In contrast to the literature data for Cu and Fe, the concentrations of copper, iron and nickel in cancerous tissue samples are higher than those in the non-cancerous samples. Furthermore, the Ca levels are lower in cancerous tissue samples than in non-cancerous tissue samples.

In this study, the possible toxic effects of Alternariol Methyl Ether (AME) and Tenuazonic Acid (TeA) produced by Alternaria species on esophagu s of mice were investigated by using light and electron microscopy techniques. Mice were orally fed daily with AME or TeA for 10 months and at the end of this period, the effects of these chemicals on the esophagea l mucosa were determined. By light microscopi c examination, moderate and severe dysplasia characterized by loss of polarity, nuclear pleomorphism , and hyperchromasi a were observed in TeA-treated animals. Electron-microscopi c examination of TeA-treated mucosal epithelial cells revealed pyknosis in some nuclei, granulation and increase in chromatin mass, irregularities in the nuclear contours, vacuolization in nucleoplasms , and marked pleomorphism in the nuclei. In conclusion, our results suggested that TeA has higher toxicity as evidenced by dysplastic transformation.

Our aim was to examine the effects of melatonin on the testicular tissue of adult rats with experimentally-induced left varicocele, and to determine the relationship between melatonin and apoptosis regular proteins in the anti-oxidant defence system. Forty adult male Wistar rats were divided equally into four groups. A sham operation was performed on the rats in group I, and experimental left varicocele was created in groups II, III and IV. Melatonin was administered intraperitoneally at doses of 5 mg/kg and 10 mg/kg to rats in groups III and IV, respectively. An immunohistochemical analysis of the left testicular tissue was performed to evaluate the expression of Bax and Bcl-2, while tissue malondialdehyde (MDA) and antioxidant enzyme activities were assessed in homogenates to determine the role of the oxygen defence system. The immunohistochemical analysis revealed an increased ratio of pro-apoptotic protein Bax in groups II and III, whereas no significant activity was observed in the sham operated rats ( P<0.05). Similarly, the tissue MDA level increased and a significantly decreased level of antioxidant enzymes was observed in these groups ( P<0.05). Although rats in group IV showed a slightly increased ratio of the pro-apoptotic marker Bax, there was no significant difference between groups I and IV. Similarly, group IV showed decreased levels of MDA and increased levels of anti-oxidant enzyme activity with decreased Bax expression. The close relationship between pro-apoptotic/anti-apoptotic markers, reactive oxygen species and antioxidant agents provided a useful in vivo model for studying the pathophysiology of varicocele and evaluating the role of antioxidants in the prevention testicular damage.

The aim of this study was to examine the protective effects of melatonin against CCl4-induced hepatotoxicity in the rat. Twenty-four male Wistar rats were divided into three groups. Group I was used as a control. Rats in group II were injected every other day with CCl4 for 1 month, whereas rats in group III were injected every other day with CCl4 and melatonin for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and conjugated bilirubin levels were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All serum biochemical parameters were significantly higher in animals treated with CCl4 than in the controls. When rats injected with CCl4 were treated with melatonin, significantly reduced elevations in serum biochemical parameters were found. In liver sections of the CCl4-injected group, necrosis, fibrosis, mononuclear cell infiltration, haemorrhage, fatty degeneration and formation of regenerative nodules were observed. Additionally, apoptotic figures, microvesicular steatosis and hydropic degeneration in hepatocytes were seen in this group. In contrast, the histopathological changes observed after administration of CCl4 were lost from rats treated with CCl4 and melatonin. Except for mild hydropic degeneration of the hepatocytes, a normal lobular appearance was seen in the livers of this group. The results of our study indicate that melatonin treatment prevents CCl4-induced liver damage in rats.

Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC 4 , D 4 and E 4 ) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.

Objective: To investigate etiological role of Epstein-Barr virus (EBV) DNA in breast cancer. Materials and Methods: The presence of EBV DNA in 57 breast cancer tissues was investigated with a sensitive PCR assay. The breast cancer tissues were from invasive ductular (n = 28), lobular (n = 20) and other miscellaneous carcinomas (n = 9). Tissues from normal breasts and patients with various benign breast diseases (n = 55): fibrocystic disease (n = 34), fibroadenoma (n = 16), hyperplasia, and granulomatous mastitis (n = 5), were used as control samples. Results: EBV DNA was detected in 13 (23%) cancerous tissues (7 ductular, 4 lobular, 2 other carcinoma) and 19 (35%) in the control tissues. The difference between EBV presence in malignant and benign tissues was not statistically significant (p > 0.05). Conclusion: The presence of EBV DNA was detected almost equally in both breast cancer and normal tissues, which indicates no etiological role for EBV in breast cancer. We suggest further etiological studies.

Melatonin, the principal secretory product of the pineal gland, functions as a potent antioxidant and free radical scavenger. Additionally, the antiapoptotic effect of melatonin has been observed both in vivo and in vitro. The aim of this experimental study was to investigate the protective effects of melatonin against carbon tetrachloride (CCl(4))-induced apoptosis and oxidative stress in rat liver. Twenty-four male Wistar rats were divided in three equal groups. Group I was used as control. Rats in group II were injected every other day with CCl(4) (0.5A mL/kg BW) for a month, whereas rats in group III were treated every other day with the same dose of CCl(4) plus melatonin (25A mg/kg BW). At the end of the experiment, all animals were killed by decapitation and the livers were rapidly removed. Some of the liver tissue specimens were used for determination of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. The remaining tissue specimens were processed for immunohistochemical assessment, and the percentage rates of apoptotic liver cells stained with immunoreactive Bax were determined. Chronic administration of CCl(4) significantly increased liver MDA contents, as an end product of lipid peroxidation, and also significantly decreased SOD and GSH-Px activities, emphasizing the generation of increased oxidative stress. Moreover, it caused an evident increase in apoptotic cells. Melatonin treatment significantly reduced MDA levels and elevated SOD and GSH-Px activities in rats received CCl(4) plus melatonin. Furthermore, apoptotic changes caused by CCl(4) were considerably decreased in these animals. The results of the present study indicate that melatonin treatment substantially prevents CCl(4)-induced apoptosis and oxidative damage in the liver. Thus, melatonin may serve as a drug for treating many clinical conditions that arise from inappropriate apoptosis.

In this study we investigated whether the increase of hepatic vitamin E content by intraperitoneal administration, influences chronic liver damage induced by carbon tetrachloride (CCl(4)) in rats. Thirty adult male Wistar rats were divided into three groups. The first group was used as a control and the rats in the second group were administered CCl(4) in olive oil subcutaneously. Rats in the third group were administered intraperitoneally vitamin E (dl-alpha-tocopherol acetate, 100 mg kg(-1)). This administration was performed three times per week for five weeks. Liver samples were used for the determination of vitamin E levels, glutathione peroxidase (GSHPx) activities and histological examination. Serum levels of alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyltranspeptidase, total and conjugated bilirubin were significantly (p<0.05, p<0.01, p<0.001) higher in animals treated with CCl(4) than in the controls and had returned to normal values by the administration of vitamin E + CCl(4 ). Liver vitamin E levels were significantly (p<0.05) lower in the CCl(4) group than in the control group. However, the liver vitamin E content was significantly (p<0.01, p<0.001) increased in the vitamin E + CCl(4) injected group. On the other hand, liver GSHPx activity was not statistically different among the groups. On histological examination, vitamin E administered animals showed incomplete, but significant, prevention of liver necrosis and cirrhosis induced by CCl(4 ). these data indicate that intraperitoneally administered vitamin E has protective effects against CCl(4)-induced chronic liver damage and cirrhosis as evidenced by biochemical data and conventional histological examination.