Impact of Radiation Therapy on Serum Humanin and MOTS-c Levels in Patients with Lung or Breast Cancer.

BACKGROUND: Lung and breast cancer are the most frequent causes of death from cancer globally. The objectives of this research were to evaluate the serum mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) and humanin levels in lung or breast cancer patients, and investigate the impacts of radiation therapy on the circulating levels of these peptides. METHODS: 35 lung cancer patients, 34 breast cancer patients, and healthy volunteers as a control group were recruited in this prospective observatory research. Lung cancer patients with stage IIIA/IIIB were treated with paclitaxel-based chemotherapy plus radiotherapy (2 Gy per day, 30 times, 60 Gy total dose). Breast cancer stage IIA/IIB patients were treated with postoperative locoregional radiation therapy (2 Gy per day, 25 times, 50 Gy total dose). The ELISA method was used to detect serum humanin and MOTS-c levels during, before, and after radiotherapy. RESULTS: We observed marked elevations in circulating MOTS-c, but not humanin levels in patients with lung cancer (P < 0.001). Radiation therapy led to a marked augmentation in MOTS-c levels in these patients (P < 0.001). On the other hand, there was a marked decline in humanin, but not MOTS-c, levels in breast cancer patients (P < 0.001). CONCLUSION: Our research has shown, for the first time, that increased MOTS-c and decreased humanin levels play a role in lung cancer and breast cancer, respectively. Additionally, radiotherapy modifies MOTS-c levels in patients with lung, but not breast cancer.

Zinc Sulfate and/or Growth Hormone Administration for the Prevention of Radiation-Induced Dermatitis: a Placebo-Controlled Rat Model Study.

Growth hormone (GH) and zinc (Zn) were evaluated for their potential to prevent radiation injury using a rat model of radiation-induced skin injury. Sprague-Dawley rats were divided into five groups: a control group not receiving Zn, GH, or irradiation: a radiation (RT) group receiving a single 30 Gy dose of gamma irradiation to the right hind legs; a radiation + GH group (RT + GH) receiving a single 30 Gy dose of gamma irradiation plus the subcutaneous administration of 0.01 IU kg d-1 GH; a radiation + Zn group (RT + Zn) receiving a single 30 Gy dose plus 5 mg kg d-1 Zn po; and a radiation + GH + Zn group (RT + GH + Zn) group receiving a single 30 Gy dose plus subcutaneous 0.01 IU kg d-1 GH and 5 mg kg d-1 Zn po. Acute skin reactions were assessed every 3 days by two radiation oncologists grouping. Light microscopic findings were assessed blindly by two pathologists. Groups receiving irradiation were associated with dermatitis as compared to the control group (P < 0.05). The severity of radiodermatitis in the RT + GH, RT + Zn, and RT + GH + Zn groups was significantly lower than that in the RT group (P < 0.05). Furthermore, radiodermatitis was observed earlier in the RT group than in the other treatment groups (P < 0.05). GH and Zn effectively prevented epidermal atrophy, dermal degeneration, and hair follicle atrophy. The highest level of protection against radiation dermatitis was observed in the combination group.

Evaluation of the preventive effect of dexpanthenol in radiation injury by lung perfusion scintigraphy: a preclinical experimental model of radiation injury.

AIM: The aim of this study was to show the preventative effects of dexpanthenol in radiation injuries caused by radiotherapy (RT) through the use of lung perfusion scintigraphy in the pre-RT and post-RT periods. MATERIALS AND METHODS: Six male New Zealand rabbits (5-6 months of age and ∼2.5-3 kg in weight) were the used in this study. The animals were subjected to Tc-macroaggregated albumin lung perfusion scintigraphy in the pre-RT and post-RT (i.e. 2 weeks after treatment) periods. The scintigraphies were performed with the same dose by the same staff and the methodology used the same acquisition parameters. The rabbits were divided into two groups: group I (administered RT only) and group II (also administered intramuscular 500 mg dexpanthenol injections for 14 consecutive days after RT). Quantification was performed to compare the groups and the quantification variables were compared using a paired samples t-test, with P value less than 0.05 considered to be statistically significant. Histopathological analysis was also carried out. RESULTS: The post-RT scintigraphies indicated a decrease in the counts in both lungs, suggesting early post-RT injury. The difference between the counts obtained from both lungs in groups I and II was significantly different and favoured group II. Histopathological results confirmed the scintigraphy results. CONCLUSION: It is possible to estimate post-RT changes in the early period (in contrast to previous data) by lung perfusion scintigraphy. Dexpanthenol may also reduce the effects of RT to a degree. Although this is the first study to report the preventive effects of dexpanthenol on RT injuries, further studies are warranted in this area.

Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced brain and retinal damages.

Our aim was to determine the effects of vitamin E and L-carnitine supplementation, individually or in combination, on radiation-induced brain and retinal damages in a rat model. Group 1 received no treatment (control arm). Group 2 received a total dose of 15 Gy external radiotherapy (RT) to whole brain by Cobalt-60 teletherapy machine. Groups 3, 4, and 5 received irradiation plus 40 kg(-1) day(-1) Vitamin E or 200 mg kg(-1)day(-1) L-carnitine alone or in combination. Brain and retinal damages were histopathologically evaluated by two independent pathologists. Antioxidant enzyme levels were also measured. Radiation significantly increased brain and retinal damages. A significant increase in malondialdehyde levels as well as a decrease in superoxide dismutase and catalase enzymes in brain was found in group 2. Separate administration of Vitamin E+RT and L-carnitine+RT significantly reduced the severity of brain and retinal damages and decreased the malondialdehyde levels and increased the activity of superoxide dismutase and catalase enzymes in the brain. The findings of current study support the antioxidant and radioprotective roles of vitamin E and L-carnitine. However, the combined use of Vitamin E and L-carnitine plus irradiation interestingly did not exhibit an additive radioprotective effect.

The effect of L-carnitine in the prevention of ionizing radiation-induced cataracts: a rat model.

BACKGROUND: The objective was to determine the antioxidant role of L-carnitine (LC) against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats with a single dose of 5 Gy. METHODS: Sprague-Dawley rats were used in this experiment and were divided into three groups. Group 1 did not receive LC or irradiation (control group). Group 2 received a 5 Gy gamma irradiation as a single dose to the total cranium (RT group). Group 3 received total cranium irradiation plus 100 mg/kg body weight/day LC (RT+LC group). The rats were irradiated using a cobalt-60 teletherapy unit. At the end of the 10th day, the rats were sacrificed and their eyes were enucleated. The lenticular activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. Furthermore, the lenticular content of an indicator of lipid peroxidation, malondialdehyde (MDA), was measured. RESULTS: Irradiation significantly increased the MDA level as an end product of lipid peroxidation. Irradiation also significantly decreased SOD activity and increased GSH-Px activity, indicating the generation of oxidative stress and an early protective response to oxidative damage. Irradiation with 5 Gy to the total cranium as a single fraction formed cataracts in the rat lenses. Cataract development was detectable in 9 rats in the RT group, and in only 4 rats in the RT+LC group 10 days after irradiation. LC administration plus irradiation significantly decreased the MDA level and increased the activity of SOD and GSH-Px enzymes, which might indicate the protection of the lenses from gamma radiation-induced cataracts. CONCLUSIONS: L-carnitine may protect against the damage produced by gamma radiation by increasing the activity of the SOD enzyme and by scavenging free radicals generated by ionizing radiation. As a result of this process, MDA as an indicator of lipid peroxidation may decrease.

Radioprotective effects of melatonin on radiation-induced cataract.

One of the mechanisms proposed to explain lens opacification is the oxidation of crystallins, either by radiation or reactive oxygen species (ROS). It has been shown that melatonin has both an anti-peroxidative effect on several tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant role of melatonin (5 mg/kg/day) against radiation-induced cataract in the lens after total-cranium irradiation of rats with a single dose of 5 Gy. Sprague-Dawley rats were divided into four groups. Control group received neither melatonin nor irradiation. Irradiated rats (IR) and melatonin+irradiated rats (IR+Mel) groups were exposed to total cranium irradiation of 5 Gy in a single dose by using a cobalt-60 teletherapy unit. IR+Mel and melatonin (Mel) groups were administered 5 mg/kg melatonin daily by intraperitoneal injections during ten days. Chylack's cataract classification was used in this study. At the end of the 10th day, the rats were killed and their eyes were enucleated to measure the antioxidant enzymes i.e. the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and lipid peroxidation level (malondialdehyde (MDA)). Irradiation significantly increased the MDA level, as an end product of lipid peroxidation, and also significantly decreased SOD and GSH-Px activity, emphasizing the generation of increased oxidative stress. Rats injected with melatonin only did not cause cataract formation. Melatonin supplementation with irradiation significantly increased the activity of SOD and GSH-Px enzymes and significantly decreased the MDA level. Total cranium irradiation of 5 Gy in a single dose enhanced cataract formation, and melatonin supplementation protected the lenses from radiation-induced cataract formation. Our results suggest that supplementing cancer patients with adjuvant therapy of melatonin may reduce patients suffering from toxic therapeutic regimens such as chemotherapy and/or radiotherapy and may provide an alleviation of the symptoms due to radiation-induced organ injuries.

Effects of oral Ginkgo biloba supplementation on cataract formation and oxidative stress occurring in lenses of rats exposed to total cranium radiotherapy.

PURPOSE: To determine the antioxidant role of Ginkgo biloba (GB) in preventing radiation-induced cataracts in the lens after total-cranium irradiation of rats with a single radiation dose of 5 Gy. METHODS: Sprague-Dawley rats were randomly divided into three groups. Group 1 received neither GB nor irradiation (control group). Group 2 was exposed to total-cranium irradiation of 5 Gy in a single dose [radiation therapy (RT) Group], and group 3 received total cranium irradiation from a cobalt-60 teletherapy unit, plus 40 mg/kg per day GB (RT+GB group). At the end of the tenth day, the rats were killed and their eyes were enucleated to measure the antioxidant enzymes, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the lipid peroxidation level [malondialdehyde (MDA)]. RESULTS: Irradiation significantly increased both the MDA level and the activity of GSH-Px, and significantly decreased the activity of SOD in the rat lenses. GB supplementation significantly increased the activities of SOD and GSH-Px enzymes and significantly decreased the MDA level. Total cranium irradiation of 5 Gy in a single dose promoted cataract formation, and GB supplementation protected the lenses from radiation-induced cataracts. CONCLUSIONS: We suggest that Ginkgo biloba is an antioxidant that protects the rat lens from radiation-induced cataracts.

Zinc sulfate in the prevention of total-body irradiation-induced early hematopoietic toxicity: a controlled study in a rat model.

Exposure to ionizing total-body radiation suppresses hematopoiesis, resulting in decreased production of blood cells. Many researchers have demonstrated the critical role of zinc (Zn) in diverse physiological processes, such as growth and development, maintenance and priming of the immune system, and tissue repair. The aim of the present study was to determine the effects of zinc sulfate (40 mg/kg and 80 mg/kg) on early hematopoietic toxicity, caused by total-body irradiation (TBI) of rats with a single dose of 8 Gy. Both in the Zn 40 and in the Zn 80 groups, there were significantly increased white blood cell (WBC) count, when compared with control group. The WBC count was higher in the control group than in the TBI group. This result was statistically significant (p<0.05). Both the TBI+Zn 40 and the TBI+Zn 80 groups had a significantly protected WBC count against TBI. No difference was detected in any final measurement of thrombocyte count and hemoglobin level with direct comparison among all groups, with the exception that the hemoglobin level in the Zn 80 group compared to the control group. Whereas hemoglobin level in the control group was at a median figure of 13.98 g/dL (13.30-14.80), it was at a median figure of 14.25 g/dL (14.10-15.50) in the Zn 80 group. It would be worthwhile studying the effect of oral zinc sulfate supplements in radiation-treated cancer patients, in the hope of reducing radiation-induced toxicity.

Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study.

PURPOSE: To determine the effect of oral zinc sulphate supplementation on radiation-induced oropharyngeal mucositis in patients with head-and-neck cancer. MATERIALS AND METHODS: Thirty patients with head-and-neck cancer were randomly assigned to receive either zinc sulfate or placebo. Primary tumors were localized in the larynx in 14 patients, in the nasopharynx in 4, in the oral cavity in 4, in a salivary gland in 1, in the maxillary sinus in 1, in neck nodes (lymphoma presenting primarily) in 3 and in neck metastases from an unknown primary in 3. In the placebo group, 3 patients were excluded; 1 patient died during treatment, 1 left the study, and 1 did not come to the 6 week control visit. The patients were treated with telecobalt radiotherapy at conventional fractionation (2 Gy/fraction, five fractions weekly, for 20-35 fractions within 4-7 weeks). The median radiation dose was 6400 cGy (4000-7000 cGy). Oral mucositis was assessed by two independent physicians, experts in radiation oncology, using the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring criteria. RESULTS: In the zinc sulfate group, Grade 3-4 mucositis was not detected in any patient; Grade 0 mucositis was detected in 2, and Grade 1 in 8, and Grade 2 in 5 patients. In the placebo group, Grade 2 mucositis was detected in 4 and Grade 3 in 8 patients. We observed that the degree of mucositis in the patients in the zinc sulfate group was significantly lower than that in the placebo group (p < 0.05). Confluent mucositis developed earlier in the placebo group than in the zinc sulfate group after the onset of treatment (p < 0.05) and started to improve sooner in the zinc sulfate group than in the placebo group (p < 0.05). CONCLUSIONS: Zinc sulfate is beneficial in decreasing the severity of radiation-induced mucositis and oral discomfort. These results should be confirmed by additional evaluation in randomized studies with a larger number of patients.

The effect of zinc sulphate in the prevention of radiation-induced dermatitis.

There is currently substantial clinical interest in zinc (Zn) as a protective agent against radiation-related normal tissue injury. To further assess this drug's potential, the effect of Zn was studied in rats using a radiation-induced skin injury model. Sprague-Dawley rats were divided into four groups. Group 1 received neither Zn nor irradiation (control group). Group 2 received 30 Gy of gamma irradiation as a single dose to the right hind legs of the rats (RT Group). Groups 3 and 4 received the same irradiation plus 5 mg/kg/day Zn (RT+5 Zn group) or 10 mg/kg/day Zn orally (RT+10 Zn group), respectively. The rats were irradiated using a cobalt-60 teletherapy unit. Acute skin reactions were assessed every three days by two independent radiation oncology experts. At the endpoint of the study, light-microscopic findings were assessed by two independent expert pathology physicians. Clinically and histopathologically, irradiation increased dermatitis when compared with the control group (p < 0.05). The severity of radiodermatitis of the rats in the RT+5 Zn and RT+10 Zn groups was significantly lower than in the RT group (p < 0.05); radiodermatitis was seen earlier in the RT group than in the other groups (p < 0.05). Zn was found to be efficacious in preventing epidermal atrophy, dermal degeneration such as edema and collagen fiber loss, and hair follicle atrophy. The most protection for radiation dermatitis was observed in the RT+10 Zn group. It would be worthwhile studying the effects of zinc sulphate supplements in radiation-treated cancer patients, in the hope of reducing radiation-induced toxicity.

Protective effect of melatonin against fractionated irradiation-induced epiphyseal injury in a weanling rat model.

The effects of melatonin, a free-radical scavenger and a general antioxidant, on radiation-induced growth plate injury have not been studied previously. The purpose of this study was to determine the potential benefits of sparing longitudinal bone growth by fractionated radiotherapy alone compared with pretreatment with melatonin that provides differential radioprotection of normal cells. Weanling 4-wk-old (75-100 g) male Sprague-Dawley rats were randomly assigned to one of three groups: Group R received fractionated radiation alone (n = 8); groups M5 (n = 8) and M15 (n = 7) received 5 or 15 mg/kg melatonin prior to fractionated radiation, respectively. The distal femur and proximal tibia in the right leg of each animal were exposed to a therapeutic X-irradiation dose (25 Gy total in three fractions) with the contralateral left leg as the non-irradiated control. Melatonin was administered intraperitoneally to the animals 30 min before radiation exposure. Six weeks after treatment, the rats were killed and the lower limbs disarticulated, skeletonized, radiographed, and bone growth was calculated based on measurement of the bone lengths. Fractionated radiation resulted in a mean percent overall limb growth loss of 41.2 +/- 9.5 and a mean percent overall limb discrepancy of 11.2 +/- 2.2. The administration of 5 or 15 mg/kg melatonin before each of the three fractions of radiotherapy reduced the mean percent overall limb growth loss to 33.9 +/- 5.8 and 32.2 +/- 4.5, respectively, and the mean percent overall limb discrepancy to 9.4 +/- 1.6 and 8.9 +/- 1.1, respectively; these values were significantly different compared with irradiation alone (range: P = 0.01-0.04). When compared with Group R, the growth arrest recovered by 5 or 15 mg/kg melatonin was 19.7 and 24.1% for the tibia, 7 and 18.6% for the femur, and 17.7 and 21.8% for the total limb, respectively. These results support further investigation of melatonin in combination with fractionation for potential use in growing children requiring radiotherapy to the extremity for malignant tumors.