Ruksan Cehreli

Toxicity Induced by he Chemical Carcinogen 7,12-Dimethylbenz[a]anthracene and the Protective Effects of Selenium in Wistar Rats

7,12-Dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention. On the other hand, selenium (Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties. Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification. In this study, rats were administered a single, oral dose of DMBA (12 mg). In the Se group, rats received 20 µg Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk. One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria. Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA–Se-treated group. Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the DMBA–Se-treated group. Some inflammatory changes rather than epithelial changes were found upon histopathological examination. GPx activity and blood urea nitrogen levels were higher and kidney GST activity was lower in the DMBA–Se-treated group compared to DMBA alone. In conclusion, Se appears to be effective in preventing some of the adverse effects associated with DMBA. This research has been partially carried out at Dokuz Eylul University School of Medicine, Learning Resources Center Research Laboratory (ARLAB). The authors thank Dr. Ali Riza Sisman for his kind contributions and Prof. Dr. Gul Guner and Dr. Sam Kacew for their helpful advice.

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

Background Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells. Methods Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549) and p53-null (H1299) cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels. Results Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50) values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 μM and 100 μM. Conclusion Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells.

Does Antioxidant Supplementation Alter the Effects of Acute Exercise on Erythrocyte Aggregation, Deformability and Endothelium Adhesion in Untrained Rats?

This study aimed to determine whether high-dose antioxidant supplementation had an impact on the acute exercise effects related to erythrocyte membrane mechanics. Experimental animals (n=32) were divided into four groups as control, exercised, supplemented, and supplemented + exercise. Four-week antioxidant supplementation (vitamin C, vitamin E, and zinc) was applied to experimental animals. Following acute exercise on a motor-driven rodent treadmill, erythrocyte aggregation and deformability, erythrocyte adhesion to endothelial cells, superoxide dismutase (SOD), and glutathione peroxidase activities of the erythrocytes were analyzed. In both supplemented and non-supplemented exercised groups, there was a significant decrease in SOD activities and erythrocyte aggregation, and an increase in adhesion to endothelial cell although there was no change on erythrocyte deformability. There were no differences in the responses to the exercise of supplemented and nonsupplemented rats. The data suggested that high-dose antioxidant supplementation did not alter the effects of acute exercise on erythrocyte membrane mechanics.

New paraneoplastic syndrome in chronic basophilic leukemia

Chronic basophilic leukemia (CBL) is an extremely rare disorder. A female patient presented with recurrent attacks of chills, fever and abdominal pain was found to have simultaneous cyclic oscillation in leukocyte counts and C-reactive protein values. She was initially diagnosed with familial Mediterranean fever and treated with colchicine. Diagnosis of CBL was established by morphologic studies of peripheral blood and bone marrow. Her febrile attacks recurred with marked elevation in serum interleukin-6 (IL-6) level when basophil counts climbed to peak levels during cyclic oscillation. Molecular studies by real-time PCR showed IL-6 gene expression in neoplastic basophils separated by magnetic-activated cell sorting infiltrating the bone marrow, suggesting that IL-6 is released by neoplastic basophils of an underlying CBL, resulting in a new paraneoplastic syndrome that mimics autoinflammatory disorders.

Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis

Background The aim of the study was to investigate preventive effects of glutamine (Gln), omega-3 fatty acids (FA) on erythrocyte deformability (EDEF) in rat model of indomethacin-induced enterocolitis. Methods Nineteen Wistar albino male rats were divided into three groups: control group, colitis induced by indomethacin and were fed with a standard laboratory diet (group 1), and colitis induced by indomethacin and were also fed with Gln, omega-3 FA (group 2). An investigation was performed in a rat model of experimental colitis induced by subcutaneous injections of 2 mL intdomethacine solution applied at 24 and 48 hours intervals to male Wistar rats for 14 days. Gln and omega-3 FA were added to the daily standard diets of the animals during 14 days of injections. During the study, changes in body weight were evaluated. The intestines were examined, and colitis was macroscopic and histologically scored. The circulating tumor necrosis factor alpha (TNF-α) and interleukine-1β (IL-1β), erythrocyte transit time (ETT) and thiobarbituric acid reactive substances (TBARS) levels were determined in addition to calculation of EDEF indices in all groups. Results No significant differences in body weight changes could be determined between the standard diet and special diet groups at the end of the experiment. After macroscopic and microscopic scoring, in all of the groups that colitis was found induced, the lowest microscopic score was observed in the group 2. But Gln and omega-3 FA supplemented diet did not change the mean macroscopic and histological scores in all rats. The proliferating cell nuclear antigen (PCNA) levels were significantly higher in group 1 and group 2 compared to the control group. Effects of the diet on circulating TNF-α and IL-1β levels were found correlated with inflammation but statistically significant differences were not found in the group 1 and group 2 (P < 0.05). The ETT and TBARS levels in standard and special diet groups were significantly increased (P < 0.05). However, EDEF indices which are an important parameter of the study were decreased in indomethacin-induced enterocolitis groups that fed with standard and special diet. Conclusions Increases in ETT and TBARS levels did not return to normal by addition of Gln and omega-3 FA to diet. Our results suggest that determination of effective optimal doses and route of administration for these nutrients may play an important role in reducing EDEF and microvascular changes.

The effects of parenteral glutamine on intestinal adaptation in a rat model of short bowel syndrome

Short bowel syndrome (SBS) is characterized by the malabsorption of nutrients and fluids that occurs after major intestinal resection, resulting from an adaptation process that begins immediately to increase the mucosal surface area and absorption. Certain nutrients and trophic factors are widely used to increase intestinal adaptation following massive intestinal resection. The efficacy and benefits of glutamine on the intestinal adaptation process is still controversial. This study was conducted to determine the effects of parenteral glutamine administration on intestinal adaptation in a rat model of SBS. Fourteen male Wistar rats were divided into two groups; all 14 underwent 75% small bowel resection. Within each group, rats were assigned to 14 days of treatment with subcutaneous glutamine (0.3 g/kg/day) or isotonic saline daily. Weight changes and histological intestinal adaptation parameters (mucosal thickness, villus height, and crypt depth) were measured. Non-mucosal intestinal changes were evaluated by intestinal fractioned collagen analysis. All rats initially lost weight and began to gain weight postoperatively; however, they did not reach their preoperative weights during the experiment and there was no significant difference between the groups. Histological adaptation parameters were significantly increased after 75% intestinal resection in both groups compared to paired native samples (P<0.01); although the percent of increase was slightly higher in Gln group, no significant difference was detected between the two groups. Fractioned-collagen amounts were found to be similar between groups. The results indicated that parenteral glutamine administration alone does not improve the intestinal adaptation process after massive intestinal resection in rats.