Total Cranial Irradiation Research Articles

Nigella sativa oil reduces oxidative/nitrosative stress in the salivary gland of rats exposed to total cranial irradiation

Patients with head and neck cancer who receive radiotherapy experience serious side-effects during and after their treatment. Radiotherapy affects the salivary glands, causing a change in the composition of the saliva and a decrease in its flow. In this study, we aimed to investigate whether Nigella sativa oil (NSO) has a possible protective effect in preventing the harmful effects of free radicals formed by radiotherapy in rats. Thirty-six male Wistar-Albino rats weighing 200 ± 20 g were used. The rats were randomly divided into four groups: control, sham, irradiation (IR), and IR plus NSO groups. Xanthine oxidase (XO), nitric oxide synthase (NOS) activities, nitric oxide (NO•), peroxynitrite (ONOO−), malondialdehyde (MDA) levels were determined in salivary tissue of rats. NOS, XO activities, NO•, ONOO−, and MDA values were found to be significantly higher in the irradiated rats only compared to all other groups. As a results, NSO reduces oxidative/nitrosative stress markers and has antioxidant effects, which also augments the antioxidant capacity in the salivary tissue of rats.

Radioprotective effect of thymoquinone on salivary gland of rats exposed to total cranial irradiation

The purpose of this study was to investigate the radioprotective effects of thymoquinone against radiation-induced damage in the salivary glands of rats exposed to total cranial gamma irradiation. Thirty-two Sprague-Dawley rats were divided into 4 groups to test the radioprotective effectiveness of thymoquinone by intraperitoneal injection. An appropriate control group was also studied. Biochemical parameters in liver tissue of rats were determined by spectrophotometer. Glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), total (enzymatic plus nonenzymatic) superoxide scavenger activity (TSSA), nonenzymatic superoxide scavenger activity (NSSA), and superoxide dismutase (SOD) activities were significantly decreased, whereas xanthine oxidase, nitric oxide synthase activities, malondialdehyde, nitric oxide, and peroxynitrite levels were significantly increased in the irradiation group when compared to the control and sham control groups. Results showed that thymoquinone reduces oxidative and nitrosative stress parameters and has antioxidant effects and a free radical scavenging activity.

245 - The Radioprotective Effects of Propolis and Caffeic Acid Phenethyl Ester on Radiation-Induced Oxidative/nitrosative Stress in Brain Tissue

Head and neck cancer patients treated with radiotherapy suffer severe side effects during and following their treatment. Efforts to decrease toxicity of irradiation to normal tissue, organs and cells have led to searching for cytoprotective agent. Investigations for effective and non-toxic compounds with radioprotective capability led to increasing interest in antioxidant such as Propolis and Caffeic acid phenethyl ester (CAPE). The aim of this study was to evaluate the antioxidant and radioprotective effects of Propolis and CAPE on radiation-induced oxidative/nitrosative stress in the brain tissue. Fourty Sprague-Dawley rats were randomly divided into five groups. Group 1 (Irradiation (IR) + Propolis) received total cranium irradiation and propolis was given orally through an orogastric tube daily. Group 2 (IR+CAPE) received total cranium irradiation plus CAPE, was dissolved in dimethyl sulfoxide (DMSO) just before giving to the rats, intraperitoneally (IP) every day. Group 3 (IR) received 5 Gy of gamma irradiation as a single dose to total cranium plus 1 ml saline daily. Group 4 received daily plain DMSO. Group 5 received daily plain saline. At the end of the 10 day time period, xanthine oxidase (XO), nitric oxide synthase (NOS) activities, nitric oxide (NO●) and peroxynitrite (ONOO–) levels were significantly higher in IR group compared to all other groups. In conclusion, the results suggest the radioprotective ability of Propolis and CAPE involving prevention of radiation-induced oxidative/nitrosative damage.

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English

Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling

Background/Aims: Recent studies have shown that thymoquinone (TQ) exerts protective effects against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats. Nevertheless, there is no published work investigated the effects of TQ on T cell development and biology in animal models exposed to gamma radiation. Therefore, in the present study we focused on determining the effects of TQ on radiation damage in the thymus, radiation-induced T cell imbalance, and on immune dysfunction induced by gamma-rays. Methods: Three groups of rats were used: a control group, a gamma-irradiated group, and a gamma-irradiated group that was orally supplemented with TQ. Serum lipid profiles, malondialdehyde (MDA) levels, and pro-inflammatory cytokine levels were measured to assess gamma irradiation-induced oxidative stress and inflammatory capacity. T cell apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometry analysis. The expression of pro-apoptotic proteins such as Bax and caspase-3, the anti-apoptotic protein Bcl-2, and an exhaustion marker of T cells (PD-1) in CD4⁺ and CD8⁺ T cell populations was evaluated using flow cytometry analysis. The T cell architecture of the thymus gland was evaluated by histological analysis. Results: Exposure to gamma radiation increased triglyceride, cholesterol, LDL-C, MDA, TNF-α and IL-6 levels and decreased HDL-C levels. The altered lipid profile and MDA and pro-inflammatory cytokine (TNF-α and IL-6) levels induced by exposure to gamma radiation were significantly restored in TQ-treated gamma-irradiated rats. Rats exposed to gamma radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and upregulation of PD-1, Bax, and caspase-3 expression, which sensitized these cells to apoptosis. Interestingly, treatment of gamma-irradiated rats with TQ decreased T cell exhaustion and apoptosis by modulating the expression of Bcl-2, PD-1, Bax, and caspase-3. Conclusions: Our results provide evidence for the beneficial effects of TQ as an effective radioprotective candidate that enhances cellular immunity.

211 - Nigella Sativa Oil Attenuates Oxidative Stress in Salivary Gland of Rats Exposed to Total Cranial Irradiation

211 - Nigella Sativa Oil Attenuates Oxidative Stress in Salivary Gland of Rats Exposed to Total Cranial Irradiation

The radioprotective effect of Nigella sativa on nitrosative stress in lens tissue in radiation-induced cataract in rat

Objective: The aim of this study was to investigate the antioxidant and radioprotective effects of Nigella sativa oil (NSO) and thymoquinone (TQ) against ionizing radiation-induced cataracts in lens after total cranium irradiation (IR) of rats with a single dose of 5 gray (Gy).Materials and methods: Seventy-four Sprague-Dawley rats were used for the experiment. The rats were randomly divided into six groups. Group A received total cranium IR plus NSO (1 g kg–1 d–1) orally through an orogastric tube. Group B received total cranium IR plus TQ (50 mgkg–1 d–1) daily by intraperitoneal injection. Group C received 5 Gy of gamma IR as a single dose to total cranium plus 1 ml saline. Group D1 just received 1 ml saline. Group D2 just received dimethyl sulfoxide. Group D3 did not receive anything.Results: At the end of the 10th d, cataract developed in 80% of the rats in IR group only. After IR, cataract rate dropped to 20% and 50% in groups which were treated with NSO and TQ, respectively, and was limited at grades 1 and 2. Nitric oxide synthase activity, nitric oxide and peroxynitrite levels in the radiotherapy group were higher than those of all other groups.Conclusions: The results implicate a major role for NSO and TQ in preventing cataractogenesis in ionizing radiation-induced cataracts in the lenses of rats, wherein NSO were found to be more potent.

Whole-brain irradiation increases NREM sleep and hypothalamic expression of IL-1β in rats

Purpose: Although it has mainly been described qualitatively, whole brain irradiation induces somnolence in patients with malignant diseases. Therefore, we used a rat model to quantify the effects of irradiation of healthy brain tissue on both sleep-wake patterns and the expression of the pro-inflammatory cytokine interleukin-1β (IL-1β), which is known to induce sleep.Materials and methods: Different groups were examined at three time points after irradiation (1 day, 30 days and 60 days). Polysomnographic recordings were performed on each rat before and after total cranial irradiation (12 Gy). IL-1β protein levels in several brain regions were assessed by enzyme-linked immunosorbent assays, and site-specific immunoreactivity was observed by immunofluorescence.Results: We found that both non-rapid eye movement sleep and IL-1β protein expression in the hypothalamus increased 30 days after irradiation.Conclusions: Whole brain irradiation increases sleep in our rat model, and this finding is similar to qualitative reports from patients. Because IL-1β has been proposed as a sleep-promoting molecule, we propose that the polysomnographic results may be attributable, at least in part, to the delayed overexpression of IL-1β in the hypothalamus.

Atypical herpes simplex encephalitis after total cranial irradiation

Infectious Diseases, Vanderbilt University, Nashville, TN Dr. Bloch received funding from the Centers for Disease Control and Prevention.

Zinc administration modulates radiation-induced oxidative injury in lens of rat

Background:The aim of this study was to evaluate the antioxidant role of zinc (Zn) against radiation-induced cataract in the rat lens after total cranial irradiation with a single 5 Gray (Gy) dose of gamma irradiation.Materials and Methods:Twenty-one Sprague-Dawley rats were used for the experiment. The control group did not receive Zn or irradiation but received 1-ml saline orally plus sham-irradiation. The irradiation (IR) group received 5 Gy gamma irradiation to the total cranium as a single dose plus 0.1 ml physiological saline intraperitoneally. The IR plus Zn group received irradiation to total cranium plus 10 mg/kg/day Zn intraperitoneally. Biochemical parameters measured in rat lenses were carried out using spectrophotometric techniques.Results:Lens total (enzymatic plus non-enzymatic) superoxide scavenger activity (TSSA), glutathione reductase (GRD), and glutathione-S-transferase (GST) activities significantly increased in the IR plus Zn groups when compared with the IR group. However, TSSA, GRD and GST activities were significantly lower in the IR group when compared with the control group. Lens non-enzymatic superoxide scavenger activity (NSSA) in the IR plus Zn group was significantly increased compared to that of the IR group. Lens xanthine oxidase (XO) activity in the IR group significantly increased compared to that of both the control and IR plus Zn groups.Conclusion:Zn has clear antioxidant properties and prevented oxidative stress by scavenging free radicals generated by ionizing radiation in rat lenses.

RADIOPROTECTIVE EFFECT OF MELATONIN IN REDUCING OXIDATIVE STRESS IN RAT LENSES

Objective: Ocular morbidity is widely observed when radiotherapy includes the orbit. Oxidative stress generated by irradiation is responsible for this complication. In different studies, it has been shown that melatonin has antioxidative properties and a radioprotective role. The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury in rats' lenses after total cranial irradiation. Materials and Methods: Thirty-six adult female Sprague-Dawley rats were divided into six groups. Group I was the control group, group II only received total cranial gamma irradiation of 5 Gy, group III was exposed as the second group but at the dose of 8 Gy, group IV received 30 mg/kg melatonin 30 minutes prior to radiation plus total cranial irradiation of 5 Gy plus 5 mg/kg melatonin daily through intraperitoneal injection for ten days after irradiation, group V was treated similar to the fourth group, i.e. received irradiation plus melatonin, but at the dose of 8 Gy, and group VI only received melatonin (30 mg/kg on the first day and 5 mg/kg on the following days). Ten days after irradiation, all rats were sacrificed and their eyes were enucleated to measure the biochemical parameters i.e. malondialdehyde (MDA) and glutathione (GSH). Results: The levels of MDA in rat lenses increased and the levels of glutathione in lenses decreased after gamma ray irradiation but these parameters were still within normal limits in rats that received melatonin. Conclusion: It could be concluded that melatonin is useful in preventing radiation-induced oxidative injury due to its antioxidative and free radical scavenging properties.

The effects of oral Ginkgo biloba supplementation on radiation-induced oxidative injury in the lens of rat

Background:The aim of this study was to evaluate the antioxidant role of Ginkgo biloba (GB) against radiation-induced cataract in the rat lens after total cranial irradiation with a single 5 Gray (Gy) dose of gamma irradiation.Materials and Methods:Twenty-four Sprague-Dawley rats were used for the experiment. The rats were randomly divided into three equal groups. Group 1 did not receive GB or irradiation (control group) but received 1-ml saline orally plus sham-irradiation. Group 2 received total cranium 5 Gy of gamma irradiation as a single dose (IR group) plus 1-ml saline orally. Group 3 received total cranium irradiation plus 40 mg/kg/day GBE (IR plus GBE group). Biochemical parameters measured in murine lenses were carried out using spectrophotometric techniques.Results:Lens total (enzymatic plus non-enzymatic) superoxide scavenger activity (TSSA), non-enzymatic superoxide scavenger activity (NSSA), glutathione reductase (GRD), and glutathione-S- transferase (GST) activities significantly increased in the IR plus GBE groups when compared with the IR group. However, TSSA, GRD and GST activities were significantly lower in the IR group when compared with the control group. Lens xanthine oxidase (XO) activity in the IR group significantly increased compared to that of both the control and IR plus GBE groups.Conclusion:GBE has clear antioxidant properties and is likely to be a valuable drug for protection against gamma-irradiation and/or be used as an antioxidant against oxidative stress.

Melatonin reduces oxidative stress in the rat lens due to radiation-induced oxidative injury

Purpose: The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced cataract in the rat lens after total cranial irradiation with a single 5 Gray (Gy) dose of gamma irradiation.Materials and methods: Twenty-eight Sprague-Dawley rats were used for the experiment.The rats were randomly divided into four equal groups. The control group did not receive melatonin or irradiation but received both 0.1 ml physiological saline intraperitoneally and sham irradiation. The irradiation (IR) group received 5 Gy gamma irradiation to the total cranium as a single dose plus 0.1 ml physiological saline intraperitoneally. The melatonin plus IR group received irradiation to the total cranium plus 5 mg/kg/day melatonin intraperitoneally. The melatonin group received only 5 mg/kg/day melatonin plus sham-irradiation. Biochemical parameters measured in murine lenses were carried out using spectrophotometric techniques.Results: Lens antioxidant capacity, as measured by levels of total superoxide scavenger activity (TSSA), non-enzymatic superoxide scavenger activity (NSSA) and glutathione reductase (GRD) activity, significantly increased in melatonin, control and melatonin plus IR groups when compared with the IR group. Lens glutathione-S-transferase (GST) activity significantly increased in control and melatonin groups when compared with the IR group. Lens malondialdehyde (MDA) levels significantly increased in the IR group when compared with control, melatonin and melatonin plus IR groups. Lens TSSA and NSSA activities significantly decreased in control and melatonin plus IR groups when compared with the melatonin group. Lens GST activity significantly increased in the control group when compared with melatonin plus IR group. Lens GRD activity significantly increased in melatonin and melatonin plus IR groups when compared with control group.Conclusions: Melatonin reduces oxidative stress markers and augments anti-oxidant capacity in the rat lens.

Dosimetric analysis of thyroid doses from total cranial irradiation

The purpose was to estimate the radiation dose to the thyroid from total cranial irradiation with parallel opposed lateral fields of 1.25 MeV gamma rays of (60)Co, to represent the current treatment modality, and with 6 MV photon beams derived from a linear accelerator. The mean thyroid doses were measured using thermoluminescence dosemeters in the Rando phantom with two cranial irradiation set-ups: (1) the lateral beams were angled by rotating the collimator to avoid irradiation of the lens and healthy tissues and (2) the lateral beams were not angled, and shielding blocks were used to protect the lens and healthy tissues. For a cranial dose of 18 Gy, thyroid doses for child patients for (60)Co with the open and blocked fields were 0.27 and 0.32 Gy, respectively. With 6 MV, the thyroid dose was less than the doses for (60)Co open and blocked cranial fields by 17 and 10%, respectively. Unblocked cranial fields and a high-energy photon beam should be preferred for cranial irradiation of children.

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

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. 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. 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. 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.

Effects of Piracetam Supplementation on Cochlear Damage Occuring in Guinea Pigs Exposed to Irradiation

In this study we aimed to determine the role of piracetam (PIR) in preventing radiation induced cochlear damage after total-cranium irradiation (radiotherapy; RT). Male albino guinea pigs used in the study were randomly divided into three groups. Group 1 (Control group) (n=11) received neither PIR nor irradiation, but received saline solution intraperitoneally (i.p.) and received sham irradiation. Group 2 (RT group) (n=32) was exposed to total cranium irradiation of 33 Gy in 5 fractions of 6.6 Gy/d for five successive days, with a calculated (alpha/beta=3.5) biological effective dose of fractionated irradiation equal to 60 Gy conventional fractionation, then received saline solution for five successive days i.p. Group 3 (PIR+RT group) (n=33) received total cranium irradiation, plus 350 mg/kg per day PIR for five successive days i.p. After the last dose of RT, the guinea pigs were all sacrificed at the 4th, 24th and 96th hours, respectively. Their cochleas were enucleated for histopathologic examination. It was observed that total cranium irradiation (RT group) promoted degeneration in stria vascularis (SV), spiral ganglion cells (SG), outer hair cells (OHC) and inner hair cell (IHC) of cochleas at these times (p<0.05). While in the PIR+RT group, there was no statistically significant difference on radiation-induced cochlear degeneration in SV and OHC at 4th (p>0.05) and IHC at 4th, 24th hours (p>0.05), there was a significant difference on radiation-induced cochlear degeneration in SV and OHC at 24th and 96th hours (p<0.05), IHC at 96th hour (p<0.05) and SG at 4th, 24th and 96th hours (p<0.05). There was no any cochlear degeneration in the control group. Piracetam might reduce radiation-induced cochlear damage in the guinea pig. These results are pioneer to studies that will be performed with PIR for radiation toxicity protection.

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.

Protective Role of Intramuscularly Administered Vitamin E on the Levels of Lipid Peroxidation and the Activities of Antioxidant Enzymes in the Lens of Rats Made Cataractous with Gamma-Irradiation

To determine the antioxidant role of vitamin E (VE) (10 mg/kg/day) against radiation-induced cataract in lens after total-cranium irradiation of rats with a single dose of 5 Gy. Sprague-Dawley rats were divided into three groups. Group 1 did not receive VE or irradiation but received both 0.1 ml physiologic saline intraperitoneally and sham irradiation (control group). Group 2 received to total cranium 5 Gy of gamma irradiation as a single dose (RT group) plus 0.1 ml physiologic saline intraperitoneally. Group 3 received irradiation to total cranium plus 10 mg/kg/day VE (RT+VE group). The rats were irradiated using a cobalt-60 teletherapy unit. Chylack's cataract classification (1) was used in this study. At the end of 10 days, the rats were killed and their eyes were enucleated to measure the antioxidant enzymes (the activity of superoxide dismutase [SOD], glutathione peroxidase [GSH-Px]) and lipid peroxidation level (malondialdehyde [MDA]). While grade 1 cataract development was detectable in seven rats in the RT group, it was detectable only in two rats in the RT+VE group, whereas none of the rats in the control group exhibited any biomicroscopic change in their lenses. MDA level and GSH-Px activity in the rat lens in the RT group was significantly higher than in the control group. SOD activity in the RT group was lower than in the control group. The activity of SOD and GSH-Px enzymes was higher in the RT+VE group, but MDA level was lower in the RT+VE group when compared with the RT group. Vitamin E has a protective effect on radiation-induced cataract by decreasing oxidative stress.

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

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. 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)]. 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. We suggest that Ginkgo biloba is an antioxidant that protects the rat lens from radiation-induced cataracts.