synthase (eNOS) and xanthine oxidase (XO) could be activated to release nitric oxide (NO) and peroxynitrite (ONOO-) following exposure to ultraviolet B (UVB) radiation and to define whether this light-induced response could be involved in the pathogenesis of sunburn erythema and inflammation. Treatment of human endothelial cells with UVB (290-320 nm) radiation (up to 100 mJ/cm2) resulted in an increase of both NO and ONOO- release that was inhibited by NG-monomethyl-L-arginine (L-NMMA). Treatment of cell cytosol with various doses of UVB radiation (up to 20 mJ/cm2) resulted in a threefold increase of XO activity that was inhibited (approximately 90% by oxypurinol. In reconstitution experiments, when purified eNOS was added to purified XO, an almost fourfold increase in ONOO- production at 20 mj/cm2 UVB radiation was observed. UVB radiation (100 mg/cm2) decreased cell membrane fluidity, indicating changes in the physicochemical characteristics of the membranes. In in vivo experiments, when human volunteers were subjected to UVB light, a protection factor (PF) of 3.90 +/- 0.85 was calculated when an emulsified cream formulation containing nitro-L-arginine (L-NA; 2%) and L-NMMA (2%) was applied to their skin. The present studies indicate that UVB radiation acts as a potent stimulator of eNOS and XO in human endothelial cells. The cytotoxic effects of NO and ONOO- may be the main factors in the integrated response of the skin leading to vasodilatation, the first key event of erythema production and the inflammation process.

Topics: Cells, Cultured; Dermatitis; Endothelium, Vascular; Enzyme Activation; Erythema; Humans; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Sunburn; Ultraviolet Rays; Umbilical Veins; Xanthine Oxidase

It is well known that retinoids are effective in the treatment of various dermatological disorders. It has been reported that retinoids have inhibitory effects on the generation of superoxide (O2-) by stimulated polymorphonuclear leukocytes (PMNs). In the present study, we investigated the effects of retinoids on the generation of O2- and other reactive oxygen species (ROS), including OH., H2O2 and chemiluminescence, by zymosan-stimulated PMNs and in the xanthine-xanthine oxidase system, because these potent ROS may play an important role in PMN-mediated skin inflammation. It was found that some retinoids had antioxidant effects in the PMN system; however, apart from the effect of tretinoin and Ro 10-1670 on OH. generation, none of the retinoids studied inhibited ROS generation in the xanthine-xanthine oxidase system. On the basis of these results, we discuss a possible mechanism connected with the role of ROS by which retinoids have favourable effects on several inflammatory skin disorders.

Topics: Antioxidants; Dermatitis; Etretinate; Humans; Hydrogen Peroxide; Hydroxides; Hydroxyl Radical; In Vitro Techniques; Luminescent Measurements; Neutrophils; Retinoids; Superoxides; Xanthine; Xanthine Oxidase; Xanthines; Zymosan

Topics: Allopurinol; Animals; Dermatitis; Dog Diseases; Dogs; Female; Uric Acid; Urinary Calculi