Aluminum (Al) and indium (In) have embryotoxic, neurotoxic and genotoxic effects, oxidative stress being one of the possible mechanisms involved in their cytotoxicity. We have recently demonstrated that indium intraperitoneal (ip) administration induced histological disorganization of testicular tissue. In the present research we aimed at investigating the effect of Al and In ip administration on systemic and testicular oxidative stress status. Studies were performed on Wistar rats ip injected with Al, In or physiological solution for two weeks. Our results showed that In significantly decreased the absolute weight of testicles. Measurements of lactate dehydrogenase (LDH) and paraoxonase (PON) activities showed that In induced a significant augmentation in the first parameter but no changes were observed in the second. Both Al and In caused oxidative stress in testicles by increasing malondialdehyde (MDA) and protein carbonyls (PC) production. Concomitantly, thiol group (-SH) and glutathione (GSH) level were enhanced in the testicles. In the blood, while concentrations of MDA was not changed, those of GSH was significantly decreased in the Al and In groups. Our results indicated that Al and In cause oxidative stress both in blood and testicles but In has cytotoxic effect as well as negative impact on testicle weights. These findings could explain the testicular histological alterations previously described after In ip administration.

Single-walled carbon nanotubes (SWCNT) represent a material holding significant potential for biomedical applications. However, toxicity concerns have been issued. Still, evidences regarding their toxic effects following subcutaneous administration are still scarce. We aimed to evaluate the dynamics of plasma redox equilibrium within the first 48 hours after subcutaneous injection of SWCNT functionalized with single strand DNA (ssDNA-SWCNT).

The oxidative effects of photodynamic therapy with 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (TMP) and Zn-5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (ZnTMP) were evaluated in Wistar rats subcutaneously inoculated with Walker 256 carcinoma. The animals were irradiated with red light (λ = 685 nm; D = 50 J/cm2; 15 min) 3 h after intra-peritoneal administration of 10 mg/kg body weight of porphyrins. The presence of free radicals in tumours after photodynamic therapy with TMP and ZnTMP revealed by chemiluminescence of luminol attained the highest level at 18 h after irradiation. Lipid peroxides measured as thiobarbituric-reactive substances and protein carbonyls, which are indices of oxidative effects produced on susceptible biomolecules, were significantly increased in tumour tissues of animals 24 h after photodynamic therapy. The levels of thiol groups and total antioxidant capacity in the tumours were decreased. The activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were also increased in tumour tissues after photodynamic therapy. Increased levels of plasma lipid peroxides as well as changes in the levels of erythrocyte antioxidant enzyme activities suggest possible systemic effects of photodynamic therapy with TMP and ZnTMP.

Single-walled carbon nanotubes (SWCNTs) have been proposed for various medical applications. However, their safety for human administration has not been yet fully demonstrated. In vitro studies have pointed oxidative stress as a mechanism involved in their cytotoxic effects. In the present study we have evaluated the capacity of DNA functionalized SWCNTs to induce oxidative stress in blood after intraperitoneal (ip) administration in rats. The presence of SWCNTs in blood was confirmed by Raman spectroscopy 30 minutes after their ip administration. Oxidative stress parameters (malondialdehyde - MDA, protein carbonyls - PC, antioxidant capacity measured as hydrogen donating capacity - HD, sulfhydryl groups - SH, glutathione - GSH and nitrites - NO) were assessed in blood at 3, 6, 24, respectively, and 48 hours after ip injection. MDA, PC and NO exhibited a significant increase at 3-6 hours interval from exposure, followed by a recovery trend. The levels of HD reached a bottom level at 6 hours after administration, while SH strongly decreased at 3 hours interval and increased slightly up to 48 hours without attending the initial values. GSH level recorded an increasing tendency at the 3rd hour, an incomplete recovery process at 24 hours followed by a secondary significant increase following a 48-hour interval. Significant inverse correlations were obtained between the PC and SH levels and between the NO and HD values. In conclusion, the ip administration of DNA functionalized SWCNT in rats results in oxidative stress generation in plasma, with a transient pattern of evolution.

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.

Photodynamic therapy (PDT) mediated by oxidative stress causes direct tumor cell damage as well as microvascular injury. To improve this treatment new photosensitizers are being synthesized and tested. We evaluated the effects of PDT with 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on tumor levels of malondialdehyde (MDA), reduced glutathione (GSH) and cytokines, and on the activity of caspase-3 and metalloproteases (MMP-2 and -9) and attempted to correlate them with the histological alterations of tumors in 3-month-old male Wistar rats, 180 ± 20 g, bearing Walker 256 carcinosarcoma. Rats were randomly divided into five groups: group 1, ZnTMPP+irradiation (IR) 10 mg/kg body weight; group 2, TMPP+IR 10 mg/kg body weight; group 3, 5-aminolevulinic acid (5-ALA+IR) 250 mg/kg body weight; group 4, control, no treatment; group 5, only IR. The tumors were irradiated for 15 min with red light (100 J/cm², 10 kHz, 685 nm) 24 h after drug administration. Tumor tissue levels of MDA (1.1 ± 0.7 in ZnTMPP vs 0.1 ± 0.04 nmol/mg protein in control) and TNF-α (43.5 ± 31.2 in ZnTMPP vs 17.3 ± 1.2 pg/mg protein in control) were significantly higher in treated tumors than in controls. Higher caspase-3 activity (1.9 ± 0.9 in TMPP vs 1.1 ± 0.6 OD/mg protein in control) as well as the activation of MMP-2 (P < 0.05) were also observed in tumors. These parameters were correlated (Spearman correlation, P < 0.05) with the histological alterations. These results suggest that PDT activates the innate immune system and that the effects of PDT with TMPP and ZnTMPP are mediated by reactive oxygen species, which induce cell membrane damage and apoptosis.

Oxidative stress is related to the liver fibrosis, anticipating the hepatic stellate cells' (HSC) activation. Our aim was to correlate oxidative stress markers with the histological liver alterations in order to identify predictive, noninvasive parameters of fibrosis progression in the evolution of toxic hepatitis.CCl4 in sunflower oil was administered to rats intragastrically, twice a week. After 2, 3, 4 and 8 weeks of treatment, plasma levels of malondialdehyde (MDA), protein carbonyls (PC), hydrogen donor capacity (HD), sulfhydryl groups (SH), and glutathione (GSH) were measured and histological examination of the liver slides was performed. Dynamics of histological disorders was assessed by The Knodell score. Significant elevation of inflammation grade was obtained after the second week of the experiment only (p=0.001), while fibrosis started to become significant (p=0.001) after 1 month of CCl4 administration. Between plasma MDA and liver fibrosis development a good correlation was obtained (r=0.877, p=0.05). Correlation between PC dynamics and liver alterations was marginally significant for inflammation grade (r=0.756, p=0.138). HD evolution revealed a marginally inverse correlation with inflammation grade (r=-0.794, p=0.108). No correlations could be established for other parameters with either inflammation grade or fibrosis stage.Our study shows that MDA elevation offers the best prediction potential for fibrosis, while marginal prediction fiability could be attributed to high levels of plasma PC and low levels of HD.

Photodynamic therapy (PDT) is a promising therapy especially in skin cancer, using the systemic administration of a photosensitizer (PS), followed by the local irradiation of the tumor with visible light. The antitumor effects of PDT are determined especially by the generation of cytotoxic reactive oxygen species (ROS). The 5,10,15,20-tetra-sulfo-phenyl-porphyrin (TSPP) is a synthetic photosensitizer, which proved its efficiency in in vitro studies. Our study evaluates the effects of PDT with TSPP upon the tumor levels of ROS and upon the metalloproteinases 2 (MMP2) activities on Wistar male rats bearing 256 Walker carcinosarcoma in correlation with the accumulation of PS in the tumor and with the intratumor histological alterations. The evaluations were performed dynamically, at 3 hours, 6 hours, 24 hours and 14 days after the PDT with TSPP. Our results emphasize that 24 hours after the PDT with TSPP, the ROS generation increases, as revealed by protein carbonyls and malondialdehyde levels and the antioxidant capacity (hydrogen donors, thiol groups) decreases in the tumor tissue. These parameters were correlated with the appearance of the histological disorders. The MMP-2 activity increases exponentially in the 24 hours-14 days post PDT interval. PDT with TSPP offers, in vivo , consistent results regarding ROS generation, MMP2 activation and cytotoxic capacity.

International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S577-S578 Poster presentations P580 Experimental study regarding the antioxidant effects of some natural products A. Muresan, A. MuresanSearch for more papers by this authorC. Alb, C. AlbSearch for more papers by this authorD. Daicoviciu, D. DaicoviciuSearch for more papers by this authorA. Filip, A. FilipSearch for more papers by this authorS. Clichici, S. ClichiciSearch for more papers by this authorF. Galea Catoi, F. Galea CatoiSearch for more papers by this authorS. Suciu, S. SuciuSearch for more papers by this author A. Muresan, A. MuresanSearch for more papers by this authorC. Alb, C. AlbSearch for more papers by this authorD. Daicoviciu, D. DaicoviciuSearch for more papers by this authorA. Filip, A. FilipSearch for more papers by this authorS. Clichici, S. ClichiciSearch for more papers by this authorF. Galea Catoi, F. Galea CatoiSearch for more papers by this authorS. Suciu, S. SuciuSearch for more papers by this author First published: 20 November 2009 https://doi.org/10.1016/S0020-7292(09)62070-1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S577-S578 RelatedInformation

Recent research suggests that oxidative stress plays an important role in the development of gastroduodenal diseases associated with Helicobacter pylori. We investigated the variation of oxidative stress parameters following administration of antiulcer therapy in 79 patients with duodenal ulcer and chronic gastritis respectively, infected with Helicobacter pylori. Serum and tissue oxidative stress parameters were significantly modified in the period between diagnosis and healing of lesions. The results obtained indicated an increased production of oxygen reactive species at both serum and gastric tissue levels in the patients diagnosed with gastro-duodenal peptic disease. The production was directly correlated with the severity of the injury. In parallel a deficit of the physiological production of endogenous antioxidants was found, also correlated with the severity of the injuries. Antiulcer treatment led to the improvement of the antioxidant status, healing of lesions and eradication of the infection; a significant decrease of the pro-oxidant compounds in the blood and in the tissue was also found, especially at the level of the antral gastric tissue; they were more marked in the patients with duodenal ulcer as compared to those with chronic gastritis

Carbon tetrachloride is an organic solvent known fo r its hepatotoxicity. Its effects are due to CCl 3 · radical production. Chitosan is a natural antioxid ant obtained from the exoskeleton of the crustaceous; it protects the liver against the oxidative stress. We used 40 female Wistar rats (weight 230±25 gr.) divided into 4 equal groups. Gr oup I was the control one; Group II received a unique dose of 3 ml/kg CCl 4 by gavage; Group III received daily 5 mg/kg vitami n E i.m. for a week before the CCl 4 administration. Group IV received daily 3 mg/kg ch itosan i.p. for a week before the CCl 4 administration. 24 hours after the CCl 4 have been given, blood and liver tissue samples we re taken. We assessed the oxidative stress markers (ma londialdehyde) and antioxidant defence markers (hydrogen donors' capacity and reduced glutathione) both from serum and liver tissue. CCl 4 acute administration induced oxidative stress especially in the liver tissue (malondialdehyde level increase s, while glutathione level decreased). However, for th e animals that have been protected with chitosan, the oxidative stress markers had almost similar val ues to those of the control group. The histopathological findings confirm the results. The refore, chitosan has a protective effect against li ver injuries induced by acute exposure to CCl 4.

Hypoxia/ischemia and reperfusion is associated to increased production of reactive oxygen species, hence the attempts to use antioxidants compounds in order to combat their deleterious effects. The aim of this study was to evaluate the antioxidant effects of a red grape seed extract in experimental hypobaric hypoxia. Rats were divided in 4 groups: 1 control group and 3 groups exposed for 24 hours to hypobaric hypoxia 5500 m simulated altitude. One of these groups was given grape seed extract before exposure and one group was given immediately after exposure. Oxidative stress parameters and antioxidant enzymes were measured in both plasma and brain homogenate. We found that hypobaric hypoxia exposure inhibits the activity of superoxide dismutase and catalase in brain and increases oxidative stress parameters. Polyphenols do not seem to influence the activity of antioxidant enzymes in the brain.

Non-melanoma skin cancers such as squamous cell carcinoma and basal cell carcinoma are the most common types of human tumors, representing 30% of the new cases of malignancies diagnosed each year. Ultraviolet radiation (UV) from the sun is a major cause of non-melanoma skin cancer in humans. The prevention and mainly the photochemoprevention with natural products represent a simple but very effective strategy in the management of cutaneous neoplasia. Here we review the progress in the research of new and existing agents developed to protect the skin exposed to UV. We also discuss the current state of knowledge on their photosuppression mechanism in humans as well as in animal models, and efficiency in cancer prevention.

UNLABELLEDPorphyrins and new chitosan hydrogels based composites with porphyrins are used as active cytotoxic antitumor agents in photodynamic therapy (PDT).AIMThe present study evaluates the effects of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) and 5-ALA associated with chitosan (CS) using Walker carcinosarcoma in rats as experimental model.METHODSThe animals were irradiated with red light ( lambda = 685 nm, D = 50 J/cm(2), 15 min) 3 h after i.p. administration of 5-ALA (250 mg/kg b.w.) or a mixture of 5-ALA (250 mg/kg b.w.) and CS (1.5 mg/kg b.w.). The animals were sacrificed at 1, 3, 6, 24 h and 14 days after the treatment. The effects of PDT were investigated by morphological studies, monitoring the 5-ALA induced protoporphyrin IX (Pp IX) level in tumor tissue and serum, MMP 2 and 9 (gelatinases) activity in tumor and malondialdehyde level (MDA), marker of the lipoperoxidation process, in tumor and serum.RESULTSZymography revealed an increased activity of MMP 2 in tumors from animals treated with 5-ALA PDT. PDT with 5-ALA induced a higher lipid peroxidation in tumor tissue compared with 5-ALA-CS. CS associated to 5 ALA PDT enhanced the accumulation of PS in tumors inducing earlier necrotic changes. In the same time CS reduced MMP 2 activity.CONCLUSIONOur results suggest that MMPs activation and oxygen reactive species are involved in PDT effects.

In the complex aetio-pathogenesis of gastric ulcer; aggression factors; defence mechanisms and cell-protective factors are involved. Among the aggression factors; the reactive oxygen species can be found as causal agents but especially as factors that aggravate the primary lesions. The authors studied the implications of the oxidant /antioxidant system in acute ulcerations of gastric mucosa; induced by non-steroid anti-inflammatory drugs (indomethacin). An experimental model was realized using Wistar rats that received 50 mg/kg of indomethacin in 5 ml distilled water; through gavage. The gastric lesions were quantified and their histopathologic examinations were performed. From the stomach homogenate; the authors determined the parameters of the oxidative stress (lipid peroxides; free malondialdehyde); the antioxidant capacity (hydrogen donor capacity) and nitric oxide. Significant increases of the oxidative stress parameters and significant decreases of the antioxidant capacity were found. The nitric oxide did not present significant modifications. The administration of indomethacin produced gastric ulcerations in which the oxidative stress is implicated.

The oxidative effects of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) and chitosan (CS) were evaluated in Wistar rats s. c. inoculated with Walker 256 carcinoma. The animals were irradiated with red light (?=685 nm, D=50 J/cm2, 15 min) 3h after i.p administration of 250 mg/kg b.w. 5-ALA, 1.5-mg/kg b.w. CS or an associated treatment of 5-ALA and CS. The levels of lipid peroxides and protein carbonyls were determined in plasma and tumor tissues. The antioxidant capacity of plasma and tumor tissues as well as the antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) activities in erythrocytes and tumors were assessed. 24hs after the treatment, in 5-ALA treated animals the levels of lipid peroxides and protein carbonyls were significantly increased both in plasma and tumors. 5-ALA PDT decreased the erythrocyte antioxidant enzymes activities. An associated treatment with CS and 5-ALA produced the reduction of the lipid peroxides and protein carbonyls in plasma and the recovery of antioxidant enzymes activities. These results suggest the antioxidant properties of CS

We have studied the short-term and long-term effects of a single dose of Dexamethasone upon the nervous system. Studies have been performed with 2 groups of 15 Wistar rats: I (control), 11-2i/g Dexamethasone i.p., during the first 24 hours of life. At 3 days old, we sacrificed 5 animals from each group; the others performed functional tests at 3 months old and then were sacrificed. At 3 days and 3 months old, we explored: the histological disorders, the neuronal viability, the cytochrome oxidase activity, the Mg-dependent ATPase activity from the cerebral cortex, hippocampus and hypothalamus, and oxidative stress parameters from the homogenates. Our results indicate the presence of immediate morphological, enzymatic and oxidative stress disorders in all the brain structures, partially reversible until the age of 3 months.