High-dose testosterone and dehydroepiandrosterone induce cardiotoxicity in rats: Assessment of echocardiographic, morphologic, and oxidative stress parameters.

The aim of this study is to assess cardiotoxic effect of testosterone (TES) and dehydroepiandrosterone (DHEA) in Sprague Dawley rats. We compared the impact of subacute (14 days) and subchronic (90 days) administration of suprapharmacologic doses of TES and DHEA on body weight, locomotor activity, muscle strength, echocardiographic parameters, heart histopathology, and oxidative stress markers with the control group. Testosterone (10, 30, and 100 mg/100 g body weight) and DHEA (10 mg/100 g body weight) administration decreased the body weights and locomotor activity (p < 0.05), and the combination of both increased muscle strength (p < 0.05) in rats. In our histopathological evaluation, misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in high-dose TES (100 mg/100 g)-treated rats, especially on day 14. On day 90, mild changes such as misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in TES and DHEA-treated groups. According to our echocardiographic study on day 14 and day 90, TES, especially at high doses, induced increase in left ventricular posterior wall diameter and ejection fraction (p < 0.05). In this study, blood oxidative stress marker malondialdehyde was increased slightly but not significantly in TES and DHEA groups. On the other hand, antioxidant enzymes such as SOD and glutathione peroxidase (GSH-Px) levels were slightly but not significantly increased in TES and DHEA groups. These data demonstrate that the potential risk to cardiac health due to exogenous androgen use may be related to oxidative stress in rats.

The relation between oxidative stress, inflammation, and neopterin in the paraquat-induced lung toxicity.

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon γ and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1ß (TGF-1ß) levels were significantly higher than the sham group (in all, p < 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p = 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1ß levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation.

Cyclophosphamide (CP) and ifosfamide (IF) are widely used antineoplastic agents, but their side-effect of hemorrhagic cystitis (HC) is still encountered as an important problem. Acrolein is the main molecule responsible of this side-effect and mesna (2-mercaptoethane sulfonate) is the commonly used preventive agent. Mesna binds acrolein and prevent its direct contact with uroepithelium. Current knowledge provides information about the pathophysiological mechanism of HC: several transcription factors and cytokines, free radicals and non-radical reactive molecules, as well as poly(adenosine diphosphate-ribose) polymerase (PARP) activation are now known to take part in its pathogenesis. There is no doubt that HC is an inflammatory process, including when caused by CP. Thus, many cytokines such as tumor necrosis factor (TNF) and the interleukin (IL) family and transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) also play a role in its pathogenesis. When these molecular factors are taken into account, pathogenesis of CP-induced bladder toxicity can be summarized in three steps: (1) acrolein rapidly enters into the uroepithelial cells; (2) it then activates intracellular reactive oxygen species and nitric oxide production (directly or through NF-kappaB and AP-1) leading to peroxynitrite production; (3) finally, the increased peroxynitrite level damages lipids (lipid peroxidation), proteins (protein oxidation) and DNA (strand breaks) leading to activation of PARP, a DNA repair enzyme. DNA damage causes PARP overactivation, resulting in the depletion of oxidized nicotinamide-adenine dinucleotide and adenosine triphosphate, and consequently in necrotic cell death. For more effective prevention against HC, all pathophysiological mechanisms must be taken into consideration.

Melatonin seems to be a mediator that transfers the environmental stimuli to oocytes for inheritance of adaptive changes through epigenetic inheritance system.

Possibility of inheritance of epigenetic modifications have led us to consider that adaptive geographic variations in humans may result from interactions between environmental factors and epigenetic inheritance system. In this system melatonin seems to be a mediator that transfers the environmental stimuli to germ cells (oocytes). While environmental factors produce modifications in the body, they simultaneously induce epigenetic modifications in the oocytes with the help of melatonin, and these changes are inherited to offspring. In this way, adaptive changes could be passed on to the next generation. This kind of heritable long-term changes is generally labeled biological adaptation. But, how can melatonin cause epigenetic changes in oocytes? We suggest that melatonin induces epigenetic modifications by affecting the nuclear melatonin receptors that can in turn change the superstructure of DNA. It was previously suggested that biological adaptation is limited to neural crest derivatives such as, craniofacial tissues, melanocytes, and structures related to stature, hair form and body proportions. Thus, inheritance of adaptive changes is possible only where environmental factors affect the neural crest derivatives, including the cells that produce the next generation.

Hyperbaric oxygen treatment time for cyclophosphamide induced cystitis in rats.

The aim of this study was to evaluate the prophylactic potential of hyperbaric oxygenation treatment and the timing of hyperbaric oxygen (HBO2) therapy for cyclophosphamide-(CYP) induced cystitis in rats. Forty male Sprague-Dawley rats were divided into 5 groups. Four groups received a single dose of CYP (100 mg/kg.) intraperitoneally (i.p.) at the same time (group 1 served as the control). Group 2 received CYP only; group 3 received HBO2 treatment (2.8 atmospheres absolute, 90 minutes, twice daily) before and the day after CYP. Group 4 received HBO2 before and on the day of CYP administration. Group 5 received HBO2 on the day of and the day after CYP. CYP injection resulted in severe cystitis. Prophylactic HBO2 treatment did not prevent the severe cystitis. After CYP injection, however, HBO2 treatment attenuated CYP-induced hemorrhagic cystitis in rats. Hyperbaric oxygen has a beneficial effect on repairing and healing bladder damage, though it does not function to prevent CYP-induced hemorrhagic cystitis.

The prevalence of allergic diseases in primary school children in Edirne, Turkey.

BACKGROUND: Allergic diseases present a major health burden for children as shown by the rising morbidity and increased mortality from asthma. Information on the prevalences of allergic disorders and contributing factors as well will help to establish feasible measures to change this trend, and more efficient assignment of the limited health resources. OBJECTIVE: To assess the prevalences of asthma and other allergic diseases and the contribution of various risk factors in primary school children in Edirne, Turkey. METHODS: Children aged 7 to 12 in primary schools in the municipality and 24 villages of Edirne were surveyed via a questionnaire completed by the parents. The cumulative (lifetime) and current (last 12 months) prevalences of allergic diseases and the presence of passive smoking, atopic family history, animal contact and breast-feeding in infancy were determined. RESULTS: A total of 5412 children (70.1% from the metropolitan and 29.9% from the rural area) were enrolled. The cumulative and current prevalences of all allergic diseases were 24.6% and 9.9% respectively. The cumulative (lifetime) prevalences of bronchial asthma, wheezing, allergic rhinitis and atopic dermatitis were 16.4%, 18.9%, 12.3% and 2.2%, and the current (last 12 months) prevalences were 5.6%, 5.8%, 4.5% and 0.9% respectively. Three-fourths of the children were exposed to tobacco smoke at home. Atopic heredity appeared the most prominent risk factor for any allergic disorder. Neither age, breast-feeding nor place of habitation affected the occurrence of allergic disorders. Animal contact was a significant risk factor for asthma and wheezing (adjusted odd ratios (OR) and 95% confidence intervals (CI) for current prevalences are 1.38 (CI = 1.04-1.83) and 1.35 (CI = 1.02-1.78) respectively), exposure to indoor tobacco smoke for wheezing (OR = 1.52, CI = 1.10-2.09), and male gender for asthma (OR = 1.50, CI = 1.16-1.93). Current prevalences for all allergic diseases were significantly lower than those previously reported in Ankara, Turkey. CONCLUSIONS: Allergic diseases are a major health burden for primary school children in Edirne, Turkey. Although atopic heredity appears to be the foremost important risk factor, reduction of exposure to indoor tobacco smoke and animal contact, especially for those with atopic family history, are important preventive measures. The impact of environmental exposures on distinguishing prevalences of allergic diseases in Ankara and Edirne should be further investigated.