Celal Güven

Melatonin Prevents Mitochondrial Damage Induced by Doxorubicin in Mouse Fibroblasts Through Ampk-Ppar Gamma-Dependent Mechanisms

Background Doxorubicin (brand name: Adriamycin®) is used to treat solid tissue cancer but it also affects noncancerous tissues. Its mechanism of cytotoxicity is probably related to increased oxidation, mitochondrial dysfunction, and apoptosis. Melatonin is reported to have antiapoptotic and antioxidative effects. The aim of this study was to determine whether melatonin would counteract in vitro cytotoxicity of doxorubicin in mouse fibroblasts and determine the pathway of its action against doxorubicin-induced apoptosis. Material/Methods We measured markers of apoptosis (cytochrome-c, mitochondrial membrane potential, and apoptotic cell number) and oxidative stress (total oxidant and antioxidant status) and calculated oxidant stress index in 4 groups of fibroblasts: controls, melatonin-treated, doxorubicin-treated, and fibroblasts concomittantly treated with a combination of melatonin and doxorubicin. Results Melatonin given with doxorubicin succesfully countered apoptosis generated by doxorubicin alone, which points to its potential as a protective agent against cell death in doxorubicin chemotherapy. This also implies that patients should be receiving doxorubicin treatment when their physiological level of melatonin is at its highest, which is early in the morning. Conclusions This physiological level may not be high enough to overcome doxorubicin-induced oxidative stress, but adjuvant melatonin treatment may improve quality of life. Further research is needed to verify our findings.

The Potential Anti-Diabetic Effects of Some Plant Species

Diabetes mellitus is a global disease, of which prevalence increases rapidly. It causes severe microvascular and macrovascular complications such as retinopathy, nephropathy, cardiomyopathy, neuropathy etc. These contribute to morbidity and mortality in diabetic patients. Therefore, it is important to find an effective therapy method(s) for the protection of body from diabetes-related complications. In this sense, herbal products are of great importance. Herein, this review will highlight the potential usage of some herbals as a preventive and/or therapeutic approach in diabetes and discusses the possible underlying mechanisms of anti-diabetic actions.

Evidence that Extreme Dilutions of Paclitaxel and Docetaxel Alter Gene Expression of In Vitro Breast Cancer Cells

BACKGROUND Gene expression analysis of cells treated with extreme dilutions or micro amounts of drugs has been used to provide useful suggestions about biological responses. However, most of the previous studies were performed on medicines being prepared from a variety of herbal and metal sources. This study investigated the effects of ultramolecular dilution of the taxane anti-cancer drugs, which are not commonly used in homeopathic medicines, on mRNA expression profiles of five key genes (p53, p21, COX-2, TUBB2A and TUBB3) in the breast cancer cell line MCF-7. METHOD MCF-7 cells were exposed to paclitaxel (Taxol) or docetaxel (Taxotere) preparations (6X, 5C and 15C dilutions prepared from pharmacological concentration of 25 nmol/L) for 72 hours. The cell culture groups were evaluated with the trypan blue dye exclusion method for the proliferation/cytotoxicity rates, immuno-staining β-tubulin for microtubule organization, and reverse transcription polymerase chain reaction for gene expression levels.Fold-change in gene expression was determined by the ΔΔCt method. RESULTS The administration of diluted preparations had little or no cytotoxic effect on MCF-7 cells, but altered the expression of genes analyzed with a complex effect. According to the ΔΔCt method with a five-fold expression difference (p < 0.05) as a cut-off level, ultra-high dilutions of paclitaxel and docetaxel showed differential effects on the studied genes with a concentration-independent activity. Furthermore, the dilutions disrupted the microtubule structure of MCF-7 cells, suggesting that they retain their biological activity. CONCLUSION Despite some limitations, our findings demonstrate that gene expression alterations also occur with ultra-high dilutions of taxane drugs.

Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia

Background Myocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress. Material/Methods Rats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia. Blood pressure and electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status (TAS), and creatine kinase-MB (CK-MB). Results Creatine kinase-MB was not different among the groups. Although TAS was not affected by inhibition of Ang-II production, TOS was significantly lower in the CAP and/or AL groups than in the MI/R group. Furthermore, oxidative stress index was significantly attenuated in the CAP and/or AL groups. Captopril significantly increased the duration of VT during ischemia; however, it did not have any effect on the incidence of arrhythmias. During reperfusion periods, aliskiren and its combinations with captopril significantly reduced the incidence of other types of arrhythmias. Captopril alone had no effect on the incidence of arrhythmias, but significantly increased arrhythmias score and durations of arrhythmias during reperfusion. MAP and heart rate did not show changes in any groups during ischemic and reperfusion periods. Conclusions Angiotensin-II production appears to be associated with elevated levels of reactive oxygen species, but Ang-II inhibitions increases arrhythmia, mainly by initiating ventricular ectopic beats.