Screening of a large panel of gastrointestinal peptide plasma levels is not adapted for the evaluation of digestive damage following irradiation

2004 ◽  
Vol 82 (2) ◽  
pp. 103-113 ◽  
Author(s):  
I Dublineau ◽  
N Dudoignon ◽  
P Monti ◽  
O Combes ◽  
J Wysocki ◽  
...  
Keyword(s):  
Substance P ◽  
Plasma Levels ◽  
Fold Increase ◽  
Biological Indicators ◽  
Whole Body ◽  
Histopathological Study ◽  
Specific Response ◽  
X Irradiation ◽  
Radiation Induced ◽  
Tract Damage

The aim of this study was to assess the potential of gastrointestinal peptide plasma levels as biomarkers of radiation-induced digestive tract damage. To this end, plasma levels of substance P, GRP, motilin, PYY, somatostatin-28, gastrin, and neurotensin were followed for up to 5 days in pigs after a 16-Gy whole-body X-irradiation, completed by a histopathological study performed at 5 days. Each peptide gave a specific response to irradiation. The plasma levels of GRP and substance P were not modified by irradiation exposure; neither were those of motilin and PYY. Concerning gastrin, a 2–3-fold increase of plasma concentration was observed in pig, which presented the most important histological alterations of the stomach. The plasma levels of somatostatin, unchanged from 1 to 4 days after irradiation, was also increased by 130% at 5 days. In contrast, a diminution of neurotensin plasma levels was noted, firstly at 1 day (–88%), and from 3 days after exposure (–50%). The present study suggested that changes in gastrin and neuro tensin plasma levels were associated with structural alterations of the stomach and ileum, respectively, indicating that they may be relevant biological indicators of radiation-induced digestive damage to these segments.Key words: gastrin, neurotensin, somatostatin, PYY, substance P, irradiation.

Mitigation of Radiation-induced Gastrointestinal System Injury using Resveratrol or Alpha-lipoic Acid: A Pilot Histopathological Study

2020 ◽  
Vol 19 (4) ◽  
pp. 413-424
Author(s):  
Bagher Farhood ◽  
Gholamreza Hassanzadeh ◽  
Peyman Amini ◽  
Dheyauldeen Shabeeb ◽  
Ahmed Eleojo Musa ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Gamma Ray ◽  
Morphological Changes ◽  
Gastrointestinal System ◽  
Alpha Tocopherol ◽  
Whole Body ◽  
Histopathological Study ◽  
Alpha Lipoic Acid ◽  
Pilot Investigation ◽  
Radiation Induced

Aim: In this study, we aimed to determine possible mitigation of radiationinduced toxicities in the duodenum, jejunum and colon using post-exposure treatment with resveratrol and alpha-lipoic acid. Background: After the bone marrow, gastrointestinal system toxicity is the second critical cause of death following whole-body exposure to radiation. Its side effects reduce the quality of life of patients who have undergone radiotherapy. Resveratrol has an antioxidant effect and stimulates DNA damage responses (DDRs). Alpha-lipoic acid neutralizes free radicals via the recycling of ascorbic acid and alpha-tocopherol. Objective: This study is a pilot investigation of the mitigation of enteritis using resveratrol and alpha-lipoic acid following histopathological study. Methods: 60 male mice were randomly assigned to six groups; control, resveratrol treatment, alpha-lipoic acid treatment, whole-body irradiation, irradiation plus resveratrol, and irradiation plus alpha-lipoic acid. The mice were irradiated with a single dose of 7 Gy from a cobalt-60 gamma-ray source. Treatment with resveratrol or alpha-lipoic acid started 24 h after irradiation and continued for 4 weeks. All mice were sacrificed after 30 days for histopathological evaluation of radiation-induced toxicities in the duodenum, jejunum and colon. Results and Conclusion: Exposure to radiation caused mild to severe damages to vessels, goblet cells and villous. It also led to significant infiltration of macrophages and leukocytes, especially in the colon. Both resveratrol and alpha-lipoic acid were able to mitigate morphological changes. However, they could not mitigate vascular injury. Conclusion: Resveratrol and alpha-lipoic acid could mitigate radiation-induced injuries in the small and large intestine. A comparison between these agents showed that resveratrol may be a more effective mitigator compared to alpha-lipoic acid.

scholarly journals Protection from Radiation-induced Damage in Rat’s Ileum and Colon by Combined Regimens of Melatonin and Metformin: A Histopathological Study

2020 ◽  
Vol 19 (2) ◽  
pp. 180-189 ◽  
Author(s):  
Masoud Najafi ◽  
Mohsen Cheki ◽  
Gholamreza Hassanzadeh ◽  
Peyman Amini ◽  
Dheyauldeen Shabeeb ◽  
...  
Keyword(s):  
Whole Body ◽  
Gastrointestinal Disorders ◽  
Histopathological Study ◽  
Radiation Toxicity ◽  
Pharmaceutical Treatment ◽  
Tissue Samples ◽  
Melatonin Administration ◽  
Male Wistar Rats ◽  
Radiation Induced ◽  
High Doses

Background: Radiation-induced enteritis and proctitis are common side effects of abdominopelvic cancers among patients that undergo radiotherapy for prostate, colorectal or urinary cancers. Exposure of these tissues to high doses of radiation leads to damage to villous, inflammation, pain, ulcer and bleeding, which may cause malabsorption and gastrointestinal disorders. To date, several procedures such as pharmaceutical treatment have been proposed for protection and mitigation of gastrointestinal toxicity following radiotherapy. Aims: In the current study, we aimed to investigate the possible radioprotection of ileum and colon in rats using a combination of melatonin and metformin. Methods: In this experimental study, 30 male Wistar rats were randomly assigned to six groups: control, melatonin (100 mg/kg) treatment, melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment, radiation (10 Gy to whole body) group, radiation + melatonin (100 mg/kg) treatment, and radiation + melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment. After 3.5 days, rats were sacrificed and their ileum and colon tissues carefully removed. Histopathological evaluations were conducted on these tissue samples. Results: Histological evaluations reported moderate to severe damages to ileum and colon following whole body irradiation. Melatonin administration was able to protect the ileum remarkably, while the combination of melatonin and metformin was less effective. Interestingly, for the colon, melatonin was less effective while its combination with metformin was able to protect against radiation toxicity completely. Conclusion: For the ileum, melatonin was a more effective radioprotector compared to its combination with metformin. However, the combination of melatonin and metformin can be proposed as an ideal radioprotector for the colon.

Effect of Two Graded Doses of Whole-Body X-Irradiation and Radioprotection by the Use of S-Phenethyl Formamidino 4 (N-Ethyl Isothioamide) Morpholine Dihydrochloride

1983 ◽  
Vol 22 (05) ◽  
pp. 237-245 ◽  
Author(s):  
P. K. Chaturvedi ◽  
S. N. Pandeya ◽  
S. S. Hasan
Keyword(s):  
Radiation Effects ◽  
Whole Body ◽  
X Irradiation ◽  
Radiation Induced ◽  
Induced Changes ◽  
The Brain

The protection offered by a newly synthesized compound (S-phenethyl-formamidino-4(N-ethyl isothioamide) morpholine dihydrochloride) against radiation effects on DNA, RNA and protein biosynthetic processes in the brain, and on metabolites of 5-HT and nor-adrenalin, i.e., 5-HIAA and VMA, in the urine, including the radiobiological damage to thyroid and testes, was evaluated. The use of the compound prior to irradiation prevented radiation-induced changes in the thyroid and testes. The radiation-induced alterations in the pattern of DNA, RNA, protein in the brain, and in 5-HIAA and VMA in urine could be averted by treatment with this compound prior to each dose of X-irradiation.

THE SENSITIVITY OF VARIOUS GERM-CELL STAGES OF THE MALE MOUSE TO RADIATION INDUCED TRANSLOCATIONS

1968 ◽  
Vol 10 (3) ◽  
pp. 495-507 ◽  
Author(s):  
A. Léonard ◽  
Gh. Deknudt
Keyword(s):  
Chromosomal Abnormalities ◽  
Virgin Female ◽  
Whole Body ◽  
Reciprocal Translocations ◽  
Control Series ◽  
The Third ◽  
Metaphase Stage ◽  
X Irradiation ◽  
Radiation Induced ◽  
Mature Spermatozoa

Adult male BALB/c mice were given whole body X-irradiation with 300 R. Directly after X-irradiation each male was mated to one virgin female of the same strain and received one fresh female per week during 9 weeks. The male F1 offspring was killed when mature and the testes removed and analysed for the presence of chromosome rearrangements at diakinesis — first metaphase stage of meiosis. Whereas no aberration was recorded among the 171 F1 ♀♀ from the control series, chromosomal abnormalities were observed in 41 F1 ♀♀ from the irradiated series. The incidence of males with aberrations was respectively 5.1% the first week, 10.4% the second week, 21.7% the third week, 2.2% the fourth week and 6.3% the fifth. No aberration was observed in the 129 F1 males sired between the sixth and ninth weeks. It may be concluded that irradiated spermatids yield approximately four times as many cases of aberration in viable F1 ♀♀ as do irradiated mature spermatozoa and about ten times as many as the most mature spermatocytes whereas no aberrations were recovered from irradiation of the spermatogonia. The most common aberrations found in the F1 males of the irradiated series were the reciprocal translocations.

Effect of repeated whole-body x-irradiation on peripheral white blood cell count of rabbits

1959 ◽  
Vol 197 (3) ◽  
pp. 568-570
Author(s):  
Herbert B. Gerstner ◽  
Harry A. Gorman
Keyword(s):  
Blood Cell ◽  
Cell Count ◽  
White Blood Cell Count ◽  
White Blood Cell ◽  
White Blood Cells ◽  
Whole Body ◽  
Blood Cell Count ◽  
Significant Difference ◽  
X Irradiation ◽  
Radiation Induced

Six groups of rabbits received whole-body x-irradiation of 0, 100, 200, 300, 400 and 500 r, respectively. Counts of total white blood cells were performed regularly until 11 weeks post exposure when radiation-induced leucopenia had disappeared in all groups. At that time, the animals were re-exposed to the same doses and white cells were once more counted throughout 11 weeks. Then followed a third application of the same doses with subsequent observation of white counts. Statistical analysis of data yielded the following results: in the three exposures, radiation-induced leucopenia showed no significant difference with respect to rate of development, maximal degree and rate of disappearance. Therefore, as judged by the white blood cell count, susceptibility to ionizing radiation appeared unaltered by previous exposure to appreciable doses when the interval between exposures was sufficiently long to permit complete hematopoietic recovery.

scholarly journals IKKβ Inhibitor IMD-0354 Attenuates Radiation Damage in Whole-body X-Irradiated Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Kengo Waga ◽  
Masaru Yamaguchi ◽  
Shuta Miura ◽  
Teruki Nishida ◽  
Akiko Itai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Survival Rate ◽  
Critical Role ◽  
Reactive Oxygen Species Generation ◽  
Whole Body ◽  
Spleen Cells ◽  
Antitumor Effects ◽  
X Irradiation ◽  
Radiation Induced ◽  
Complex Signaling

Nuclear factor-kappa B (NF-κB) transcription factor plays a critical role in regulating radiation-induced inflammatory and immune responses. Intracellular reactive oxygen species generation induces the activation of NF-κB via the inhibitor of κB (IκB) kinase (IKK) complex signaling. Previous studies have reported that the inhibition of IKK-driven NF-κB activation offers a therapeutic strategy for managing inflammatory disorders and various cancers, but it has additionally been reported that treatment targeting NF-κB also shows a radioprotective effect. IMD-0354 is an IKKβ inhibitor that blocks IκBα phosphorylation in the NF-κB pathway. This compound is known to exert anti-inflammatory and antitumor effects, but its radioprotective effects are unclear. Therefore, in the present study, we examined whether or not IMD-0354 has a mitigative effect on radiation-induced damages in mice. IMD-0354 was dissolved in soybean oil and subcutaneously administered to C57BL/6J Jcl mice for 3 consecutive days after 7 Gy of whole-body X-irradiation. The survival rate on day 30 and the NF-κB p65 and IκBα in bone marrow and spleen cells based on flow cytometry were assessed. IMD-0354 administration significantly suppressed the lethality induced by whole-body X-irradiation, and the survival rate increased by 83%. The NF-κB p65 and IκBα in bone marrow and spleen cells were significantly lower in IMD-0354-treated mice than in irradiated mice, suggesting that the IKKβ inhibitor IMD-0354 exerts a radiomitigative effect by suppressing the NF-κB.

Mitigation of Radiation-Induced Gastrointestinal System Injury by Melatonin: A Histopathological Study

2020 ◽  
Vol 12 (1) ◽  
pp. 72-79
Author(s):  
Hossein Sadeghi ◽  
Hamed Bagheri ◽  
Babak Shekarchi ◽  
Abdolreza Javadi ◽  
Masoud Najafi
Keyword(s):  
Gamma Ray ◽  
Radiation Treatment ◽  
Cell Damage ◽  
Gastrointestinal System ◽  
Whole Body ◽  
Histopathological Study ◽  
Radiation Toxicity ◽  
Melatonin Treatment ◽  
Gastrointestinal Injury ◽  
Radiation Induced

Aims : The current study aimed to investigate the potential role of melatonin in the mitigation of radiation-induced gastrointestinal injury. Background: Organs of the gastrointestinal system such as the intestines, colon, duodenum, ileum etc. are sensitive to ionizing radiation. Mitigation of radiation-induced gastrointestinal injury is an interesting topic in radiobiology and a life-saving approach for exposed persons after a radiation event or improving the quality of life of radiotherapy patients. Methods: 40 male mice were randomly assigned into four groups namely G1: control, G2: melatonin treatment, G3: whole-body irradiation, and G4: melatonin treatment after whole-body irradiation. A cobalt-60 gamma-ray source was used to deliver 7 Gy to the whole body. 100 mg/kg melatonin was administered orally 24 h after irradiation and continued for 5 days. Thirty days after irradiation, histopathological evaluations were performed. Results: The whole-body irradiation led to remarkable inflammation, villi shortening, apoptosis and damage to goblet cells of the small intestine. Furthermore, moderate to severe inflammation, apoptosis, congestion, crypt injury and goblet cell damage were reported for the colon. Treatment with melatonin after whole-body irradiation led to significant mitigation of radiation toxicity in both small and large intestines. Conclusion: Melatonin could mitigate intestinal injury following whole-body exposure to radiation. Treatment with melatonin after an accidental exposure to radiation may increase survival via mitigation of damages to radiosensitive organs, including the gastrointestinal system.

Urinary Excretion and Plasma Levels of Free Ninhydrin Reactive Compounds in X-Irradiated Rats

1956 ◽  
Vol 186 (1) ◽  
pp. 175-179 ◽  
Author(s):  
R. E. Kay ◽  
D. C. Harris ◽  
C. Entenman
Keyword(s):  
Amino Acids ◽  
Urinary Excretion ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Liver Glycogen ◽  
Cysteic Acid ◽  
Whole Body ◽  
X Rays ◽  
X Irradiation ◽  
Sulfur Containing

Urinary excretion and plasma levels of ninhydrin-reactive compounds in x-irradiated rats were quantitatively studied. In the urinary excretion studies fasted rats were exposed to either a sublethal (450 r) or superlethal (2500 r) dose of whole-body 250 kvp x-rays. Twenty-four-hour urines, taken from two days preirradiation to 3 days postirradiation, were analyzed for ninhydrin-reactive compounds. During the day following x-irradiation, rats exposed to either sublethal or superlethal irradiation excreted increased amounts of urinary taurine, cysteic acid, leucine and valine. In the plasma studies four groups of rats were exposed to 600 r of whole-body x-irradiation. At 6, 12, 24 and 30 hours after irradiation plasma was analyzed for ninhydrin-reactive compounds and creatinine. Transitory elevations in plasma concentrations of lysine, glutamine, taurine, methionine, valine and leucine were observed, while elevations in the levels of arginine, serine plus glycine, threonine, alanine and creatinine were not noted. The increased urinary excretion of nonglycogenic amino acids and the increased plasma concentrations of the nonglycogenic amino acids may be the result of a breakdown of protein or protein-like compounds to amino acids with the subsequent rapid conversion of the excess glycogenic amino acids to liver glycogen. The early excessive excretion of taurine in the x-irradiated rat suggests an increased oxidation of sulfur containing compounds.

scholarly journals IN VIVO RADIOPROTECTIVE EFFECTS OF WHEATGRASS (TRITICUM AESTIVUM) EXTRACT AGAINST X-IRRADAITION-INDUCED OXIDATIVE STRESS AND APOPTOSIS IN PERIPHERAL BLOOD LYMPHOCYTES IN RATS

2018 ◽  
Vol 11 (4) ◽  
pp. 239
Author(s):  
Chandresh Shyam ◽  
Devinder K Dhawan ◽  
Vijayta D Chadha
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Treated Group ◽  
Whole Body ◽  
Control Group ◽  
X Rays ◽  
X Ray ◽  
Peripheral Lymphocytes ◽  
X Irradiation ◽  
Radiation Induced

 Objectives: The present study was undertaken to investigate the possible protective potential of wheatgrass extract against radiation-induced toxicity in peripheral lymphocytes of rats exposed to a fractionated dose of X-rays.Methods: Effects of the X-irradiation with and without wheatgrass were studied on various parameters in peripheral lymphocytes including antioxidant defense system and apoptosis. Male Sprague-Dawley rats were divided into four different groups: Normal control group, X-ray-irradiated group (21 Gy over a span of 7 days), wheatgrass-treated group (80 mg/100 g bodyweight for 2 weeks), and X-rays-irradiated + wheatgrass-treated group. All the biochemical indices which included lipid peroxidation (LPO), reduced glutathione, reactive oxygen species (ROS), and activities of antioxidant enzymes were investigated in lymphocytes. Terminal deoxynucleotidyl transferase dUTP nick-end labeling assay was carried out to assess the apoptosis in lymphocytes following whole-body X-irradiation.Results: Whole-body X-irradiation to rats resulted in significant increase in LPO with concomitant depression of antioxidant enzymes activities, namely, superoxide dismutase, catalase, and glutathione peroxidise (GPx) in lymphocytes. Further, the present study witnessed a significant increase in the number of apoptotic lymphocytes in the X-irradiated animals. However, wheatgrass supplementation lowered the LPO levels, restored cellular antioxidant status, and provided significant protection against radiation-induced apoptosis.Conclusions: Based on these observations, the present study suggests that wheatgrass extract has the potential to be used as an effective radioprotectant against radiation-induced oxidative stress and apoptosis in peripheral lymphocytes of whole-body X-ray-exposed rats.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

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