ABSTRACT
BACKGROUND: Colon cancer affects 1.23 million people worldwide and is the third most common malignant disease in men and the second in women. The only curative treatment is surgical resection, but a significant number of patients develop local recurrence or distant metastases. One of the alternative treatment methods for colon cancer is photodynamic therapy (PDT). In recent years, hypericin (HYP) derived from Hypericum perforatum has been suggested as a strong candidate photosensitizer for PDT. Our interest is focused on the biophysical changes in colon cancer cells in relation to HYP-mediated PDT. RESULTS: In this study, HYP-mediated PDT at 0.04, 0.08 or 0.15 µM HYP concentrations was performed in HT-29 colon adenocarcinoma cells and the Electron Paramagnetic Resonance (EPR) spectra of the spin labeled cells were obtained. Plasma membranes are already heterogeneous structures; the presence of cancer cells increased the heterogeneity and also fluidity of the plasma membranes. Therefore, the obtained spectra were evaluated by EPRSIMC program, which provides the calculation of heterogeneous structures up to four spectral components with different fluidity characteristics. Generally, two motional patterns were obtained from calculations and the number of them increased at the highest concentration. As the order parameters of the most populated components compared, an increase was observed depending on the HYP concentration. However, because of the heterogeneous structure of membrane, the order parameters of the less populated components did not exhibit a regular distribution. CONCLUSION: After HYP-mediated PDT, concentration dependent changes were observed in the domain parameters indicating an increase in the HYP accumulation.
Subject(s)
Adenocarcinoma/drug therapy , Colonic Neoplasms/drug therapy , Electron Spin Resonance Spectroscopy/methods , Perylene/analogs & derivatives , Photochemotherapy , Photosensitizing Agents/therapeutic use , Plant Extracts/therapeutic use , Adenocarcinoma/pathology , Anthracenes , Cell Membrane/drug effects , Colonic Neoplasms/pathology , Computer Simulation , Cyclic N-Oxides/chemistry , HT29 Cells , Humans , Hydrophobic and Hydrophilic Interactions , Hypericum/chemistry , Membrane Fluidity/drug effects , Neoplasm Recurrence, Local/drug therapy , Perylene/metabolism , Perylene/pharmacology , Perylene/therapeutic use , Photosensitizing Agents/metabolism , Photosensitizing Agents/pharmacology , Plant Extracts/metabolism , Plant Extracts/pharmacology , Spin LabelsABSTRACT
The purpose of this study is to determine the effects of low and high dose of carbendazim on the level of certain hormones and endocrine glands (thyroid, parathyroid, adrenal and pituitary glands) of male rats. Carbendazim is a systemic fungicide with activity against a number of plant pathogens. In this study, daily doses of 0, 150, 300 and 600 mg/kg per day carbendazim were applied to male rats by gavage for 15 weeks. At the end of the experiment, T3, T4, TSH, ACTH and GH levels in rat serum were analysed. Thyroid, parathyroid, adrenal and pituitary glands of rats were taken. A significant increase was observed in serum T3 levels of the rats, which were exposed to 300 mg/kg per day carbendazim doses, compared to the serum T3 levels of the control group. There were no differences between the control and carbendazim-treated group of rats regarding serum TSH, T4, ACTH and growth hormone levels. This showed us that carbendazim caused histopathological damages in thyroid, parathyroid and adrenal glands of rats. No changes were observed in pituitary glands of treated rats. These results suggest that a high quantity of subchronic carbendazim exposure affects thyroid, parathyroid and adrenal glands.
Subject(s)
Adrenal Glands/drug effects , Benzimidazoles/toxicity , Carbamates , Hormones/analysis , Parathyroid Glands/drug effects , Pituitary Gland/drug effects , Thyroid Gland/drug effects , Adrenal Glands/pathology , Adrenocorticotropic Hormone/analysis , Air Pollutants/toxicity , Animals , Benzimidazoles/administration & dosage , Body Weight/drug effects , Growth Hormone/analysis , Male , Organ Size/drug effects , Parathyroid Glands/pathology , Radioimmunoassay , Rats , Thyroid Gland/pathology , Thyrotropin/analysis , Thyroxine/analysis , Triiodothyronine/analysisABSTRACT
Carbendazim is a systemic broad-spectrum fungicide controlling a wide range of pathogens. It is also used as a preservative in paint, textile, papermaking and leather industry, as well as a preservative of fruits. In the present study, carbendazim was administered at 0, 150, 300 and 600 mg/kg per day doses orally to male rats (Rattus rattus) for 15 weeks. At the end of the experiment, blood samples, liver and kidney tissues of each animal were taken. Serum enzyme activities, and haematological and biochemical parameters were analysed. In toxicological tests, 600 mg/kg per day doses of carbendazim caused an increase of albumin, glucose, creatinine and cholesterol levels. Also, at the same doses, white blood cell and lymphocyte counts decreased. However, mean cell hemoglobin and mean cell hemoglobin concentrations increased. Histopathological examinations revealed congestion, an enlargement of the sinusoids, an increase in the number of Kupffer cells, mononuclear cell infiltration and hydropic degeneration in the liver. At the highest doses, congestion, mononuclear cell infiltration, tubular degeneration and fibrosis were observed in the kidney tissue. These results indicate that 300 and 600 mg/kg per day carbendazim affected the liver and kidney tissue and caused some changes on haematological and biochemical parameters of rats.
