Photochemoprevention of cutaneous neoplasia through natural products

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 preventio

Iodide excess exerts oxidative stress in some target tissues of the thyroid hormones

Environmental iodine deficiency continues to be a significant public health problem worldwide. On the other hand, iodide excess results principally from the use of iodine -containing medicinal preparations or radiographic contrast media. For this reason we intended to explore iodide excess impairment on prooxidant/antioxidant balance of the thyroid gland, hepatic tissue and in blood and the effect of selenium administration on oxidative stress markers under the same circumstances. Experiments were performed for 10 days with white, male, Wistar rats, as follows: group 1: control -normal iodine supply group; 2: high iodine diet, group; 3: high iodine diet and selenium; group 4: high iodine diet and Carbimasole. Oxidative stress markers such as lipid peroxides were determined in thyroid gland, hepatic tissue and in blood. Measuring H+ donor ability of the sera and catalase activity in thyroid gland and in hepatic tissue assessed antioxidant defense. Iodide excess had prooxidant effects, leading to an increased lipid peroxides level and catalase activity in target tissues and in blood and to a decreased H+ donor ability of the sera. Selenium supplementation had opposite effects. Present data allow us to conclude that the alterations due to iodide excess in thyroid gland, hepatic tissue and in blood are mediated through oxidative stress

Efects of PDT with 5-aminolevulinic acid and chitosan on Walker carcinosarcoma

Porphyrins and new chitosan hydrogels based composites with porphyrins are used as active cytotoxic antitumor agents in photodynamic therapy (PDT). Aim: The 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. Methods: The animals were irradiated with red light (l = 685 nm, D = 50 J/cm2, 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. Results: Zymography 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. Conclusion: Our results suggest that MMPs activation and oxygen reactive species are involved in PDT effects.Порфирины и новые соединения, основу которых составляют гидрогели хитозана с порфиринами, используются как активные цитотоксические противоопухолевые препараты при фотодинамической терапии (PDT). Цель: оценить действие PDT с 5-аминолевуленовой кислотой (5-ALA) и 5-ALA, ассоциированной с хитозаном (CS), на клетки карциносаркомы Уокера. Методы: крыс облучали красным светом (λ = 685 нм, D = 50 Дж/см2 , 15 мин) 3 ч после внутрибрюшинного введения 5-ALA (250 мг/кг) или смеси 5-ALA (250 мг/кг) и CS (1,5 мг/кг). Подопытных животных забивали через 1 ч, 3 ч, 6 ч, 24 ч и 14 дней после воздействия PDT. Эффект PDT определяли с помощью морфологических исследований, регистрируя уровень протопорфирина IX (Pp IX), вызываемого 5-ALA, в опухолевой ткани и сыворотке крови, активность MMP 2 и 9 (желатиназы) в опухоли и уровень малонового диальдегида (MDA), маркера процесса перекисного окисления липидов, в опухоли и сыворотке крови. Результаты: зимографические исследования показали повышенную активность MMP 2 в опухолях животных, которых подвергали 5-ALA PDT. PDT с 5-ALA вызывала повышенный уровень перекисного окисления липидов в опухолевой ткани по сравнению с 5-ALA-CS. CS с 5 ALA PDT усиливал накопление фотосенсибилизирующего вещества (PS) в опухолях, вызывая более ранние некротические изменения. В то же время CS снижал активность MMP 2. Выводы: полученные результаты позволяют предположить, что для проявления эффектов PDT необходимы активация MMP и образование активных форм кислорода

Studies on antioxidant effects of the red grapes seed extract from Vitis Vinifera, Burgund Mare, Recaş in pregnant rats

To estimate the effects of hydroethanolic red grapes seeds extract obtained from Vitis vinifera, Burgund Mare variety, Recaş , Romania (BMR) on oxidant-antioxidant ballance, as compared to ascorbic acid, during pregnancy in rats. Thirty Wistar female rats were assigned to three groups (n=10) which were administered by gavage: Group I, 3 × 100 mg/kg body weight saline, Group II — BMR 3 × 30 mg gallic acid equivalents/kg body weight; Group III — vitamin C 3 × 100 mg/kg body weight on days 1, 7 and 14 of pregnancy. On day 21 blood samples were collected. Malon dyaldehyde, lipid peroxides, protein carbonyls, nitric oxide (as oxidative stress parameters) and hydrogen donor ability and total thiol groups (as antioxidant parameters) serum concentrations were measured. Vitamin C significantly enhanced the antioxidant capacity of plasma (hydrogen donor ability, p=0.0001; thiol groups, p=0.0001), as well as nitric oxide levels (p=0.001). The extract increased the plasma antioxidant capacity (hydrogen donor ability, p=0.001; thiol groups p=0.001) and did not elevate the nitric oxide plasma levels in pregnant rats.In conclusion, in the chosen dose, the red grapes seed extract enhanced the plasma antioxidant capacity and did not influence the nitric oxide levels in pregnant rats

Implications of oxidative stress mechanisms in toxicity of nanoparticles (review)

Nanosized particles (NPs) have recently been proposed for extensive use, including into the biomedical field. As a result, research on toxicity and oxidative stress concerning the interaction of nanoparticle and the living organism has attracted increasing interest among specialists. Two different targets have been the motor of this type of research: 1) the safety concern regarding such NPs large-scale use along with the need to generate antidote solutions to possible adverse effects, 2) the idea of influencing oxidative damage and of using them for elaborating anticancer/antimicrobial therapies. Present study reviews recent research achievements within the proposed theme taking into account the nature and particularities of each type of nanoparticle

The dynamics of reactive oxygen species in photodynamic therapy with tetra sulfophenyl-porphyrin

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-tetrasulfophenyl-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

The effects of chitosan and low dose dexamethasone on extrahepatic cholestasis after bile duct ligation in Wistar rats

Inflammation and oxidative stress are important pathways in the development of liver fibrosis following biliary obstruction.Aim: To evaluate the effects of low dose dexamethasone and chitosan, a natural compound with no side-effects, on liver damage caused by bile duct ligation in rats.Materials and methods: Fifty female Wistar rats, randomly and equally divided in 5 groups: I (SHAM) underwent only laparotomy, II (BDL) with bile duct ligation, III (DEX) 0.125 mg/kg dexamethasone i.m. daily, IV (CS) 1 mg/kg chitosan by gavage and group V (DEX+CS), both substances. After six days, the following parameters were assessed from liver homogenates: malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), total SH groupings, nitric oxide (NO), and from plasma: MDA, γ-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB). A histopathological examination was performed using some of the elements of the Knodell Histological Activity Index.Results: BDL significantly increases the levels of MDA, liver enzymes, and the necro-inflammatory score compared to the sham group and it decreases the antioxidant capacity. DEX protects against lipid peroxidation and improves the antioxidant capacity, but it is not able to protect the hepatocytes. Chitosan significantly decreases (p<0.05) the levels of MDA (0.07±0.01 vs 0.10±0.01 nmoles/mg protein BDL group, p=0.027) and also ALT, TB, GGT and reduces liver necrosis and inflammation (2.75±0.95 vs 1±0, p<0.05). Both CS and DEX reduce the level of NO significantly.Conclusion: BDL induces severe oxidative stress damage after six days already. Chitosan proved very efficient in protecting the hepatocytes against oxidative stress, a fact supported by the histological findings