Is the clinical course of non-arteritic ischemic optic neuropathy associated with oxidative damage and the dynamics of the antioxidant response?

PURPOSE: Oxidative stress is known to be a decisive factor in the wide etiopathogenesis of optic neuropathy. This study aimed to comprehensively evaluate the interaction of optic neuropathy's clinical course with systemic oxidative damage and antioxidant response dynamics in a large series. METHODS: This case-controlled clinical study included 33 non-arteritic anterior ischemic optic neuropathy (NAION) patients and 32 healthy individuals. Extensive systemic oxidation profiles were statistically compared between the two groups, and correlations between the clinical and biochemical data in the study group were analyzed. RESULTS: Vitamin E and malondialdehyde (MDA) levels were significantly higher in the study group. Significant correlations were observed in the analyses between clinical findings and oxidative stress parameters. Correlations between vitamin E and intraocular pressure (IOP), between B12 and cup-to-disk ratio (c/d), between antioxidant glutathione and superoxide dismutase (SOD) enzyme systems, and between uric acid (UA) and age were found to be very significant. As significant correlations were found in either clinical and biochemical data or in oxidative stress parameters, correlations between vitamin E and cholesterol, MDA were found to be very significant. CONCLUSIONS: This study not only supplies significant information regarding oxidative damage and antioxidant response in NAION, but also points out the specific interactions of neuromodulators, like vitamin E, in intracellular signaling pathways and regulation mechanisms. A better reading of these connections may help improve diagnosis, follow-ups and treatment criteria and strategies.

Melatonin Prevents UVB-Induced Skin Photoaging by Inhibiting Oxidative Damage and MMP Expression through JNK/AP-1 Signaling Pathway in Human Dermal Fibroblasts.

Exposure to ultraviolet (UV) irradiation causes damage to the skin and induces photoaging. UV irradiation stimulates production of reactive oxygen/nitrogen species, which results in activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) in fibroblasts. MAPKs are responsible for activation of activator protein-1 (AP-1), which subsequently upregulates expression of matrix metalloproteinases (MMPs). Melatonin is a potent free radical scavenger which is known to have photoprotective effects. The aim of this study is to investigate the underlying molecular mechanisms for the photoprotective effects of melatonin in UVB-irradiated primary human dermal fibroblasts (HDFs) in terms of EGFR activation, oxidative/nitrosative damage, JNK/AP-1 activation, MMP activities, and the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and type I procollagen (PIP-C). In this study, HDFs were pretreated with 1 µM of melatonin and then irradiated with 0.1 J/cm2 of UVB. Changes in the molecules were analyzed at different time points. Melatonin inhibited UVB-induced oxidative/nitrosative stress damage by reducing malondialdehyde, the ratio of oxidized/reduced glutathione, and nitrotyrosine. Melatonin downregulated UV-induced activation of EGFR and the JNK/AP-1 signaling pathway. UVB-induced activities of MMP-1 and MMP-3 were decreased and levels of TIMP-1 and PIP-C were increased by melatonin. These findings suggest that melatonin can protect against the adverse effects of UVB radiation by inhibiting MMP-1 and MMP-3 activity and increasing TIMP-1 and PIP-C levels, probably through the suppression of oxidative/nitrosative damage, EGFR, and JNK/AP-1 activation in HDFs.

Relationship of Wnt pathway activity and organ involvement in scleroderma types.

OBJECTIVE: Scleroderma (SSc) is a chronic inflammatory autoimmune disease characterized by fibrosis in the skin and internal organs. In SSc, the heart, lung, kidney, gastrointestinal (GIS) system, muscle, and peri-articular structures are damaged. There is no study of the relationship between SSc type, stage, pathogenesis, organ involvement, and Wnt signaling. In this study, we aimed to show the relationship of the Wnt gene family and antagonists in SSc subtypes and different organ involvement. METHODS: Eighty-five SSc patients and 77 controls were included in this study. The gene expressions and protein levels of the Wnt family and antagonists were analyzed from blood samples. The relationship between these parameters and disease stage, type, and organ involvement were evaluated. RESULTS: Wnt-1, Wnt-10b, Wnt-2, and Wnt-6 gene expressions are increased and Axin-2, DKK-1, and Kremen protein expressions are decreased in SSc. Wnt-3a and Wnt-10a gene expressions are increased in generalized SSc compared to limited SSc. Wnt-1, Wnt-2 gene expressions are increased significantly in pulmonary arterial hypertension (PAH)(+) SSc compared to PAH(-) SSc. There was a positive correlation between the modified Rodnan skin score and Wnt-2 in SSc. There was a significant positive correlation between GIS involvement score and Wnt-1, Wnt-2, Wnt-4, Wnt-8a, Wnt-9b in SSc. CONCLUSION: Wnt-1 and Wnt-2 were found higher in scleroderma and organ involvement. They may play a role in the pathogenesis of the disease.

Melatonin attenuates the detrimental effects of UVA irradiation in human dermal fibroblasts by suppressing oxidative damage and MAPK/AP-1 signal pathway in vitro.

BACKGROUND: People living in Mediterranean countries are mostly exposed to solar ultraviolet (UV) radiation that damages skin and results in photoaging which involves activation of epidermal growth factor receptor (EGFR) and downstream signal transduction through mitogen-activated protein kinases (MAPKs) in fibroblasts. Generation of reactive oxygen/nitrogen species by UV radiation is also critical for EGFR and MAPKs activation. MAPKs are responsible for activation of AP-1 subunits in the nucleus which induce matrix metalloproteinases. Melatonin, along with its metabolites, are known to be the most effective free radical scavenger and protective agent due to its ability to react with various radicals, lipophilic/hydrophilic structures. OBJECTIVES: In this study, we investigated the effects of melatonin on UVA-irradiated primary human dermal fibroblasts (HDFs) by following the alteration of molecules from cell membrane to the nucleus and oxidative/nitrosative damage status of the cells in a time-dependent manner which have not been clearly elucidated yet. METHODS: To mimic UVA dosage in Mediterranean countries, HDFs were exposed to UVA with sub-cytotoxic dosage (20 J/cm2 ) after pretreatment with melatonin (1 µmol/L) for 1 hour. Changes in the activation of the molecules and oxidative/nitrosative stress damage were analyzed at different time points. RESULTS: Our results clearly show that melatonin decreases UVA-induced oxidative/nitrosative stress damage in HDFs. It also suppresses phosphorylation of EGFR, activation of MAPK/AP-1 signal transduction pathway and production of matrix metalloproteinases in a time-dependent manner. CONCLUSION: Melatonin can be used as a protective agent for skin damage against intracellular detrimental effects of relatively high dosage of UVA irradiation.

The role of resveratrol on full - Thickness uterine wound healing in rats.

OBJECTIVE: Healing of the uterus after cesarean section and myomectomy operation is clinically important. In this study, we aimed to investigate the effects of resveratrol (3,5,4'-o-trihydroxystilbene) on the wound healing process of the uterus in rats treated with resveratrol following full thickness injury of the uterus. MATERIALS AND METHODS: Twenty-one female wistar albino rats were divided randomly into three groups (1) control group with no intervention (2) injury group with uterine full thickness injury (3) resveratrol group with uterine full thickness injury and treated with resveratrol. Resveratrol was injected by oral gavage at the doses of 0.5 mg/kg/day for 30 days following uterine full thickness injury. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) distributions were assessed using the immunohistochemical methods in tissue and ELISA methods in the tissue homogenate. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated with colorimetric method and malondialdehyde (MDA) levels also were measured using high performance liquid chromatography in the tissue homogenate. The effects of resveratrol on the uterine histology also were evaluated histologically with the light microscopy. RESULTS: Histological evaluation and immunohistochemical evaluations showed that treatment with a resveratrol significantly increased the thickness of the uterine wall and VEGF expression and decreased expression PDGF during wound healing. Biochemically, GPx and SOD activities were increased significantly after treatment with resveratrol. Additionally, resveratrol administration decreased MDA levels. CONCLUSION: These results showed that the antioxidant effects of resveratrol has been shown to have a positive influence on wound healing of the uterus.