Gamma radiation is known to cause serious damage in the brain, and many agents have been used for neuroprotection. In this study, lipid peroxidation levels and histopathological changes in brain tissues of whole-body irradiated rats with likely radiation injury were compared to those with melatonin and vitamin E protection. Forty rats in four equal groups were used. The control group received neither radiation nor medication. The remaining groups received doses of 720 cGy in two equal fractions 12 h apart. The second group received radiation but no medication, the third received radiation plus 100 mg/kg per day of vitamin E i.p., and the fourth received radiation plus 100 mg/kg per day of melatonin i.p. over 5 days. On the 10th postoperative day, all the rats were decapitated and specimens from parietal cortices were analyzed for tissue malondialdehyde (MDA) levels and histopathological changes. Increases in MDA were relatively well prevented by melatonin treatment but less so with vitamin E therapy. On histopathological examination, melatonin significantly reduced the rates of edema, necrosis, and neuronal degeneration, whereas vitamin E reduced only necrosis. Neither substance was capable of preventing vasodilatation. In conclusion, melatonin may be useful in preventing the pathological changes of secondary brain damage as a result of free oxygen radicals generated by irradiation.

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Conditioning regimens used during stem cell transplant provide prolonged control or cure of the disease in patients with acute lymphoblastic leukemia (ALL). In this study, we present a comparison of treatment results for 95 patients with ALL who underwent allogeneic hematopoietic stem cell transplant (AHSCT) with total body irradiation plus cyclophosphamide (TBI + Cy) or busulfan plus cyclophosphamide (Bu + Cy) as conditioning regimen. Median age was 25 (range: 9-54) years. Median follow-up was 24 (range: 3-107) months. Median overall survival (OS) was found to be 29 months. Median event-free survival (EFS) was 9 months. Median OS was 37 months in the TBI + Cy arm, while it was 12 months in the Bu + Cy arm, suggesting a significant advantage favoring the TBI + Cy arm (p = 0.003). Median EFS was 13 months in the TBI + Cy arm, while it was 4 months in the Bu + Cy arm, indicating a significant difference (p = 0.006). In univariate and multivariate analysis, it was found that high OS and EFS were significantly correlated with TBI + Cy conditioning regimen and lack of transplant-related mortality (p < 0.05). The TBI + Cy conditioning regimen was found to be superior to the Bu + Cy regimen in patients with ALL undergoing AHSCT regarding both OS and EFS.

Clin Invest Med 2008; 31 (5): E242-E247. AbstractPurpose: The prevention of radiation-induced pulmonary toxicity may help to improve radiation therapy in the cancer patient. The aim of this study was to investigate the pulmonary protective effects of caffeic acid phenethyl ester (CAPE), an antioxidant, on radiation-induced lung injury in rats. Methods:30 Wistar albino rats were divided into three groups and treated with saline, Radiation (RT) and RT + CAPE respectively. All rats were treated with CAPE (50 μmol/kg i.p.) or saline. The first dose of CAPE was injected 24 h before radiation and application continued daily, with radiation in second day and 2 days more after the radiation treatment. Radiation dose was 800 cGy for total body. At 72 hr after the last radiation application, under general anesthesia using ip ketamine, the lungs were removed immediately after decapitation. After sacrification, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) activities and malondiadehyde (MDA) levels were evaluated in lung tissue. Results: The level of malondialdehyde (MDA) was higher in the RT group (233.4±1.5 nmol/g protein) than in both the control (131.8±0.92) and the RT + CAPE (151.4±1.8) groups (P < 0.001). However, CAT activity was decreased in the RT group (7.26±0.27 Umg protein) compared with control (8.49±0.51) and increased again in the RT + CAPE group (8.31±0.56; P<0.001). In accord with CAT activity, SOD activity in the RT group (0.42±0.07 nmolMDA/g wet tissue) was different from the control (0.78±0.02) and RT + CAPE (0.86±0.06) groups (P< 0.001). Conclusion: CAPE aplication with radiation therapy attenuated radiation induced pulmonary injury in vivo, possibly by its antioxidant effect.When radiation is absorbed by a biological material, free oxygen radicals are produced. The radicals are highly reactive molecules and, via chemical bonds that produce chemical changes, initiate a chain of events that result in biological damage. They can be produced either directly in the target molecule (usually DNA) or indirectly in other cellular molecules and they diffuse far enough to reach and damage critical targets. Most indirect effects occur by free radicals produced in water, since water makes up 70-80 % of mammalian cells. 1 In this way, chemotherapy and radiotherapy eliminate cancer cells, but their nonspecific targeting also destroys normal, healthy cells, particularly in epithelial tissues. Damage to the epithelium of the respiratory tract results in a pathologic condition known as pneumonitis . 2 Radiation (RT) is frequently used to treat tumors in and around the thorax. In these patients, RT-induced lung injury is common, occurring in 5% to 20% of patients with lung cancer. The incidence is somewhat less, 5% to 15%, for patients with tumors such as mediastinal lymphoma and breast cancer . 3 ORIGINAL RESEARCH

Clin Invest Med 2008; 31 (4): E182-E188.Abstract Purpose: To investigate the possible protective effects of aminoguanidine (AG ) on lung damage in whole body irradiated rats. Methods: To evaluate the biological damage of radiation on rat lung tissue, lipid peroxidation products were measured using biochemical parameters. Thirty Wistar albino rats were divided into three subgroups: control (C) , irradiation alone (RT), and RT + AG combined. After sacrificing the rats, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities and malondiadehyde (MDA), nitric oxide (NO) levels were evaluated in lung tissue. Results: Administration of AG resulted in an increase in the activities of CAT, SOD and GSHPx in the lungs. All were reduced after radiatio. In addition, AG administration resulted in a decrease in both NO and MDA levels in lung compared with the irradiated group. Conclusion: Amnoguanidine increased the endogenous antioxidant defence mechanism in rats and protected the animals from radiation-induced lung toxicity. Moreover, AG may protect against ionizing radiation-induced lung damage because of its antioxidant effect.Radiation therapy (RT) is a crucial component of application for many thoracic malignancies. Radiationinduced lung toxicity remains a major factor that limits the ability to escalate radiation doses in the application of thoracic tumours. RT-related pulmonary symptoms occur in up to 30% of patients irradiated for lung cancer, breast cancer, lymphoma, or thymoma. Pulmonary toxicity from thoracic irradiation is also an important problem in other settings, including combined modality treatment of Hodgkin's disease and esophageal cancer, and bone marrow transplantation with total body irradiation. 1 Ionizing radiation is a well-established carcinogen due to the resulting oxidative damage, and the molecule most often reported to be damaged by this physical agent is DNA. 2 Aproximately 60-70% of cellular DNA damage produced by ionizing radiation is caused by OH, formed from the radiolysis of water. 3 Besides DNA, lipids and proteins are also attacked by free radicals induced by ionizing radiation. 4 Lipid peroxidation is believed to be an important cause of destruction and damage to cell membranes and has been suggested to be a contributing factor to the development of oxygen radicals-mediated tissue damage. 5 Oxidative stress occurs when there is excessive free radical production and/or low antioxidant defence, and results in chemical alterations of biomolecules causing structural and functional ORIGINAL RESEARCH