Radiation-induced Hepatic Injury Research Articles

Regulation of radiation-induced liver damage by modulation of SIRT-1 activity: In vivo rat model.

Silent information regulator 1 (SIRT-1), a nicotinamide adenine dinucleotide-dependent deacetylase, was found to regulate cell apoptosis, inflammation, and oxidative stress response in living organisms. Therefore, the role of SIRT-1 in regulating forkhead box O/poly ADP-ribose polymerase-1 (FOXO-1/PARP-1) signaling could provide the necessary validation for developing new pharmacological targets for the promotion or inhibition of SIRT-1 activity toward radiation sensitivity. In the present study, the SIRT-1 signaling pathway is being investigated to study the possible modulatory effect of resveratrol (RSV, SIRT-1 activator) versus nicotinamide (NAM, SIRT-1 inhibitor) in case of liver damage induced by whole-body gamma irradiation. Rats were exposed to 6 Gy gamma radiation after being pretreated with either RSV (10 mg/kg/day) or NAM (100 mg/kg/day) for 5 days, and subsequent examining hepatic morphological changes and apoptotic markers were assessed. The expression of SIRT-1, FOXO-1, and cleaved PARP-1 in the liver was analyzed. RSV improved radiation-induced apoptosis, mitochondrial dysfunction, and inflammation signified by low expression of caspase-3, lactate dehydrogenase, complex-I activity, myeloperoxidase, and total nitric oxide content. RSV increased the expression of SIRT-1, whereas cleaved PARP-1 and FOXO-1 were suppressed. These protective effects were suppressed by inhibition of SIRT-1 activity using NAM. These findings suggest that RSV can attenuate radiation-induced hepatic injury by reducing apoptosis and inflammation via SIRT-1 activity modulation.

An improved pseudotargeted GC–MS/MS-based metabolomics method and its application in radiation-induced hepatic injury in a rat model

The liver is the pivotal metabolic organ primarily responsible for metabolic activities, detoxification and regulation of carbohydrate, protein, amino acid, and lipid metabolism. However, very little is known about the complicated pathophysiologic mechanisms of liver injury result from ionizing radiation exposure. Therefore, a pseudotargeted metabolomics approach based on gas chromatography–tandem mass spectrometry with selected reaction monitoring (GC–MS-SRM) was developed to study metabolic alterations of liver tissues in radiation-induced hepatic injury. The pseudotargeted GC–MS-SRM method was validated with satisfactory analytical characteristics in terms of precision, linearity, sensitivity and recovery. Compared to the SIM-based approach, the SRM scanning method had mildly better precision, higher sensitivity, and wider linear ranges. A total of 37 differential metabolites associated with radiation-induced hepatic injury were identified using the GC–MS-SRM metabolomics method. Global metabolic clustering analysis showed that amino acids, carbohydrates, unsaturated fatty acids, organic acids, metabolites associated with pyrimidine metabolism, ubiquinone biosynthesis and oxidative phosphorylation appeared significantly declined after high dose irradiation exposure, whereas metabolites related to lysine catabolism, glycerolipid metabolism and glutathione metabolism presented the opposite behavior. These changes indicate energy deficiency, antioxidant defense damage, accumulation of ammonia and lipid oxidation of liver tissues in response to radiation exposure. It is shown that the developed pseudotargeted method based on GC–MS-SRM is a useful tool for metabolomics study.

Histopathological assessment of protective effects of selenium nanoparticles on rat hepatocytes exposed to Gamma radiation.

Gamma radiation are used in many medical and technical applications, however, it is one of the most dangerous kinds of radiation and can be harmful to the body. The present study was designed to clarify the protective effects of the selenium supplementation as selenium nanoparticle and selenite selenium in rat liver against Gamma irradiation with different intensities of 2.00 and 8.00 Gy. A total number of 45 healthy male Wistar rats were randomly divided into nine groups of five each. The radiation procedure was carried out in the Cobalt 60 equipment in Omid hospital, Urmia. The animals were simultaneously immobilized in a transparent acrylic plate and exposed to different intensities of 2.00 and 8.00 Gy radiations on day 7th and 14th of the experiment. After 72 hr after the last radiation, the animals were euthanized, and blood and liver tissue were collected. Histological analyses revealed the radiation-induced hepatic injury in rats, which included vacuolated cytoplasm, liver necrosis, fibrosis, and vascular lesions followed by a significant increase in alanine transaminase, alanine transaminase, alkaline phosphatase, and Gamma-glutamyl transferase. Selenium nanoparticles bear a more potent antioxidant effect in comparison with selenium selenite and can effectively protect the liver cell against Gamma radiation at a dose of 8.00 Gy.

Diagnostic value of [ $$^{18}{\text{F}}$$ 18 F ]FDG-PET/CT in acute hepatic radiation toxicity: a Tibet minipig model

There are few reports with respect to the details of acute effects (during and following RT) of ionizing radiation in liver tissue in epidemiology, pathology, physiology and imageology. Therefore, this study was undertaken to assess the diagnostic value of 2-[\({}^{18}\hbox {F}\)]-fluoro-2-deoxy-D-glucose positron emission tomography with computed tomography ([\({}^{18}\hbox {F}\)]-FDG-PET/CT) in the detection of acute radiation toxicity in normal liver using Tibet minipigs as a model. Thirty-six male Tibetan minipigs were randomly divided into six groups (\(n = 6\)). The irradiation groups were treated with a single dose of \(2, 5, 8, 11 \hbox { and } 14 \hbox { Gy}\) total body irradiation using an 8-MV X-ray linac, at dose rate of \(255 \hbox { cGy/min}\). The control group was not irradiated. The pigs were evaluated with [\({}^{18}\hbox {F}\)]-FDG-PET/CT, and their alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities and the ALT/AST ratio, INRatio and bilirubin were measured on Day 7 post-TBI. All pigs were killed on Day 7 post-TBI to collect liver tissues for pathological examination. The results showed that liver standardized uptake value (SUV) increased with the dose from 2 to 11 Gy and decreased suddenly at \(14 \hbox { Gy}\). HAI score showed a radiation dose-dependent increase of 2–11 Gy and was positively correlated with SUV (\(p<0.05\)). However, HAI score showed no correlation with liver function. Therefore, we concluded that [\({}^{18}\hbox {F}\)]-FDG-PET/CT has the potential to assess acute radiation-induced hepatic injury on early stage.

Protective effects of caffeic acid phenethyl ester against acute radiation-induced hepatic injury in rats

Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. The current study was intended to evaluate the protective effect of CAPE against the acute radiation-induced liver damage in rats. Male Sprague–Dawley rats were intraperitoneally administered with CAPE (30mg/kg) for 3 consecutive days before exposing them to a single dose of 30Gy of β-ray irradiation to upper abdomen. We found that pretreatment with CAPE significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase and increased the activity of superoxide dismutase and glutathione. Histological evaluation further confirmed the protection of CAPE against radiation-induced hepatotoxicity. TUNEL assay showed that CAPE pretreatment inhibited hepatocyte apoptosis. Moreover, CAPE inhibited the nuclear transport of NF-κB p65 subunit, decreased the level of tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthase. Taken together, these results suggest that pretreatment with CAPE offers protection against radiation-induced hepatic injury.

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MR finding of radiation-induced hepatic injury: Relationship to absorbed dose and time course after irradiation

PurposeTo evaluate if Gd-EOB-DTPA-enhanced MRI could identify liver tissue damage caused by radiation exposure in patients undergoing external beam radiation therapy. Materials and methodsWe enrolled 11 patients who underwent Gd-EOB-DTPA-enhanced MRI during or after radiotherapy in which the radiation field included the liver. External beam radiotherapy was delivered through multiple fields using a 10-MV linear accelerator. The hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI were qualitatively evaluated for the presence of a decreased uptake of Gd-EOB-DTPA in the irradiated area in the liver. Next, signal intensity (SI) ratio of the irradiated area to the non-irradiated liver parenchyma was also calculated. The absorbed dose of the irradiated area in the liver was standardized using equivalent dose in 2Gy fraction (EQD2) and biological effective dose (BED). The results of qualitative analysis were compared with EQD2 or BED, and linear regression analysis was performed between EQD2 or BED and SI ratio. ResultsTwenty-two irradiated areas were evaluated. Qualitative analysis revealed a decreased uptake of Gd-EOB-DTPA in 14 areas and no decreased uptake of Gd-EOB-DTPA in eight areas. The thresholds of EQD2 and BED causing a decreased uptake of Gd-EOB-DTPA were considered to be 24 to 29Gy and 29 to 35Gy, respectively. Quantitatively, SI ratio decreased as EQD2 or BED increased (r=0.89, p<0.001), and the inverse relationship between signal enhancement and the absorbed dose in the irradiated area was obtained. One area with EQD2 of 50Gy and BED of 60Gy showed a slightly decreased uptake of Gd-EOB-DTPA on the 40th day but a clearly decreased uptake of Gd-EOB-DTPA on the 123rd day from initiation of radiotherapy. ConclusionsGd-EOB-DTPA-enhanced MRI described RLI as a decreased uptake of Gd-EOB-DTPA matching the irradiated area. The occurrence of this finding was significantly correlated with the absorbed dose of the irradiated area in the liver.

Safety of Repeated Yttrium-90 Radioembolization

Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

Light and Electron Microscopic Investigations on the Protective Effects of Lycopene (Tomato Supplementation) Against Accumulative Low Doses of Gamma Radiation-Induced Hepatic Cellular Injury in Rats

Back ground: Antioxidants are substances that may protect our cells against the effects of free radicals. Free radicals are molecules produced when our body breaks down food, or by environmental exposures like radiation. Free radicals can damage cells. Aim: Our goal of this study is to ameliorate the damage resulted by accumulative low doses of Gamma radiation using natural antioxidant that are available to most of the people that work in the field of radiation like Lycopene that found in tomato. Materials and methods: The radio protective effect of Lycopene against liver damage was investigated in 40 male albino rats (10 per group). Group 1 rats considered normal controls, Group 2 considered irradiated group which were exposed to fractionated doses of 1/2Gy every two days for one month, Group 3 considered control group which delivered Lycopene alone (5 mg/kg per day) for two months, the last group was group 4 which considered irradiated treated animals which were given Lycopene for two months of the experiment. Animals of groups 1 and 2 were sacrificed after one month while groups 3 and 4 were sacrificed after 2 months. Samples were taken and prepared for microscopic studies. Results: Examined Sections showed that there were no cellular changes in group 2, while, a significant cellular injury was clearly observed in group 3. On the other hand Group 4 showed significant decrease in the Pathological changes occurred in compared with group 3. Conclusion: we come to the fact that Lycopene supplementation may be helpful to reduced pathological cellular injuries in the liver cells induced by accumulated doses of radiation exposure further studies may be done to confirm these findings.

Eutigoside C attenuates radiation‐induced crypt injury in the mouse intestine

On Jeju Island, South Korea, the leaves of Eurya emarginata have been traditionally used to treat ulcers or as a diuretic. Eutigoside C isolated from the leaves has been reported to have in vitro anti-inflammatory effects. We evaluated the radioprotective effects of eutigoside C on jejunal cell apoptosis and crypt survival in mice subjected to gamma irradiation. In addition, the ability of eutigoside C to protect against radiation-induced oxidative stress was examined by evaluating the activities of superoxide dismutase (SOD) and catalase (CAT) in radiation-induced hepatic injury. Eutigoside C was administered intraperitoneally at 48, 12, and 1 h before irradiation. The administration of eutigoside C (10, 50, or 100 mg/kg body weight) before irradiation protected the intestinal crypts from radiation-induced apoptosis (p < 0.05), and attenuated radiation-induced decrease of villous height (p < 0.05). Pretreating mice prior to irradiation with eutigoside C (100 mg/kg) significantly improved the survival of the jejunal crypt (p < 0.01). The dose reduction factor was 1.09 at 3.5 days after irradiation. Treatment of eutigoside C prior to irradiation significantly protected SOD and CAT activities in radiation-induced hepatic injury (p < 0.05). These results suggest that eutigoside C is a useful radioprotector capable of defending intestinal progenitor cells against indirect depletion, such as oxidative stress and inflammatory response caused by gamma irradiation.

Identification of Proteins Indicating Radiation-induced Hepatic Toxicity in Cirrhotic Rats

Radiation therapy (RT) has been emerging as one of the palliative treatments for locally advanced hepatocellular carcinoma (HCC). However, hepatic toxicity is a major obstacle in radiotherapy for HCC. The purpose of this study is to identify proteins indicating radiation-induced hepatic toxicity in cirrhotic rats, which can be used as possible biomarkers. Liver cirrhosis was induced in Wistar rats with thioacetamide (TAA) 0.3 g/L in drinking water for 9 weeks. The development of liver cirrhosis was observed histologically. Radiation hepatic injury was induced by treating 1/3 of the liver with 10 Gy single dose radiation. To find out commonly expressed proteins, liver tissue and serum were analyzed using two-dimensional electrophoresis and quadrupole time of flight mass spectrometry. Identified proteins were validated using western blotting. Histological examination showed that the degree of hepatic fibrosis increased by radiation in liver cirrhosis. It was associated with a decrease in the proliferation of cell nuclear antigen and an increase of apoptosis. The proteomic analysis of liver tissue and serum identified 60 proteins which showed significant change in expression between the TAA-alone and TAA-plus-radiation groups. Among these, an increase of heparanase precursor and decrease of hepatocyte growth factor were shown commonly in liver tissue and serum following radiation. Hepatic fibrosis increased following radiation in cirrhotic rats. These proteins might be useful in detecting and monitoring radiation-induced hepatic injury.

Biochemical metabolic changes assessed by31P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

To compare the features of biochemical metabolic changes detected by hepatic phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) with the liver damage score (LDS) and pathologic changes in rabbits and to investigate the diagnostic value of (31)P MRS in acute hepatic radiation injury. A total of 30 rabbits received different radiation doses (ranging 5-20 Gy) to establish acute hepatic injury models. Blood biochemical tests, (31)P MRS and pathological examinations were carried out 24 h after irradiation. The degree of injury was evaluated according to LDS and pathology. Ten healthy rabbits served as controls. The MR examination was performed on a 1.5 T imager using a (1)H/(31)P surface coil by the 2D chemical shift imaging technique. The relative quantities of phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. The data were statistically analyzed. (1) Relative quantification of phosphorus metabolites: (a) ATP: there were significant differences (P < 0.05) (LDS-groups: control group vs mild group vs moderate group vs severe group, 1.83 +/- 0.33 vs 1.55 +/- 0.24 vs 1.27 +/- 0.09 vs 0.98 +/- 0.18; pathological groups: control group vs mild group vs moderate group vs severe group, 1.83 +/- 0.33 vs 1.58 +/- 0.25 vs 1.32 +/- 0.07 vs 1.02 +/- 0.18) of ATP relative quantification among control group, mild injured group, moderate injured group, and severe injured group according to both LDS grading and pathological grading, respectively, and it decreased progressively with the increased degree of injury (r = -0.723, P = 0.000). (b) PME and Pi; the relative quantification of PME and Pi decreased significantly in the severe injured group, and the difference between the control group and severe injured group was significant (P < 0.05) (PME: LDS-control group vs LDS-severe group, 0.86 +/- 0.23 vs 0.58 +/- 0.22, P = 0.031; pathological control group vs pathological severe group, 0.86 +/- 0.23 vs 0.60 +/- 0.21, P = 0.037; Pi: LDS-control group vs LDS-severe group, 0.74 +/- 0.18 vs 0.43 +/- 0.14, P = 0.013; pathological control group vs pathological severe group, 0.74 +/- 0.18 vs 0.43 +/- 0.14, P = 0.005) according to LDS grading and pathological grading, respectively. (c) PDE; there were no significant differences among groups according to LDS grading, and no significant differences between the control group and experimental groups according to pathological grading. (2) The ratio of relative quantification of phosphorus metabolites: significant differences (P < 0.05) (LDS-moderate group and LDS-severe group vs LDS-control group and LDS-mild group, 1.94 +/- 0.50 and 1.96 +/- 0.72 vs 1.43 +/- 0.31 and 1.40 +/- 0.38) were only found in PDE/ATP between the moderate injured group, the severe injured group and the control group, the mild injured group. No significant difference was found in other ratios of relative quantification of phosphorus metabolites. (31)P MRS is a useful method to evaluate early acute hepatic radiation injury. The relative quantification of hepatic ATP levels, which can reflect the pathological severity of acute hepatic radiation injury, is correlated with LDS.

Gene Expression Profiles in Mouse Liver Cells after Exposure to Different Types of Radiation

The liver is one of the target organs of radiation-induced cancers by internal exposures. In order to elucidate radiation-induced liver cancers including Thorotrast, we present a new approach to investigate in vivo effects of internal exposure to alpha-particles. Adopting boron neutron capture, we separately irradiated Kupffer cells and endothelial cells in mouse liver in vivo and analyzed the changes in gene transcriptions by an oligonucleotide microarray. Differential expression was defined as more than 3-fold for up-regulation and less than 1/3 for under-regulation, compared with non-irradiated controls. Of 6,050 genes examined, 68 showed differential expression compared with non-irradiated mice. Real-time polymerase chain reaction validated the results of the microarray analysis. Exposure to alpha-particles and gamma-rays produced different patterns of altered gene expression. Gene expression profiles revealed that the liver was in an inflammatory state characterized by up-regulation of positive acute phase protein genes, irrespective of the target cells exposed to radiation. In comparison with chemical and biological hepatotoxicants, inductions of Metallothionein 1 and Hemopexin, and suppressions of cytochrome P450s are characteristic of radiation exposure. Anti-inflammatory treatment could be helpful for the prevention and protection of radiation-induced hepatic injury.

MRI study of acute radiation-induced hepatic injury with super paramagnetic iron oxide enhancement in experimental model

目的 应用家兔模型,探讨肝脏急性放射性损伤超顺磁性氧化铁(SPIO)增强MRI方法与影像表现.方法 12只成年家兔,单次40 Gy X线半肝照射后第10天,行肝脏SPIO增强前后MRI和病理学研究.结果 12只家兔增强前快速自旋回波(TSE)T2WI,2只肝脏照射区呈稍高信号,1只呈稍低信号.SPIO增强多序列MRI共检出9只阳性家兔,肝脏照射区表现为相对高、较高信号,以快速场回波(TFE)T1WI检出率最高.200倍光学显微镜下,家兔肝脏照射区均出现不同程度小叶中央静脉血管闭塞性损伤;肝脏透射电子显微镜检查发现照射区肝脏细胞水肿、胶原纤维沉积、胞质内空泡化和Disse间隙水肿等异常.结论 肝脏受单次大剂量照射后早期病理以小叶中央静脉血管闭塞性损伤为主要特征,SPIO增强MRI是评价肝脏急性放射性损伤的有效手段。

The triple-phase CT image appearance of post-irradiated livers.

To evaluate the sequential CT appearance of the liver after hepatic irradiation and to investigate the correlation between CT findings and radiation-induced hepatic injury. The triple-phase CT images of 18 patients with hepatocellular carcinomas (HCC) after hepatic irradiation were retrospectively reviewed (in total 41 CT studies). The high-dose region within the liver was defined as the area receiving more than 90% of the prescribed irradiation dose. The mean radiation dose was 55.5 Gy. Density changes and patterns of enhancement in the high-dose region were classified as three types: type I, constant low-density change in all phases; type II, low-density change in both pre-contrast and arterial phases, and iso-density change in the portal phase; type III, low- or iso-density change in the pre-contrast phase, low- or high-density change in the arterial phase, and persistent high-density change in the portal phase. The interval between completion of radiotherapy and the CT examinations ranged from 9 to 469 days, with a mean of 147 days. Nine of the 41 CT studies presented with type I, 9 with type II, and 16 with type III CT findings. The mean interval between completion of radiotherapy and the appearance of types I, II, and III CT findings were 74, 183, and 220 days, respectively. The interval was significantly shorter for type I findings than for type II and type III. The difference in interval was not significant between type II and type III. A type I finding with constant low-density change in the high-dose region of the liver was the most common pattern of CT findings within the first 3 months after hepatic irradiation. Either types II or III findings were frequently seen after 3 months. The sequential CT appearance and the density changes may indicate correlation with the pathogenesis of veno-occlusive disease.

Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging

The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T 2-, T 1-weighted imaging and Gd-DTPA enhanced dynamic studies. T 2 relaxation times, signal intensity ratios in T 1-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T 1-WI and hyperintense in T 2-WI. T 2 values and signal intensity ratios in the T 1-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.

CT evaluation of hepatic injury following proton beam irradiation: appearance, enhancement, and 3D size reduction pattern.

The purpose of this study was to investigate the long-term imaging appearances of hepatic injury following proton beam irradiation. The time-attenuation curves, time of appearance and recovery, and 3D size reduction pattern are described in patients of different ages and genders with different irradiation doses, irradiated portals, and Child groups. Forty-six patients with hepatocellular carcinoma underwent 50 to 84 Gy proton beam irradiation in periods of 14-52 days. CT including noncontrast and dynamic study was performed every 3 months starting 3 weeks after the end of irradiation. The 3D volume measurement of areas of radiation-induced hepatic injury was performed through incremental dynamic CT images in every follow-up study. CT follow-up study of the patients was done for 12-76 months. Radiation-induced hepatic injury was observed as low attenuation areas on noncontrast CT and enhanced areas on dynamic study in the regions corresponding to the irradiation portals. Of our cases, 67.5% showed the appearance of radiation hepatitis in 3-4 weeks and 95.3% in 3-4 months after the end of irradiation. In both periods, there was a significant delay in the female patients. The time-attenuation curve showed an early and prolonged enhancement of the irradiated regions. The volume reduction pattern of the injured areas was found to be longstanding, exponential, and directed from periphery to the center. Early appearance of radiation-induced hepatic injury was found only to be gender dependent, with a tendency to occur with higher irradiated doses; no other parameters affected this phenomenon in our cases. Disappearance of the injured areas, if present, takes a long time (at least 42 months).

The Ultrasound Appearance of Radiation-Induced Hepatic Injury

The Ultrasound Appearance of Radiation-Induced Hepatic Injury

Hepatic Injury after Whole-Liver Irradiation in the Rat

Radiation-induced hepatic injury in rats, which is characterized by marked ascites accompanied by liver necrosis, fibrosis, and vein lesions, is described in this study. These adverse sequelae are produced within 30 days after irradiation if there is surgical removal of two-thirds of the liver immediately after whole-liver irradiation. The LD50/30 day and median survival time after liver irradiation and two-thirds partial hepatectomy is 24 Gy and 17 days, respectively. Death is preceded by reduction in liver function as measured by [131I]-labeled rose bengal clearance. Prior to death, liver sepsis and endotoxemia were detected in most irradiated, partially hepatectomized animals. Pretreatment of the animals with endotoxin and/or antibiotic decontamination of the GI tract, which increase the host resistance to infection and endotoxemia, resulted in increased survival time, but no irradiated, partially hepatectomized animal survived beyond 63 days. The combination of these treatments resulted in additive effects leading to 38% survival at 100 days. These treatments did not, however, prevent the eventual development of radiation-induced liver pathology. This suggests that sepsis and endotoxemia resulting from the bacteria in the intestine are the immediate cause of death after 30-Gy liver irradiation and partial hepatectomy. It is concluded that the hepatectomized rat model is an economical and scientifically manageable experimental system to study a form of radiation hepatitis that occurs in compromised human livers.