Grape Seed Extract Reduces the Degree of Atherosclerosis in Ligature-Induced Periodontitis in Rats - An Experimental Study.

The associations between periodontitis and cardiovascular diseases have been intensely studied in recent years. Oxidative stress is involved in the initiation and both progression of periodontitis and atherosclerosis. Antioxidants can reduce the effects of oxidative stress on inflammatory diseases. Our aim was to measure the effects of a grape seed extract (GSE), rich in antioxidants, on atherosclerosis caused by ligature-induced periodontitis in rats. Thirty male Wistar rats were randomly divided into three groups of 10: control group, periodontitis group, and periodontitis group treated with GSE (GSE group). Periodontitis was induced by placing an orthodontic wire around the cervix of the first mandibular molar and keeping it in place for 4 weeks. On days 1, 7 and 28, blood samples were taken to assess oxidative stress and inflammation markers (malondialdehyde and glutathione - MDA, reduced glutathione - GSH, C reactive protein) and lipids. After 4 weeks, the animals were euthanized, and aortas were collected for histopathologic examination. MDA was significantly higher in Periodontitis group compared to the other groups only at day 7. GSH was significantly increased in the Control and GSE groups on days 1 and 7, compared to Periodontitis group and on day 28 higher in GSE vs. Periodontitis groups. C reactive protein was significantly increased in the Periodontitis group on days 1 and 7 compared to both groups. Cholesterol was significantly decreased in the aortas of GSE group at day 28 compared to the Periodontitis group. Oral administration of a grape seed extract reduces the oxidative stress, inflammation and atherosclerosis in a rat model of ligature-induced periodontitis.

Efficiency of photodynamic therapy on WM35 melanoma with synthetic porphyrins: Role of chemical structure, intracellular targeting and antioxidant defense.

Photodynamic therapy (PDT) could be an adjuvant therapy in melanoma, an aggressive cancer that arises from melanocytes. Several reports showed encouraging results of the efficacy of PDT in melanoma on experimental models and in clinical trials. Therefore, we studied the efficacy of two derivatives of tetraphenylporphyrin (TPP): meso-5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin (THOPP) and meso-5-(4-hydroxyphenyl)-10,15,20-tris (4-methoxyphenyl) porphyrin (THOMPP) as photosensitizers for PDT, compared to FDA approved delta aminolevulinic acid (ALA) against a lightly pigmented, melanoma cell line, WM35, in vitro. Both porphyrins were more efficient as photosensitizers, compared to ALA, without dark toxicity. The efficiency depended on the intracellular localization and the molecule structure. THOPP, the most efficient porphyrin localized mainly in mitochondria, while THOMPP accumulated in lysosomes; both showed melanosomal localization. The symmetric THOPP molecule was able to generate increased oxidative stress damage and apoptosis. THOPP also induced a low effect on the defense mechanisms like antioxidant enzyme SOD (superoxide dismutase), NF-kB (nuclear transcription factor kB) activation and MITF (microphthalmia transcription factor). The lower efficiency of the asymmetric molecule, THOMPP was probably due to a diminished photoactivation, which led to a lower ROS induced damage, combined with higher activation of the defense mechanisms.

Influence of Genista tinctoria L. or methylparaben on subchronic toxicity of bisphenol A in rats.

OBJECTIVE: To evaluate the influence of an extract of Genista tinctoria L. herba (GT) or methylparaben (MP) on histopathological changes and 2 biomarkers of oxidative stress in rats subchronicly exposed to bisphenol A (BPA). METHODS: Adult female Wistar rats were orally exposed for 90 d to BPA (50 mg/kg), BPA+GT (35 mg isoflavones/kg) or BPA+MP (250 mg/kg). Plasma and tissue samples were taken from liver, kidney, thyroid, uterus, ovary, and mammary gland after 30, 60, and 90 d of exposure respectively. Lipid peroxidation and in vivo hydroxyl radical production were evaluated by histological analysis along with malondialdehyde and 2,3-dihydroxybenzoic acid detection. RESULTS: The severity of histopathological changes in liver and kidneys was lower after GT treatment than after BPA or BPA+MP treatment. A minimal thyroid receptor antagonist effect was only observed after BPA+MP treatment. The abnormal folliculogenesis increased in a time-dependent manner, and the number of corpus luteum decreased. No significant histological alterations were found in the uterus. The mammary gland displayed specific estrogen stimulation changes at all periods. Both MP and GT revealed antioxidant properties reducing lipid peroxidation and BPA-induced hydroxyl radical generation. CONCLUSION: GT L. extract ameliorates the toxic effects of BPA and is proved to have antioxidant potential and antitoxic effect. MP has antioxidant properties, but has either no effect or exacerbates the BPA-induced histopathological changes.

Inhibition of UVB-induced skin phototoxicity by a grape seed extract as modulator of nitrosative stress, ERK/NF-kB signaling pathway and apoptosis, in SKH-1 mice.

Molecular mechanisms concerning the modulation of nitrosative stress, signal transduction and proliferation/apoptosis by a grape seed extract, Burgund Mare variety (BM), in SKH-1 mice exposed to UVB, were investigated. The animals were irradiated with single and multiple doses of UVB in 10 consecutive days. In each experiment were used five groups of animals: control, vehicle, UVB irradiated, vehicle+UVB, BM+UVB. The extract was applied topically, 30 min before each UVB exposure, in a dose of 4 mg total polyphenols/cm(2). BM remarkably inhibited UVB-induced activation of inducible nitric oxide synthase (iNOS) and therefore generation of nitric oxide (NO) and nitrotyrosine, in a UVB single dose regimen. BM also suppressed NF-kB activation by UVB but did not affect the activity of total ERK 1/2. In multiple UVB irradiations, BM increased NO formation and total ERK 1/2 activity and reduced iNOS activity and nitrotyrosine levels, inhibited cell proliferation, diminished p53 and caspase-3 immunoreactivities and increased the percentage of Bcl-2 positive cells. We concluded that BM modulates the apoptotic response of SKH-1 mice skin in UVB irradiation by the inhibition of p53, caspase-3, Bax/Bcl-2 and proliferating cell nuclear antigen expressions, as well as by reducing the activation of iNOS and NF-kB.

Photochemoprotective effect of Calluna vulgaris extract on skin exposed to multiple doses of ultraviolet B in SKH-1 hairless mice.

UVB is a major cause of nonmelanoma skin cancer in humans. Photochemoprevention represents an important strategy in protecting the skin against the detrimental effects of ultraviolet B (UVB). We investigated the activity of Calluna vulgaris (Cv) delivered via a hydrogel on 3 main pathways (oxidative stress, inflammation, DNA damage) on skin exposed to multiple doses of UVB in SKH-1 mice. Fifty female mice were divided randomly into 5 groups: control, vehicle, UVB irradiated, Cv + UVB irradiated, and Cv + vehicle + UVB irradiated. The extract was applied topically on the skin in a dose of 4 mg polyphenols/cm2 30 minutes before each UVB (240 mJ/cm2) exposure over 10 consecutive days. Malondialdehyde, reduced glutathione, tumor necrosis factor-α, interleukin-6, cyclobutane pyrimidine dimer (CPD) levels, sunburn cell formation and epidermal thickness, and the number of epidermal cell layers in skin were evaluated 24 hours after the last treatment. UVB increased cytokine levels (P < 0.001), formation of CPDs (P < 0.001) and sunburn cells (P < 0.001), and the epidermal thickness and number of epidermal cell layers (P < 0.001) compared with the control group. The topical application of Cv protected the skin against inflammation and DNA damage, as shown by a decreased number of CPDs (P < 0.001) and sunburn cells (P < 0.001). The administration of Cv via hydrogel may be a viable method for chemoprevention..

The effects of grape seeds polyphenols on SKH-1 mice skin irradiated with multiple doses of UV-B.

The study investigated the protective activity of red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on multiple doses of ultraviolet radiation (UV)-B-induced deleterious effects in SKH-1 mice skin. Eighty 8-weeks-old female SKH-1 mice were divided into 8 groups: control, vehicle, UV-B irradiated, vehicle+UV-B irradiated, BM 2.5mg polyphenols (PF)/cm(2)+UV-B irradiated, BM 4 mg PF/cm(2)+UV-B irradiated, UV-B+BM 2.5mg PF/cm(2), UV-B+BM 4 mg PF/cm(2). The extract was applied topically before or after each UV-B exposure (240 mJ/cm(2)), for 10 days consecutively. The antioxidant activity of BM extract is higher than gallic acid (k(BM)=0.017, k(gallic acid)=0.013). Multiple doses of UV-B generated the formation of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, increased glutathione peroxidase (GPx) and catalase (CAT) activities respectively glutathione (GSH) and IL-1ß levels in skin. In group treated with 2.5mg PF/cm(2) before UV-B irradiation BM extract inhibited UV-B-induced sunburn cells, restored the superoxide dismutase (MnSOD) activity, increased insignificantly CAT and GPx activities and reduced IL-1ß level. The BM 4.0 mg PF/cm(2) treatment decreased GSH level and reduced the percentage of CPDs positive cells in skin. Both doses of BM extract administered after UV-B irradiation increased the MnSOD and GPx activities and reduced the formation of sunburn cells in skin. Our results suggest that BM extract might be a potential chemo-preventive candidate in reducing the oxidative stress and apoptosis induced by multiple doses of UV-B in skin.