Heart Toxicity Research Articles

A dosimetric and robustness analysis of proton arc therapy with early energy layer and spot assignment for lung cancer versus conventional intensity modulated proton therapy.

Intensity Modulated Proton Therapy (IMPT) faces challenges in lung cancer treatment, like maintaining plan robustness for moving tumors against setup, range errors, and interplay effects. Proton Arc Therapy (PAT) is an alternative to maintain target coverage, potentially improving organ at risk (OAR) sparing, reducing beam delivery time (BDT), and enhancing patient experience. We aim to perform a systematic plan comparison study between IMPT and energy layer (EL) and spot assignment algorithm - Proton Arc Therapy (ELSA-PAT) to assess its potential for lung cancer treatment. A total of 14 Lung ELSA-PAT plans were compared retrospectively with IMPT plans. 4D worst-case minimax robust optimization was performed, including 84 scenarios (3%, 3 mm). Dosimetry assessment included target (clinical tumor volume [CTV]) and important OARs, on nominal and worst-case scenarios. Most relevant normal tissue complication probabilities (NTCP), target coverage robustness against interplay effect, and BDT were evaluated. CTV D95% and D98% showed no significant difference in comparison. PAT demonstrated better conformality by 66% (p = 0.00012) but delivered a higher heart mean dose (HMD, 23%). There was a 2% increase in NTCP 2-year mortality risk with PAT. Total BDT was comparable among techniques. IMPT was more robust than PAT against interplay effect, considering both D1% (1.0 ± 0.8 Gy vs 1.1 ± 1.4 Gy) and D98% bandwidths (0.9 ± 0.9 Gy vs 1.1 ± 1.3 Gy). Both techniques provide a similar level of dose coverage to the target volume. Although PAT improved dose conformality, higher HMD translated into increased heart toxicity, presumably due to chosen planning methodology and OAR proximity to target. Increased ELs and spots raised PAT BDT, although it could improve daily treatment workflow.

Perfluorodecanoic acid induces the increase of innate cells in zebrafish embryos by upregulating oxidative stress levels

Several studies reported that the widespread use of perfluoroalkyl and polyfluoroalkyl substances (PFASs) causes increased environmental pollution, subsequently impacting aquatic organisms. Perfluoroalkyl substances such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) reportedly cause cardiotoxicity, neurotoxicity, and developmental toxicity in different organisms. However, whether perfluorodecanoic acid (PFDA), a widely used perfluoroalkyl substance, induces animal embryos developmental toxicity remain unknown. Here, we explored the immunotoxicity and associated mechanisms of PFDA in zebrafish embryos via RNA sequencing, morphological assessment and behavioral alteration detection following exposure to 0.5, 1 and 2 mg/L of PFDA. Interestingly, We found that with the increase of PFDA to drug concentration, including neutrophils and macrophages, significantly increased the number of inherent cells, immune related genes expression. Furthermore, oxidative stress increased in the PFDA-treated embryos in a dose-dependent manner and inhibition of oxidative stress levels effectively rescued the number of neutrophils. Changes in embryonic behavior were observed after exposure to PFDA. Overall, our results suggest that PFDA may induce innate immune response by accumulation of oxidative stress in zebrafish at early developmental stages, and concern is needed about its environmental exposure risks for animals embryos development. Environmental implicationPerfluorinated and polyfluorinated alkyl substances (PFASs) are a class of synthetic organic compounds containing fluorine widely used as lubricants, surfactants, insecticides, etc. The PFDA, a typical perfluorinated compound, is often used as a wetting agent and flame retardant in industries.Several studies showed that PFASs can cause serious environmental pollution, leading to developmental toxicity to various animals, including reproductive toxicity, liver toxicity, heart toxicity, neurotoxicity, and immunotoxicity.However, there are still limited studies on the effects and mechanisms of PFDA on aquatic organisms. Therefore, there is a need to evaluate the ecological risks of PFDA in animals.

Mitigating Doxorubicin-Induced Cardiotoxicity through Quercetin Intervention: An Experimental Study in Rats.

Doxorubicin (DOX) is an effective anticancer drug, but its use is limited by dose-dependent heart toxicity. Quercetin is a natural antioxidant frequently studied for its beneficial properties. Moreover, a wide range of dietary supplements are available for human use. This in vivo study aimed to explore the potential cardioprotective effects of quercetin in chronic DOX treatment. A total of 32 Wistar rats were randomly divided into four groups: control, DOX, DOX/Q-50, and DOX/Q-100, treated with saline, 2.5 mg/kg body-weight DOX, 2.5 mg/kg body-weight DOX + 50 mg quercetin, and 2.5 mg/kg body-weight DOX + 100 mg quercetin, respectively, for two weeks. Rats were monitored using cardiac ultrasound (US) and markers for cardiac injury. Oxidative damage and ultrastructural changes in the heart were investigated. Chronic DOX treatment led to a decline in cardiac function and elevated values of NT pro-BNP, troponin I, and CK-MB. Quercetin treatment slightly improved certain US parameters, and normalized serum NT pro-BNP levels. Furthermore, DOX-induced SOD1 depletion with consequent Nrf2 activation and DNA damage as shown by an increase in γH2AX and 8HOdG. Quercetin treatment alleviated these alterations. Oral administration of quercetin alleviated serum markers associated with DOX-induced cardiotoxicity. Furthermore, it exhibited a favorable impact on the cardiac US parameters. This suggests that quercetin may have potential cardioprotective properties.

Homeostatic changes of trace elements in diazinon toxicity in rat model: The beneficial role of resveratrol

Background and objectivesDiazinon (DZN) is a cholinesterase inhibitor widely used to relieve agricultural pests and upgrade the productivity of crops. Resveratrol (Res), as a phenolic plant compound, has a protective role against free radicals. This study intended to evaluate the impacts of Res on homeostatic disturbances induced by DZN in rats. MethodTwenty-four Wistar rats (4 weeks) were randomly distributed into four groups of six animals each. The first group (control group) received corn oil. The second group (Res group) received orally Res (20 mg/kg. The third group (DZN group) received the oral DZN (70 mg/kg); the fourth group (Res plus DZN group) was treated simultaneously with DZN (70 mg/kg) and Res (20 mg/kg); for a period of 5 weeks. The serum, liver, kidney, and heart levels of the Copper (Cu), zinc (Zn), iron (Fe), selenium (Se), and magnesium (Mg) as main trace elements are measured. ResultsDZN treatment decreased significantly serum, liver, kidney, and heart levels of Cu, Zn, Fe, Se, and Mg in comparison with the control group. Res administration enhanced serum, liver, kidney, and content of heart elements compared to the DZN group. ConclusionsThese results suggested that Res could ameliorate the homeostatic imbalance induced by DZN. Res had a protective effect against DZN-provoking heart, renal, and hepatic toxicity in animal models.

The Role of mTOR in the Doxorubicin-Induced Cardiotoxicity: A Systematic Review.

Doxorubicin (DOX) is a chemotherapy drug known to induce metabolic changes in the heart, leading to potential heart toxicity. These changes impact various cellular functions and pathways such as disrupting the mechanistic target of rapamycin (mTOR) signaling pathway. The study aimed to investigate the effect of DOX on the mTOR pathway through an in vivo systematic review. Databases were searched on September 11, 2023. We finally included 30 in vivo studies that examined the mTOR expression in cardiac tissue samples. The present study has shown that the PI3K/AKT/mTOR, the AMPK/mTOR, the p53/mTOR signaling, the mTOR/TFEB pathway, the p38 MAPK/mTOR, the sestrins/mTOR, and the KLF15/eNOS/mTORC1 signaling pathways play a crucial role in the development of DOX-induced cardiotoxicity. Inhibition or dysregulation of these pathways can lead to increased oxidative stress, apoptosis, and other adverse effects on the heart. Strategies that target and modulate the mTOR pathways, such as the use of mTOR inhibitors like rapamycin, have the potential to enhance the anticancer effects of DOX while also mitigating its cardiotoxic side effects.

Cardiotoxicity Induced by Intratracheal Instillation of Diesel Exhaust Particles in Mice, and the Protective Effects of Carnosol: Suppression of Inflammation and Oxidative and Nitrosative Stress via Modulation of NF-κb/MAPKs Signaling Pathways.

Inhaled particulate air pollution is associated with cardiotoxicity with underlying mechanisms including oxidative stress and inflammation. Carnosol, commonly found in rosemary and sage, is known to possess a broad range of therapeutic properties such as antioxidant, anti-inflammatory and antiapoptotic. However, its cardioprotective effects on diesel exhaust particles (DEPs)-induced toxicity have not been studied yet. Hence, we evaluated the potential ameliorative effects of carnosol on DEPs-induced heart toxicity in mice, and the underlying mechanisms involved. Mice were intratracheally instilled with DEPs (1 mg/kg) or saline, and 1 hour prior to instillation they were given intraperitoneally either carnosol (20 mg/kg) or saline. Twenty-four hours after the DEPs instillation, multiple parameters were evaluated in the heart by enzyme-linked immunosorbent assay, colorimetric assay, Comet assay and Western blot technique. Carnosol has significantly reduced the elevation in the plasma levels of lactate hydrogenase and brain natriuretic peptide induced by DEPs. Likewise, the augmented cardiac levels of proinflammatory cytokines, lipid peroxidation, and total nitric oxide in DEPs-treated groups were significantly normalized with the treatment of carnosol. Moreover, carnosol has markedly reduced the heart mitochondrial dysfunction, as well as DNA damage and apoptosis of mice treated with DEPs. Similarly, carnosol significantly reduced the elevated expressions of phosphorylated nuclear factor-кB (NF-кB) and mitogen-activated protein kinases (MAPKs) in the hearts. Furthermore, the treatment with carnosol has restored the decrease in the expression of sirtuin-1 in the hearts of mice exposed to DEPs. Carnosol significantly attenuated DEP-induced cardiotoxicity in mice by suppressing inflammation, oxidative stress, DNA damage, and apoptosis, at least partly via mechanisms involving sirtuin-1 activation and the inhibition of NF-кB and MAPKs activation.

Targeting Rab7-Rilp Mediated Microlipophagy Alleviates Lipid Toxicity in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DbCM) is characterized by diastolic dysfunction, which progresses into heart failure and aberrant electrophysiology in diabetic patients. Dyslipidemia in type 2 diabetic patients leads to the accumulation of lipid droplets (LDs) in cardiomyocytes and results in lipid toxicity which has been suggested to drive DbCM. It is aimed to explore potential pathways that may boost LDs degradation in DbCM and restore cardiac function. LDs accumulation resulted in an increase in lipid toxicity in DbCM hearts is confirmed. Microlipophagy pathway, rather than traditional macrolipophagy, is activated in DbCM hearts. RNA-Seq data and Rab7-CKO mice implicate that Rab7 is a major modulator of the microlipophagy pathway. Mechanistically, Rab7 is phosphorylated at Tyrosine 183, which allows the recruitment of Rab-interacting lysosome protein (Rilp) to proceed LDs degradation by lysosome. Treating DbCM mice with Rab7 activator ML-098 enhanced Rilp level and rescued the observed cardiac dysfunction. Overall, Rab7-Rilp-mediated microlipophagy may be a promising target in the treatment of lipid toxicity in DbCM is suggested.

Ephedra: An anti-asthamatic medicinal plant

ailments such as cold, cough, asthma, fever and flu. It is distributed in many regions such as Asia, Europe, North Africa, Western North America and South America. It has more than 100 active compounds with effects. It contains flavonoids, alkanes, tannins, sugars and organic phenolic acids. It is used in the treatment of asthma, liver disease, skin disease and other diseases, the most important among the effectiveness of the treatment of the disease is COVID-19. It is considered an ancient group and is appreciated for its abundant fossil record. Ephedra, known as "Ephedra" in China, is a gymnosperm plant. It is a dry straw stalk associated with the lung and bladder meridians. Ephedra is one of the largest genera of the Ephedra family and is found in arid and semi-arid regions of the world. In traditional medicine in many countries, some of these species are frequently used to treat asthma, colds, flu, colds, fever, headaches, nasal congestion and cough. The chemical composition of the ephedra plant has been a focus of interest for decades due to its content of ephedrine alkaloids and its medicinal properties. Other chemical compounds such as phenolics and amino acid derivatives are also of interest and provide evidence-based support for the ethnomedical use of Ephedra. Medicinal plants contain many phytochemical compounds related to various treatments (Naiá et al., 2005; Ghoíbani, 2005). Therefore, this medicinal herb is used in various ephedrine formulations and has many adverse effects on diseases such as liver diseases, angle-closure glaucoma, kidney stones, neurodegenerative diseases and heart toxicity. Indian Ayurveda is a traditional herbal medicine with a long history and strong foundations. Medicinal plants play an important role in the prevention and treatment of human diseases. This plant usually grows on dry rocks and soil because it needs high, dry mountain forests to grow. Many parts of plants such as branches and roots are used in various applications for medicinal purposes. For example, the dry part of the plant is used in vartonic medicine systems such as Ayurveda, Siddha and traditional Chinese medicine to treat many diseases such as asthma, hay fever, pain or inflammation, lung disease, heart disease. Aches, coughs, and colds are considered flu-like symptoms.

In Vitro Antitumor and Antioxidant Capacity as well as Ameliorative Effects of Fermented Kefir on Cyclophosphamide-Induced Toxicity on Cardiac and Hepatic Tissues in Rats.

Fermented prebiotic and probiotic products with kefir are very important to slow down and prevent the growth of tumors and to treat cancer by stimulating the immune response against tumor cells. Cyclophosphamide (CPx) is widely preferred in cancer treatment but its effectiveness in high doses is restricted because of its side effects. The aim of this study was to investigate the protective effects of kefir against CPx-induced heart and liver toxicity. In an experiment, 42 Wistar albino rats were divided into six treatment groups: the control (Group 1), the group receiving 150 mg/kg CPx (Group 2), the groups receiving 5 and 10 mg/kg kefir (Groups 3 and 4) and the groups receiving 5 and 10 mg/kg kefir + CPx (Group 5 and 6). Fermented kefirs obtained on different days by traditional methods were mixed and given by gavage for 12 days, while a single dose of CPx was administered intraperitoneally (i.p.) on the 12th day of the experiment. It was observed that alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine kinase-MB (CK-MB), ischemia modified albumin (IMA) and Troponin I values, which indicate oxidative stress, increased in the CPx-administered group, and this level approached that of the control in the CPx + kefir groups. Likewise, as a result of the kefir, the rats' CPx-induced histopathological symptoms were reduced, and their heart and liver tissue were significantly improved. In conclusion, it was observed that kefir had a cytoprotective effect against CPx-induced oxidative stress, hepatotoxicity and cardiotoxicity, bringing their biochemical parameters closer to those of the control by suppressing oxidative stress and reducing tissue damage.

Mitigation of cisplatin-induced cardiotoxicity by Isorhamnetin: Mechanistic insights into oxidative stress, inflammation, and apoptosis modulation

The flavonoid compound Isorhamnetin (IRMN) is known for its considerable pharmacological properties, which include antioxidant and anti-inflammatory effects, as well as significant protective actions on heart health. However, the potential of IRMN to guard against heart damage caused by cisplatin (CP), a common chemotherapeutic agent, and the specific mechanisms involved, remain unexplored areas. This research was designed to investigate how IRMN counters CP-induced heart toxicity. In our study, mice were orally given IRMN at 50 or 150 mg/kg/day for a week, followed by CP injections (5 mg/kg/day) on the third and sixth days. The animals were euthanized under sodium pentobarbital anesthesia (50 mg/kg, intraperitoneally) on the eighth day to collect blood and heart tissues for further examination. Our findings reveal that IRMN administration significantly reduced the heart damage and the elevation of heart injury markers such as cardiac troponin I, creatine kinase, and lactate dehydrogenase induced by CP. IRMN also effectively lowered oxidative stress markers, including reactive oxygen species and malondialdehyde, while boosting ATP production and antioxidants like superoxide dismutase, catalase, and glutathione. The compound’s capability to diminish the levels of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin-6, alongside modulating apoptosis-regulating proteins (enhancing Bcl-2 while suppressing Bax and Caspase-3 expression), further underscores its cardioprotective effect. Notably, IRMN modulated the p62–Keap1–Nrf2 signaling pathway, suggesting a mechanism through which it exerts its protective effects against CP-induced cardiac injury. These insights underscore the potential of IRMN as an effective adjunct in cancer therapy, offering a strategy to mitigate the cardiotoxic side effects of cisplatin.

Retraction Note: Ameliorating effect of melatonin against nicotine induced lung and heart toxicity in rats.

Retraction Note: Ameliorating effect of melatonin against nicotine induced lung and heart toxicity in rats.

Edaravone and obeticholic acid protect against cisplatin-induced heart toxicity by suppressing oxidative stress and inflammation and modulating Nrf2, TLR4/p38MAPK, and JAK1/STAT3/NF-κB signals

Cardiotoxicity is a significant adverse effect of cisplatin (CIS) that necessitates extensive medical care. The current study examines the cardioprotective effects of edaravone (EDV), obeticholic acid (OCA), and their combinations on CIS-induced cardiac damage. Rats were allocated into five groups: the normal control group, the remaining four groups received CIS (7.5 mg/kg, i.p.) as a single dose on the fifth day and were assigned to CIS, OCA (10 mg/kg/day) + CIS, EDV (20 mg/kg/day) + CIS, and the (EDV + OCA) + CIS group. Compared to the CIS-treated group, co-treating rats with EDV, OCA, or their combinations significantly decreased ALP, AST, LDH, CK-MB, and troponin-I serum levels and alleviated histopathological heart abnormalities. Biochemically, EDV, OCA, and EDV plus OCA administration mitigated cardiac oxidative stress as indicated by a marked decrease in heart MDA content with a rise in cardiac antioxidants SOD and GSH associated with upregulating Nrf2, PPARγ, and SIRT1 expression. Besides, it dampened inflammation by decreasing cardiac levels of TNF-α, IL-1β, and IL-6, mediated by suppressing NF-κB, JAK1/STAT3, and TLR4/p38MAPK signal activation. Notably, rats co-administered with EDV plus OCA showed noticeable protection that exceeded that of EDV and OCA alone. In conclusion, our study provided that EDV, OCA, and their combinations effectively attenuated CIS-induced cardiac intoxication by activating Nrf2, PPARγ, and SIRT1 signals and downregulating NF-κB, JAK1/STAT3, and TLR4/p38MAPK signals.Graphical Outlined diagram summarized the possible protective mechanisms of OCA and/or EDV against cisplatin-induced cardiac injury

The Cardioprotective Effect of Nacetylcysteine on Doxorubicin Induced Cardiotoxicity in Heart Tissue of Rats.

Doxorubicin (DOX) is a chemotherapeutic agent and is widely used in cancer treatment. There are some studies suggesting oxidative stress-induced toxic changes in the liver due to DOX administration. The aim of this study was to reveal the oxidative damage of DOX in liver tissue at molecular level and to evaluate the protective effect of N-acetylcysteine (NAC) against DOX oxidative damage. Twenty four rats weighing 150-200 g were randomly divided into four equal groups; group I : control, group 2: received a single dose of DOX, group 3: received NAC for 28 days and group 4: received a single dose of DOX, followed by NAC for 28 days. At the end of the experiment, heart tissues were taken from all animals. Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), Total Oxidant Capacity (TOC) levels were determined in these samples by spectrophotometric methods. It was determined that TOC level increased, TAC levels decreased in the group given DOX compared to the control group. In addition, TAC levels increased in the DOX+NAC group (p0.05). It was concluded that DOX administration increased oxidative stress and NAC administration could prevent it. NAC caused modulatory effects on oxidative stress and antioxidant redox system in DOX-induced heart toxicity in the rat.

Flaxseed oil fraction reverses cardiac remodeling at a molecular level: improves cardiac function, decreases apoptosis, and suppresses miRNA-29b and miRNA 1 gene expression.

Flaxseed is an ancient commercial oil that historically has been used as a functional food to lower cholesterol levels. However, despite its longstanding treatment, there is currently a lack of scientific evidence to support its role in the management of cardiac remodeling. This study aimed to address this gap in knowledge by examining the molecular mechanism of standardized flaxseed oil in restoring cardiac remodeling in the heart toxicity vivo model. The oil fraction was purified, and the major components were standardized by qualitative and quantitative analysis. In vivo experimental design was conducted using isoproterenol ISO (85mg/kg) twice subcutaneously within 24h between each dose. The rats were treated with flaxseed oil fraction (100mg/kg orally) and the same dose was used for omega 3 supplement as a positive control group. The GC-MS analysis revealed that α-linolenic acid (24.6%), oleic acid (10.5%), glycerol oleate (9.0%) and 2,3-dihydroxypropyl elaidate (7%) are the major components of oil fraction. Physicochemical analysis indicated that the acidity percentage, saponification, peroxide, and iodine values were 0.43, 188.57, 1.22, and 122.34 respectively. As compared with healthy control, ISO group-induced changes in functional cardiac parameters. After 28-day pretreatment with flaxseed oil, the results indicated an improvement in cardiac function, a decrease in apoptosis, and simultaneous prevention of myocardial fibrosis. The plasma levels of BNP, NT-pro-BNP, endothelin-1, Lp-PLA2, and MMP2, and cTnI and cTn were significantly diminished, while a higher plasma level of Topo 2B was observed. Additionally, miRNA - 1 and 29b were significantly downregulated. These findings provide novel insight into the mechanism of flaxseed oil in restoring cardiac remodeling and support its future application as a cardioprotective against heart diseases.

Evaluation of aconitine cardiotoxicity with a heart-on-a-particle prepared by a microfluidic device.

A heart-on-a-particle model based on multicompartmental microgel is proposed to simulate the heart microenvironment and study the cardiotoxicity of drugs. The relevant microgel was fabricated by a biocompatible microfluidic-based approach, where heart function-related HL-1 and HUVEC cells were arranged in separate compartments. Finally, the mechanism of aconitine-induced heart toxicity was elucidated using mass spectrometry and molecular biotechnology.

Anthracycline-related cardiotoxicity in patients with breast cancer harboring mutational signature of homologous recombination deficiency (HRD)

The BRCA proteins play a key role in the homologous recombination (HR) pathway. Beyond BRCA1/2, other genes are involved in the HR repair (HRR). Due to the prominent role in the cellular repair process, pathogenic or likely pathogenic variants (PV/LPVs) in HRR genes may cause inadequate DNA damage repair in cardiomyocytes. This was a multicenter, hospital-based, retrospective cohort study to investigate the heart toxicity from anthracycline-containing regimens (ACRs) in the adjuvant setting of breast cancer (BC) patients carrying germline BRCA PV/LPVs and no-BRCA HRR pathway genes. The left ventricular ejection fraction (LVEF) was assessed using cardiac ultrasound before starting ACR therapy and at subsequent time points according to clinical indications. Five hundred and three BC patients were included in the study. We predefined three groups: (i) BRCA cohort; (ii) no-BRCA cohort; (iii) variant of uncertain significance (VUS)/wild-type (WT) cohort. When baseline (T0) and post-ACR (T1) LVEFs between the three cohorts were compared, pre-treatment LVEF values were not different (BRCA1/2 versus HRR-no-BRCA versus VUS/WT cohort). Notably, during monitoring (T1, median 3.4 months), patients carrying BRCA or HRR no-BRCA germline pathogenic or likely pathogenic variants showed a statistically significant reduction of LVEF compared to baseline (T0). To assess the relevance of HRR on the results, we included the analysis of the subgroup of 20 BC patients carrying PV/LPVs in other genes not involved in HRR, such as mismatch repair genes (MUTYH, PMS2, MSH6). Unlike HRR genes, no significant differences in T0-T1 were found in this subgroup of patients. Our data suggest that deleterious variants in HRR genes, leading to impaired HR, could increase the sensitivity of cardiomyocytes to ACR in early BC patients. In this subgroup of patients, other measurements, such as the global longitudinal strain, and a more in-depth assessment of risk factors may be proposed in the future to optimize cardiovascular risk management and improve long-term survival.

An open source auto-segmentation algorithm for delineating heart and substructures – Development and validation within a multicenter lung cancer cohort

Background and purposeIrradiation of the heart in thoracic cancers raises toxicity concerns. For accurate dose estimation, automated heart and substructure segmentation is potentially useful. In this study, a hybrid automatic segmentation is developed. The accuracy of delineation and dose predictions were evaluated, testing the method's potential within heart toxicity studies. Materials and MethodsThe hybrid segmentation method delineated the heart, four chambers, three large vessels, and the coronary arteries. The method consisted of a nnU-net heart segmentation and partly atlas- and model-based segmentation of the substructures. The nnU-net training and atlas segmentation was based on lung cancer patients and was validated against a national consensus dataset of 12 patients with breast cancer. The accuracy of dose predictions between manual and auto-segmented heart and substructures was evaluated by transferring the dose distribution of 240 previously treated lung cancer patients to the consensus data set. ResultsThe hybrid auto-segmentation method performed well with a heart dice similarity coefficient (DSC) of 0.95, with no statistically significant difference between the automatic and manual delineations. The DSC for the chambers varied from 0.78-0.86 for the automatic segmentation and was comparable with the inter-observer variability. Most importantly, the automatic segmentation was as precise as the clinical experts in predicting the dose distribution to the heart and all substructures. ConclusionThe hybrid segmentation method performed well in delineating the heart and substructures. The prediction of dose by the automatic segmentation was aligned with the manual delineations, enabling measurement of heart and substructure dose in large cohorts. The delineation algorithm will be available for download.

The Efficacy of Grape Seed extract and lycopene as Antioxidants on Experimentally Induced Heart Toxicity in Male Albino Rats

The Efficacy of Grape Seed extract and lycopene as Antioxidants on Experimentally Induced Heart Toxicity in Male Albino Rats

Appraisal of anti-arthritic potential of Coronopus didymus (L.) Sm. aqueous extract and its safety study in Wistar rats.

The current study aimed to find out the anti-arthritic activity and safety study of Coronopus didymus aqueous extract (CDAE) as well as its chemical characterization by HPLC-DAD. Safety study including acute and subacute toxicity studies of the plant aqueous extract was also performed. In complete Freund's adjuvant-induced arthritic model (CFA), 0.15ml CFA was injected in the left hind paw at day 1 in all rats except normal rats. Treatment with CDAE at 200, 400, and 800mg/kg and methotrexate (1mg/kg) was administered at day 8 and continued till 28th day using oral gavage. The CDAE considerably (p < 0.05) reduced the paw swelling and arthritic score, and reinstated the body weight and blood parameters. The CDAE considerably modulated superoxide dismutase, catalase, reduced glutathione, and malondialdehyde level in liver homogenate in contrast to disease control. The CDAE at 400mg/kg considerably reduced IL-6, IL -1β, COX-2, and NF-ĸβ, whereas elevated IL-10, IL-4, and I-kappa β as equated to disease and standard groups. The LD50 of CDAE > 2000mg/kg. In subacute toxicity study, CDAE at 200-800mg/kg did not exhibit clinical signs of toxicity, mortality, hematological, biochemical, and histological alteration in the liver heart, kidney, and lungs in contrast to the normal group. It was concluded that the presence of delphinidine-3-glucoside, diosmetin, 3-feruloyl-4,5-dicaffeoyl quinic acid, and gallic acid in CDAE might be accountable for its anti-arthritic activity and safe use for a long period.

Ameliorative Activity of Vitamin C against Alcohol Induced Cardio-toxicity in Adult Male Wistar Rats

Highlights: 1. Ameliorative effects of vitamin C against alcohol in this research are very interesting to be observed. 2. Vitamin C may have some beneficial effects on heart function by acting as an antioxidant. - Background: Alcohol and it metabolites causes cardiomyopathy, which is one of the main form of alcohol induced heart damage. The aim of the present study was to investigate the protective effect of vitamin C against alcohol-induced heart toxicity and selected indices. Material and Methods: Forty healthy male Wistar rats were used in this experiment, which lasted 21 days. The rats were divided into eight groups, with five rats in each group. Group A received only distilled water, Group B received 6000 mg/kg of alcohol, and Groups C to H received different doses of vitamin C and alcohol in varying combinations. Blood samples were collected and analyzed for levels of sodium, potassium, and chloride ions. The hearts were also analyzed for antioxidant activities and histo-pathological changes. Results: The findings indicated that alcohol administration caused a decrease in blood electrolyte levels compared to the control group, while treatment with vitamin C and co-administration of vitamin C and alcohol improved blood electrolyte levels. The antioxidant enzymes activity of the heart improved in the vitamin C and co-administration groups, as evidenced by increased GSH, SOD, and CAT activity and decreased MDA levels when compared to the alcohol-only group. Conclusion: Therefore, this study suggests that commercial grade vitamin C at doses of 100 mg/kg, 200 mg/kg, and 300 mg/kg can protect the heart against alcohol-induced toxicity. However, further research is necessary to examine the anti-inflammatory effect of commercial grade vitamin C.