Natural chemopreventive alternatives in oral cancer chemoprevention.

We studied the effect of grape seed extract Burgund Mare (BM) on oral carcinogenesis and compared it with that of curcumin (CU). Wistar rats were divided into six groups (n = 10): 4-nitro-quinoline-1-oxide (4NQO) oral carcinogenesis was induced to groups 1 - 5; groups 2 and 3 received BM and CU respectively during initiation and groups 4 and 5 BM and CU during post-initiation of carcinogenesis; group 6 represented the negative control group. Total malondialdehyde (MDA) and reduced glutathione (GSH) were assayed fluorometrically in oral tissue (gingival, jugal, palatal, lingual mucosa) and serum. Histopathological exam was performed and a dysplasia score given to each oral mucosal lesion. Ki67, cyclin D1, p63, Bcl2 and p53 were immunohistochemically evaluated. BM and CU reduced tissue MDA values elevated by 4NQO (P = 0.000). The difference between CU and BM effect was significant in the initiation (P = 0.02) but not in the post-initiation phase of carcinogenesis (P = 0.58). Tissue GSH levels decreased by 4NQO (P < 0.001) were not significantly modified by BM or CU. Serum MDA levels increased by 4NQO (P = 0.000) were significantly lowered by CU (P = 0.04) and BM (P = 0.04) during initiation and by CU during post-initiation of carcinogenesis (P = 0.01). CU was more potent than BM during post-initiation of carcinogenesis (P = 0.01). Serum GSH lowered by 4NQO (P = 0.55) was significantly decreased by BM and CU (P < 0.012), with no significant difference between groups receiving BM or CU. Moderate dysplasia was the most advanced dysplasia induced and gingival localization the most frequent. Both BM and CU lowered dysplasia scores, with BM being the most efficient during post-initiation of carcinogenesis (P = 0.001). Ki67, cyclin D1, p63, Bcl2 and p53 expression increased with dysplasia scores. BM showed chemopreventive properties during initiation and post-initiation of oral carcinogenesis, reducing local and general oxidative stress and the intensity of dysplasia. During post-initiation of carcinogenesis BM and CU exhibited similar effects.

In vitro studies on the mechanisms involved in chemoprevention using Calluna vulgaris on vascular endothelial cells exposed to UVB.

The study aims to investigate the mechanisms involved in the in vitro effect of UVB on endothelial vascular cells (HUVECs) pretreated with a photochemopreventive agent, the Calluna vulgaris (Cv) extract. Two concentrations of Cv, below the limit of cytotoxicity IC50 (2.5 and 7.5 µg GAE/ml) and two doses of UVB (50 and 100 mJ/cm(2)) were used. Oxidative stress parameters were quantified at 1 h and 24 h after irradiation and apoptosis, DNA damage and the induction/activation of NF-κB were evaluated at 24 h. UVB exposure led to the formation of lipid peroxides in a dose dependent manner (p<0.001), induced apoptosis, increased the γ-H2AX levels and the activation of NF-κB. Pretreatment with 2.5 µg GAE/ml Cv improved the antioxidant defense, protected against DNA lesions and was able to decrease cellular death at low dose of irradiation. 7.5 µg GAE/ml Cv was prooxidant, favored the formation of DNA lesions, amplified the NF-κB activation UVB-induced (p<0.01) and led to high levels of cellular death. Both doses of Cv inhibited caspase-3 activation. The modulatory effect of Cv extract on endothelial cells exposed to UVB depend on the concentration of Cv used. This study provides insides into the mechanisms triggered by UVB and antioxidants on skin endothelial cells.

Spironolactone and dimethylsulfoxide effect on glucose metabolism and oxidative stress markers in polycystic ovarian syndrome rat model.

Because polycystic ovarian syndrome (PCOS) is a risk factor for type 2 diabetes, the affected women can present frequently prediabetic states such as impaired fasting glycaemia and/or impaired glucose tolerance. The purpose of our study is to explore the effect of antiandrogenic spironolactone on glucose metabolism and oxidative stress (OS) parameters in oestradiol valerate (OV) induced PCOS rat model.72 female Wistar rats were distributed either to PCOS group (n=65, OV dissolved in sesame oil, 5 mg/0.4 ml), or to non-PCOS control group (n=7, sesame oil, 0.4 ml). After a month, ultrasound was performed to assess the ovarian morphology, and the results of an initial oral glucose tolerance test (OGTT) were used to identify the animals with altered glucose metabolism (AGM). Glucose transporter 4 (GLUT4) was evaluated from muscle biopsies, OS parameters were assessed from blood and muscle samples, and ovaries of 3 rats were removed for histopathological examination. Afterwards, the AGM group was divided in a treated PCOS group denoted as Sp+D (per os spironolactone dissolved in DMSO, 2 mg/0.2 ml), and a PCOS control treated with DMSO (0.2 ml). After one month of daily treatment, a final OGTT was performed. GLUT4 and OS parameters were again evaluated and ovaries were removed for histopathological examination.As compared to the values prior to the treatment, Sp+D reversed fasting hyperglycaemia (p<0.001), increased GLUT4 immunoreactivity in the perinuclear compartment (p<0.05) and translocation to plasmalemma (p<0.001) and improved superoxide dismutase (0.001

Antimicrobial activity of Mentha piperita and Saturenja hortensis in a murine model of cutaneous protothecosis.

BACKGROUND: To date there is no defined pharmacologic treatment protocol available against cutaneous protothecosis, which is difficult to combat using conventional drugs. OBJECTIVES: Our experiment aimed to comparatively investigate the effect of two essential oils (Mentha piperita and Saturenja hortensis) against cutaneous protothecosis experimentally induced by Prototheca zopfii in mice. MATERIALS AND METHODS: Immunosuppressed BALB/c female mice, were divided into six experimental groups, infected with P. zopfii, and then treated for 21 days against the infection. The effectiveness of the different treatments was assessed clinically and histologically by quantifying the degree of inflammation (immunohistochemical quantification of macrophages, T lymphocytes and neutrophils) and fibrosis. RESULTS: Skin lesions in experimental protothecosis from non-treated mice were more severe as compared to the four groups of treated animals. Both M. piperita and S. hortensis have proved to be efficient in vivo in the treatment of cutaneous protothecosis by reducing the clinical signs and significantly reducing the degree of inflammation (P<0.05 for the number of macrophages, T lymphocytes and neutrophils) and fibrosis as compared to untreated animals. CONCLUSION: Interestingly, our study shows that M. piperita and S. hortensis could represent a potential source of natural antimicrobial products in the treatment of cutaneous protothecosis.

Histopathological aspects and local implications of oxidative stress in patients with oral lichen planus.

Aerobic life is connected with continuous production of free radicals, particularly reactive oxygen species (ROS). Cells posses an enzymatic and non-enzymatic antioxidant system to maintain redox homeostasis. Oxidant-antioxidant imbalance resulting in excessive accumulation of ROS is defined as oxidative stress. Oral lichen planus (OLP) is a chronic inflammation of unknown etiology. Several researchers suggest that oxidative stress is implicated in the pathogenesis of this disorder. The aim of this study was to evaluate the histopathological alterations and the status of local oxidative stress and antioxidant defense system in patients with OLP. We evaluated and compared the local levels of oxidative stress biomarkers malondialdehyde (MDA) and glutathione (GSH) in patients with OLP with that of normal controls. Increased levels of MDA and decreased levels of GSH suggest the idea of oxidative stress implication in the pathogenesis of oral lichen planus.

Chemopreventive effects of Calluna vulgaris and Vitis vinifera extracts on UVB-induced skin damage in SKH-1 hairless mice.

Solar ultraviolet radiation (UV) is a major cause of non-melanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy in the management of cutaneous neoplasia. The study investigated the protective activity of Calluna vulgaris (Cv) and red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on UVB-induced deleterious effects in SKH-1 mice skin. Forty SKH-1 mice were randomly divided into 4 groups (n=10): control, UVB irradiated, Cv + UVB irradiated, BM+UVB irradiated. Both extracts were applied topically on the skin in a dose of 4 mg/40 µl/cm(2) before UVB exposure - single dose. The effects were evaluated in skin 24 hours after irradiation through the presence of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 levels. The antioxidant activity of BM extract was higher than those of Cv extract as determined using stable free radical DPPH assay and ABTS test. One single dose of UVB generated formation of CPDs (p<0.0001) and sunburn cells (p<0.0002) and increased the cytokine levels in skin (p<0.0001). Twenty hours following irradiation BM extract inhibited UVB-induced sunburn cells (p<0.02) and CPDs formation (p<0.0001). Pretreatment with Cv and BM extracts resulted in significantly reduced levels of IL-6 and TNF-α compared with UVB alone (p<0.0001). Our results suggest that BM extracts might be a potential candidate in preventing the damages induced by UV in skin.