Radiation-induced Liver Damage Research Articles

Current Insights into Molecular Mechanisms and Potential Biomarkers for Treating Radiation-Induced Liver Damage.

Highly conformal delivery of radiation therapy (RT) has revolutionized the treatment landscape for primary and metastatic liver cancers, yet concerns persist regarding radiation-induced liver disease (RILD). Despite advancements, RILD remains a major dose-limiting factor due to the potential damage to normal liver tissues by therapeutic radiation. The toxicity to normal liver tissues is associated with a multitude of physiological and pathological consequences. RILD unfolds as multifaceted processes, intricately linking various responses, such as DNA damage, oxidative stress, inflammation, cellular senescence, fibrosis, and immune reactions, through multiple signaling pathways. The DNA damage caused by ionizing radiation (IR) is a major contributor to the pathogenesis of RILD. Moreover, current treatment options for RILD are limited, with no established biomarker for early detection. RILD diagnosis often occurs at advanced stages, highlighting the critical need for early biomarkers to adjust treatment strategies and prevent liver failure. This review provides an outline of the diverse molecular and cellular mechanisms responsible for the development of RILD and points out all of the available biomarkers for early detection with the aim of helping clinicians decide on advance treatment strategies from a single literature recourse.

Prognostic analysis of radiation-induced liver damage following carbon-ion radiotherapy for hepatocellular carcinoma

BackgroundRadiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT.MethodsWe retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child–Pugh score within 12 months following CIRT. The median age of the patients was 76 years (range 47–95 years), and the median tumor diameter was 41 mm (range 5–160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child–Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range 2.3–41.1 months), and RILD was observed in 11 patients (10.1%).ResultsMultivariate analysis showed that pretreatment Child–Pugh score B (p = 0.003, hazard ratio [HR] = 6.90) and normal liver volume spared from < 30 Gy RBE (VS30 < 739 cm3) (p = 0.009, HR = 5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child–Pugh class A or B and VS30 < 739 cm3 or ≥ 739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively.ConclusionIn conclusion, the pretreatment Child–Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC.

Protective effect of intermittent hypobaric hypoxia against radiation-induced liver damage in Sprague-Dawley rats.

Without timely and effective interventions or treatments, radiation-induced liver damage (RILD) can lead to serious consequences for the patients and their families. To investigate the protective effect of intermittent hypobaric hypoxia preconditioning (IHHP) in RILD. Male adult SD rats were randomly divided into 8 groups including one control group, one only irradiation group and other experimental groups. Blood routine tests and liver function tests were all assessed with abdominal venous blood. Moreover, hematoxylin eosin (HE) staining and immunohistochemistry assay were used to detect the histopathological changes and expressions of transforming growth factor-β1 (TGF-β1), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1α (HIF-1α) in radiated liver sections. Blood routing tests showed that RBC, WBC and Hb were all significantly increased while the differences of these results between different groups with same simulated altitude were approximate. However, liver function in the IHHP plus irradiation at 4000 m group was significantly decreased (P< 0.05) compared to only irradiation groups, and the manifestation of HE and lower positive expression of TNF-α showed improved histopathological changes in the liver section. Furthermore, no significant difference of HIF-1α expression between any two groups treated with IHHP was observed. IHHP at the altitude of 4000 m group could alleviate the radioactive liver damage by downregulating TNF-α and less strong positive expression of TGF-β1. Furthermore, patients exposed to radiation might benefit from this treatment to prevent or reduce the RILD.

MiR-146a-5p Alleviates Radiation-Induced Liver Fibrosis by Regulating PTPRA-SRC Signaling in Mice.

Patients with hepatobiliary tumors who accept radiotherapy are at risk for radiation-induced liver fibrosis. MicroRNAs (miRNAs) have been implicated in the pathogenesis of radiation-induced liver damage and possess potential as novel biomarkers and therapeutic targets. However, the role of miR-146a-5p in radiation-induced liver fibrosis is less well understood. The current study was designed to evaluate the role of miR-146a-5p in radiation-induced liver fibrosis in mice and to investigate the possible mechanisms involved in miR-146a-5p-mediated effects. The experiments were performed on Institute of Cancer Research (ICR) mice which received fractionated radiation (30 Gy in 5 fractions) to the liver. The results show radiation could induce histopathological changes, liver dysfunction and fibrosis accompanied with decreased miR-146a-5p expression. miR-146a-5p agomir treatment resulted in recovery of liver function and reduced the amount of alpha-smooth muscle actin (α-SMA), collagen 1, protein tyrosine phosphatase receptor type A (PTPRA) and phosphorylated SRC in the livers of irradiated mice. Therefore, our study reveals that miR-146a-5p inhibits the progression of hepatic fibrosis after radiation treatment. And the beneficial role of miR-146a-5p may be relevant to PTPRA-SRC signaling pathway.

Comparative dosimetric study of spot-scanning proton therapy versus volumetric-modulated radiation therapy for extrahepatic bile duct cancer

This study aimed to compare the dose distributions and clarify the dosimetric characteristics of spot-scanning proton therapy (SSPT) and photon volumetric modulated arc therapy (VMAT) for extrahepatic bile duct cancer (EBDC). This retrospective study included 10 patients with EBDC treated with real-time image-gated SSPT. Using the simultaneous integrated boost technique, the 2 prescription dose levels for planning target volumes were 72.6 and 44 Gy, delivered in 22 fractions. Plan quality comparisons were conducted by analyzing various parameters, including homogeneity, conformity, dose to organs at risk, and normal tissue complication probability (NTCP) for radiation-induced liver damage (RILD). The target dose distributions using SSPT were almost equivalent to those achieved using photon VMAT. There was a significant reduction in all liver dose parameters, the NTCP value for RILD, and kidney dose (mean, V12 Gy, and V18 Gy) in SSPT than in photon VMAT. No significant differences were observed in the intestinal doses in the high-dose area. Thus, compared with photon VMAT, SSPT for EBDC significantly reduced radiation doses to the liver and kidneys and has shown potential clinical benefits of reduced radiation-induced toxicity.

Abstract 2417: Liver regeneration after radiation therapy: clinical observations and a new rat model

Abstract Background and Purpose: Radiation-induced liver damage, a dose-limiting complication of radiotherapy for liver tumors, has been focused mainly on prevention and treatment but has largely ignored the molecular mechanisms underlying the liver’s regenerative capacity after irradiation. Whether liver regeneration compensates for radiation-induced liver damage is of great clinical significance. This study aims to observe clinical liver regeneration and the potential molecular mechanism in rat models after irradiation. Methods: To stimulate the liver regeneration response, we delineated a liver protection area in the patient’s normal liver to protect it from excessive irradiation, and designed a rat model in which large single fractions of 25 Gy or 15 Gy of radiation were delivered to 1/2 or 2/3 of the total liver volume to investigate liver regeneration after irradiation. We used proteomics analysis and western blotting assays to investigate liver regeneration signaling and molecular mechanisms. Results: Four patients’ pairs of liver specimens from areas of high irradiation and regeneration (protected liver) were collected. Proteomics analysis showed enrichment in several pathways, with some of the greatest changes observed in PI3K-Akt signaling, further confirmed in liver-irradiated rat models. After irradiation, the liver injury index was significantly elevated on day-1 and gradually recovered to normal levels by day-8 in rat models. The model of a single 25-Gy fraction delivered to half of the liver volume best represented the clinically similar phenomenon of liver regeneration in the protected liver. We tested the effects of an Akt/mTOR activator (carbamazepine), which enhanced regeneration, and an Akt/mTOR inhibitor (temsirolimus), which inhibited regeneration. Finally, liver regeneration was enhanced in rats treated with temsirolimus followed by carbamazepine. Conclusions: Our results suggest that protecting the normal liver outside the irradiated area enhances the probability of successful regeneration to compensate for radiation-induced liver injury. PI3K/AKT/mTOR is essential in liver regeneration after irradiation, and carbamazepine may enhance liver regeneration after irradiation in rats. Citation Format: Tingshi Su, Weidong Zhao, qing Li, Qiaoyuan Wu. Liver regeneration after radiation therapy: clinical observations and a new rat model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2417.

Aloe vera gel as a stimulant for mesenchymal stem cells differentiation and a natural therapy for radiation induced liver damage

Aloe vera is a medical plant that has been used, traditionally, in treatment of several dermal disorders. In addition to its role as an anti-cancer, anti-oxidant, anti-diabetic, and anti-hyperlipidemic agent. Aloe vera gel extract contains several compounds like minerals, enzymes, hormones and carbohydrates. Therefore, Aloe vera as well as its bioactive constituents have been studied to determine its intriguing potential roles in medicinal science. Mesenchymal stem cells (MSCs) are biologically active precursor cells that can self-renew and develop into a variety of cell types. Plant extracts have been used, in vitro, to enhance the proliferation and differentiation of MSCs. Therefore, the present study aimed to evaluate the therapeutic effect of lyophilized Aloe vera gel together with bone marrow (BM)-MSCs transplantation against radiation induced liver damage (RILD) in X-ray irradiated Sprague dawley male rats. By determining the oxidative stress, antioxidant enzymes, and pro-inflammatory cytokines in liver tissue homogenate, the antioxidant and anti-inflammatory properties of lyophilized Aloe vera gel were investigated. The degree of liver damage and NF-κB expression were determined using histological and immunohistochemical staining techniques. The results showed that treatment of irradiated rats with lyophilized Aloe vera gel and MSCs transplantation has led to an improvement in liver function and a decrease in fibrotic markers, oxidative stress, and pro-inflammatory cytokines; as well as, a reduction in the pathological alterations in the rats' liver and a reduced NF-κB activation. Lyophilized Aloe vera gel provided two important functions; where it stimulated the differentiation of transplanted MSCs and alleviated the radiation induced damages in liver. Aloe vera's antioxidant and anti-inflammatory properties have enhanced liver function, as well as, creating a favorable environment for MSCs development in the liver. MSCs, in combination with lyophilized Aloe vera gel, hold promise for regenerative medicine; where, it has a considerable impact on MSCs differentiation.

Amelioration of radiation-induced liver damage by p-coumaric acid in mice

Radiation-induced liver damage (RILD) is a spiny problem in radiotherapy or other circumstances that exposure to radiation. The need for radioprotective agent is increasing to protect liver tissue. This study aimed to explore the hepatoprotective effect of p-coumaric acid (CA) against RILD. C57BL/6 male mice were exposed to 4 Gy irradiation and administrated with CA for 4 days starting on the same day of irradiation. Mice were sacrificed to obtain blood and liver tissues on day 3.5 or 14 post irradiation, respectively. The blood and liver tissues were collected. As compared with the only irradiated group, CA supplementation improved liver morphology, decreased serum alanine aminotransferase and aspartate aminotransferase, inhibited BCL2-associated X (BAX) protein expression, and improved the mice hematopoietic function. CA at the dose of 100 mg/kg body weight showed better effect compared to the other doses. Thus, CA might possess potential to protect against RILD.

Radiation Induced Liver Injury: Collateral Damage Radiologically Simulating Interval Metastasis in Carcinoma Esophagus; a Diagnostic Dilemma Resolved Through Liver Biopsy.

F-18-fluorodeoxyglucose positron emission tomography (18-FDG PET/CT) is increasingly being used in patients with cancer, both for baseline staging and for evaluation of treatment response. However, in patients with incidental irradiation of the liver during radiotherapy, particularly for lower gastrointestinal tract cancers, increased focal F-18-fluorodeoxyglucose positron emission tomography avidity may be the result of collateral radiation induced liver damage rather than metastases. Awareness of this pathologic entity and correlation with with other imaging, clinical and laboratory findings including liver biopsy is vital to avoid misinterpretation and overstaging of the carcinoma in these patients. We encountered such a scenario in an elderly female patient with distal esophageal squamous cell carcinoma patient, who developed F-18-fluorodeoxyglucose positron emission tomography avid left lobe liver lesion post neoadjuvant radiotherapy, simulating interval metastasis. A liver biopsy ruled out malignancy and helped to clinch the correct diagnosis of radiation induced liver injury.

Hepatotoxicity and renal toxicity induced by radiation and the protective effect of quercetin in male albino rats

Purpose Although radiation is one of the basic methods commonly used in cancer treatment, it inevitably enters the field of treatment in healthy tissues and is adversely affected by the acute and chronic side effects of radiation. This study evaluated the possible protective effects of quercetin, an antioxidant agent, against liver and kidney damage in rats exposed to a whole-body single dose of radiation (10 Gy of gamma-ray). Materials and methods The study groups were formed as control, sham, quercetin, radiation, quercetin + radiation and radiation + quercetin using 60 male Wistar albino (200–250 g, 3 months old) rats, including 10 rats in each group. The gamma-ray provided by the Co60 teletherapy machine was given to the whole body as external irradiation. According to the groups, quercetin was administered to rats at 50 mg/kg/day via oral gavage before or after radiation administration. The rats were sacrificed the day after irradiation and the extracted tissue samples from all groups were compared histologically and immunohistochemically. DNA damage was determined by the neutral comet assay technique. Also, malondialdehyde (MDA) and glutathione peroxidase (GSH) were evaluated in liver and kidney tissues by the ELISA method. Results Histopathological changes were observed altered morphology of liver and kidney tissues in the radiation groups. Sinusoidal dilatations, vacuolization, and hepatic parenchyma necrosis in the liver, while in kidneys, glomerular shrinkage, widened Bowman’s space, tubular dilatation, and inflammation were evident. TNF-α, IL1-α, HIF1-α, and caspase 3 immunoreactivities in tissues were determined by immunohistochemistry. High caspase 3 positive cell number confirmed apoptosis, the comet parameters were decreased in the quercetin + radiation group. When compared to the control group, the exposure to radiation showed a marked elevation in MDA which was accompanied by high GSH. This damage was reduced in the quercetin + radiation group. Conclusions With the results obtained from the study; Quercetin is thought to have a protective potential against radiation-induced liver and kidney damage due to its radioprotective effect.

A new lightweight convolutional neural network for radiation-induced liver disease classification

Histopathological image analysis is used in the diagnosis of many diseases such as cancer, brain tumor, fatty liver and congenital heart diseases. In clinical practice, the time-consuming diagnostic process requires an expertise in the field, and disagreements can arise among pathologists at the decision stage. Machine learning methods can be used in diagnostic stage to overcome these issues. Especially, the use of deep learning systems in the analysis of histopathological images can reduce the workload of pathologists and can provide more objective results. Over traditional machine learning methods using handcrafted features, deep learning approaches that can automatically learn features stand out with their performance in the analysis of histopathology images. In this paper, we propose a patch-based lightweight convolution neural network for histopathological image classification for detecting radiation-induced liver damage. The proposed model was trained to classify the radiation-induced liver disease dataset comprising 555 histopathological images. An accuracy of 100% for binary classification and an accuracy of 87.57% for multi-class classification were achieved on the unseen test set. Our model outperforms state-of-the-art models, including ResNet-50, AlexNet, Vgg16, and GoogleNet. This paper is the first to classify radiation-induced liver disease data with deep learning, and it can be a promising tool for diagnosis purpose of pathologists. Since it is vital to detect a damage that leads to deteriorating liver function, this study is valuable in the field of medicine.

Curcumin protects radiation-induced liver damage in rats through the NF-\u03baB signaling pathway

BackgroundCurcumin has been demonstrated to exert anti-oxidant, anti-fibrotic, anti-inflammatory, and anti-cancer activities. This study was conducted to observe the effect and inner mechanism of curcumin in rats with radiation-induced liver damage (RILD).MethodsThirty SD rats were classified into Control, Radiation group and Curcumin (Cur) + Radiation group (n = 10 in each group). The changes in body weight of the rats were observed on the 3rd, 7th and 14th days after the treatment with curcumin. On the 14th day post treatment, the heart blood of the rats was drawn for measurement of liver function indices including total protein (TP), alanine aminotransfetase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) as well as aspartate aminotransfetase (AST). Subsequently, the rats were euthanized and liver tissues were taken to observe liver morphological changes using hematoxylin-eosin (HE), and to analyze apoptosis condition using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assays. Meanwhile, the oxidative stress level in liver tissue homogenate was determined by biochemical analysis. The expression of nuclear factor kappa B (NF-κB) pathway-associated and apoptosis-associated proteins was detected using Western blot analysis, and the expression levels of inflammatory factors were measured by Enzyme-linked immunosorbent assay (ELISA).ResultsThe reduced body weight was observed in rats of the Radiation group compared to the Control and Cur + Radiation groups on day 14. In the Radiation group, hepatic cell edema and inflammatory cell infiltration could be visible under the light microscope, and the hepatocytes presented with vacuolar degeneration. In the Cur + Radiation group, the hepatocytes swelled under the microscope, but the pathological changes were alleviated in comparison with the Radiation group. RILD rats with curcumin treatment presented with decreased ALT, AST, ALP, LDH, and maleicdialdehyde (MDA) levels, and elevated TP, superoxide dismutase (SOD), caspase activated DNase (CAD) and glutathione (GSH) levels. Apoptosis and inflammation in rats with RILD were up-regulated, and the NF-κB pathway was activated, but they were reversed after continuously intragastric administration of curcumin for 14 days.ConclusionOur study highlights that curcumin treatment reduces the liver damage caused by radiation through the inhibition of the NF-κB pathway.

Evaluating dose constraints for radiation induced liver damage following magnetic resonance image guided Stereotactic Body radiotherapy

This study reports dose corresponding to visible radiation induced liver damage following Stereotactic Body Radiation Therapy (SBRT) for liver metastasis, and the optimal time for follow up scans using post radiation imaging. Diagnostic magnetic resonance scans of nine patients treated with liver SBRT using a 0.35 T MRI-guided radiotherapy system were analyzed. The dice coefficients between the region of visible liver damage and the delivered dose were calculated. A median dose of 35 Gy correlated most closely with the visible radiation induced liver damage. We compared scans over two to nine months and observed maximal dice coefficients at two to five months post radiation. We have presented a new method for developing treatment planning guidelines for liver SBRT.

Clinical application of advances and innovation in radiation treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) management has evolved over the past two decades, with the development of newer treatment modalities. While various options are available, unmet needs are reflected through the mixed treatment outcome for intermediate-stage HCC. As HCC is radiosensitive, radiation therapies have a significant role in management. Radiation therapies offer local control for unresectable lesions and for patients who are not surgical candidates. Radiotherapy also provides palliation in metastatic disease, and acts as a bridge to resection and transplantation in selected patients. Advancements in radiotherapy modalities offer improved dose planning and targeted delivery, allowing for better tumor response and safer dose escalations while minimizing the risks of radiation-induced liver damage. Radiotherapy modalities are broadly classified into external beam radiation therapy and selective internal radiation therapy. With emerging modalities, radiotherapy plays a complementary role in the multidisciplinary care of HCC patients. We aim to provide an overview of the role and clinical application of radiation therapies in HCC management. The continuous evolution of radiotherapy techniques allows for improved therapeutic outcomes while mitigating unwanted adverse effects, making it an attractive modality in HCC management. Rigorous clinical studies, quality research and comprehensive datasets will further its application in the present era of evidence-based practice in Medicine.

Therapeutic effect of phycocyanin on acute liver oxidative damage caused by X-ray

1) BackgroundPhycocyanin (PC) is a type of natural protein in algae with antioxidant and anti-inflammatory properties. However, the protective effect of PC on hepatic damage induced by X-ray remains unknown. 2) MethodsMale C57BL/6 mice were gavaged with 200mg/kg PC for consecutive 7 days before or after radiation. The blood samples and tissues were collected on days 1 and 7 after radiation exposure. 3) ResultsPretreatment or treatment with PC decreased significantly the levels of alanine aminotransferase (ALT), aspartate aminotransferase(AST) in the plasma. Histological evaluation further confirmed the protection of PC against radiation-induced hepatotoxicity. PC-treatment also increased the relative mRNA expression of superoxide dismutase (SOD) and glutathione (GSH-PX), and descended the ROS in the liver. Moreover, the expression of H2AX, an indicator of DNA damage in mice, of the PC-intervention group was much smaller than that of the radiation group. In vivo, PC-treatment markedly up-regulated NF-E2-related factor 2(Nrf2) expression and downstream gene such as hemeoxygenase-1 (HO-1), NQO1. 4) Conclusion: PC could attenuate the radiation-induced oxidative stress damage by activating Nrf2/ HO-1 signaling pathway, and reduce the radiation-induced DNA damage. Therefore, PC is a protective agent against radiation-induced liver damage.

Phantom simulation of liver metastasis on a positron emission tomography with computed tomography scan after neoadjuvant chemoradiotherapy for distal esophageal cancer: a case report

BackgroundNeoadjuvant chemoradiotherapy is currently the gold standard treatment for esophageal cancer prior to surgery. This radiation therapy will sometimes lead to liver damage parallel to esophageal lesions, which mimics liver metastasis visualized by 18F-fluorodeoxyglucose positron emission tomography with computed tomography. In this report, we publish virtual radiation-induced liver damage images obtained during surgery, along with the coherent pathology, in order to confirm the false-positive result through an optimally decisive radiological examination.Case presentationWe report a case of a Asian male patient with distal esophageal cancer who had undergone neoadjuvant chemoradiotherapy (5000 cGy). Subsequently, a new lesion was discovered during a positron emission tomography with computed tomography scan 6 weeks later, near the left caudate lobe of the liver during tumor restaging. To exclude the possibility of liver metastasis, serial imaging was conducted, which included liver sonography, computed tomography, and magnetic resonance imaging for a more intimate probe. The patient’s condition was verified as being liver inflammation change, as seen by the liver magnetic resonance imaging presentation. Thoracoscopic esophagectomy was performed with cervical esophagogastrostomy via the retrosternal route, along with a feeding jejunostomy. The procedure was performed smoothly, with an intraoperative liver biopsy also being conducted 2 weeks later, after positron emission tomography with computed tomography restaging. The pathology report revealed esophageal cancer in the form of poorly differentiated squamous cell carcinoma, pT3N1M0. The liver biopsy revealed obvious inflammation change after radiation therapy, which elucidated sinusoidal congestion with the attenuated hepatic cords and filled with erythrocytes. There was no evidence of liver metastasis. The patient recovered uneventfully and was discharged with his oral intake performing smoothly, and a stable condition was observed during 12 months of outpatient department follow-up.ConclusionsNew foci of increased 18F-fluorodeoxyglucose avidity are commonly seen in the caudate and left hepatic lobes of the liver during neoadjuvant chemoradiation for distal esophageal cancer, and these findings generally reflect radiation-induced liver disease rather than metastatic disease. Awareness of the pitfalls of a high 18F-fluorodeoxyglucose uptake in radiation-induced liver injury is crucial in order to avoid misinterpretation and overstaging. Except for the location of 18F-fluorodeoxyglucose uptake, the shape of the lesion, and an maximum standardized uptake value (> 10/h), a convincing liver magnetic resonance imaging scan or even a liver biopsy can provide accurate information for distinguishing radiotherapy-induced liver injury from liver metastasis.

Application of quantitative analysis of contrast-enhanced ultrasonography in the evaluation of acute radiation-induced liver damage.

The aim of the present study was to evaluate the microcirculation perfusion in patients with acute radiation-induced liver damage (RILD) and explore the feasibility of non-invasive evaluation of RILD using quantitative analysis of contrast-enhanced ultrasound (CEUS). Patients who successfully underwent three-dimensional conformal intensity-modulated radiotherapy for abdominal tumors were selected. CEUS was performed on the liver prior to and 2, 3 and 4 weeks after exposure, and the time-intensity curve (TIC) was obtained by quantitative analysis of CEUS. The time to peak (TTP), gradient (Grad) and area under the curve (AUC) were analyzed offline. The Grad of the CEUS TIC was decreased and TTP increased with the prolongation of the irradiation duration, with statistically significant differences between the values in the 2-, 3- and 4-week groups vs. those prior to exposure (P<0.05), as well as among the values of the 2-, 3- and 4-week groups (P<0.05). Following irradiation, the AUC decreased gradually in the 2- and 3-week groups and increased in the 4-week group, with statistically significant differences compared with the AUC prior to irradiation (P<0.05). The quantitative analysis parameters of CEUS may be important reference parameters for the early diagnosis of acute RILD.

Protective effect of different doses of pycnogenol extract against gamma radiation-induced liver damage in rat

Protective effect of different doses of pycnogenol extract against gamma radiation-induced liver damage in rat

Protective effects of hesperidin on ionizing radiation-induced liver damage

Aim: Liver is mostly exposed to radiation during radiotherapy to the upper abdomen, the right lobe of the lung, distal esophagus tumors or total body irradiation. Radiation may lead to cellular damage, and clinical and laboratory findings of liver dysfunction. This study aimed to investigate the protective effect of peroral hesperidin on reducing oxidative stress in liver tissue caused by ionızing radiation Material and Methods: 24 adult male rats were randomly divide into four groups. Group control was given only physiological saline, Group HES was given hesperidin at 50 mg/kg body weight (BW) for 15 days, Group RAD was given only irradiation, and Group HES+RAD was given hesperidin at 50 mg/kg BW daily and then irradiated. At the end of 15 hesperidinin days, the animals in Groups RAD and HES+RAD were exposed to a dose of 10 Gy to the abdominopelvic region. Liver and blood samples were used for determination of total antioxidant status (TAS) and malondialdehyde (MDA) and also histopathological examination was performed.Results: Compared with the Group RAD, the plasma and tissue MAD level was significantly decreased in Group HES+RAD (p=0.002). Both plasma and tissue levels of TAS was found significantly higher in HES+RAD group (respectively, p=0.002,p=0.004). Histological examination of Group RAD, portal edema, significant intra-cytoplasmic vacuolization, swelling in the hepatocytes, necrosis, significant sinusoidal and central vein dilation and congestion were observed . In group HES+RAD periportal edema, central vein dilation and congestion were not histologically evident when compared with Group RAD. Conclusion: Radiotherapy was found to lead to an increase in lipid peroxidation and a reduction in anti-oxidant capacity; 50 mg/kg/day hesperidin administration for 15 consecutive days was seen to reduce the histological changes of liver damage and oxidative stress in rats

Non-Invasive Targeted Hepatic Irradiation and SPECT/CT Functional Imaging to Study Radiation-Induced Liver Damage in Small Animal Models.

Radiation therapy (RT) has traditionally not been widely used in the management of hepatic malignancies for fear of toxicity in the form of radiation-induced liver disease (RILD). Pre-clinical hepatic irradiation models can provide clinicians with better understanding of the radiation tolerance of the liver, which in turn may lead to the development of more effective cancer treatments. Previous models of hepatic irradiation are limited by either invasive laparotomy procedures, or the need to irradiate the whole or large parts of the liver using external skin markers. In the setting of modern-day radiation oncology, a truly translational animal model would require the ability to deliver RT to specific parts of the liver, through non-invasive image guidance methods. To this end, we developed a targeted hepatic irradiation model on the Small Animal Radiation Research Platform (SARRP) using contrast-enhanced cone-beam computed tomography image guidance. Using this model, we showed evidence of the early development of region-specific RILD through functional single photon emission computed tomography (SPECT) imaging.