scholarly journals Therapeutic Impact of Costus (Saussurea lappa) Against Ehrlich Solid Tumor-Induced Cardiac Toxicity and DNA Damage in Female Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Rehab M. Elgharabawy ◽  
Ibrahim El Tantawy El Sayed ◽  
Nada Abd-Allah Rezk ◽  
Ehab Tousson

Breast cancer remains the most common cause of cancer deaths among women globally. Ehrlich solid tumor (EST) is a transplantable tumor model for simulating breast cancer. This study aims to describe the protective role of costus (Saussurea lappa) root against EST-induced cardiac toxicity. Forty female mice were randomly and equally divided into four groups (G1, control group; G2, costus group; G3, EST group; G4, EST + costus). The results showed that compared to the control, EST induced a significant increase in lactate dehydrogenase, creatine kinase, creatine kinase myoglobin, aspartate aminotransferase, and alkaline phosphatase activities; in potassium, chloride ion, cholesterol, triglyceride, and low density lipoprotein levels; in DNA damage and cardiac injury; and in p53 and vascular endothelial growth factor expression. Conversely, EST induced a significant decrease in sodium ion and high density lipoprotein levels and Ki67 expression compared to the control. Treatment of EST with costus improved cardiac toxicity, lipid profiles, electrolytes, and apoptosis, and protected against EST. This indicates the potential benefits of costus as an adjuvant in the prevention and treatment of cardiac toxicity.

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Márcia Fernanda Correia Jardim Paz ◽  
André Luiz Pinho Sobral ◽  
Jaqueline Nascimento Picada ◽  
Ivana Grivicich ◽  
Antonio Luiz Gomes Júnior ◽  
...  

This study aimed to evaluate DNA damage in patients with breast cancer before treatment (background) and after chemotherapy (QT) and radiotherapy (RT) treatment using the Comet assay in peripheral blood and the micronucleus test in buccal cells. We also evaluated repair of DNA damage after the end of RT, as well as the response of patient’s cells before treatment with an oxidizing agent (H2O2; challenge assay). Fifty women with a mammographic diagnosis negative for cancer (control group) and 100 women with a diagnosis of breast cancer (followed up during the treatment) were involved in this study. The significant DNA damage was observed by increasing in the index and frequency of damage along with the increasing of the frequency of micronuclei in peripheral blood and cells of the buccal mucosa, respectively. Despite the variability of the responses of breast cancer patients, the individuals presented lesions on the DNA, detected by the Comet assay and micronucleus Test, from the diagnosis until the end of the oncological treatment and were more susceptible to oxidative stress. We can conclude that the damages were due to clastogenic and/or aneugenic effects related to the neoplasia itself and that they increased, especially after RT.


2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Xuguang Hu ◽  
Dan Ding ◽  
Jiayi Zhang ◽  
Jianguo Cui

Abstract Radiotherapy is a major therapeutic strategy for breast cancer, while cancer radioresistance remains an obstacle for the successful control of the tumor. Novel radiosensitizing targets are to be developed to overcome radioresistance. Recently, long non-coding RNAs (lncRNAs) were proved to play critical roles in cancer progression. Among all, lncRNA HOTAIR was found to participate in cancer metastasis and chemoresistance. In the present study, we aimed to investigate the radiosensitizing effects of targeting HOTAIR and the underlying mechanism. Our data showed that HOTAIR (HOX antisense intergenic RNA) was up-regulated in breast cancer cells and tissues, and the expression of HOTAIR increased following irradiation. Knockdown of HOTAIR inhibited cell survival and increased cell apoptosis in response to ionizing radiation. Moreover, compared with control group, radiation induced more DNA damage and cell cycle arrest in HOTAIR knockdown cells. Finally, we found that the radiosentizing effects of HOTAIR were related to the up-regulation of miR-218, a ceRNA of HOTAIR. In conclusion, our finding showed that HOTAIR inhibition sensitizes breast cancer cells to ionizing radiation, induced severe DNA damage and activated apoptosis pathways, suggesting a possible role of HOTAIR as a novel target for breast cancer radiosensitization.


1992 ◽  
Vol 10 (1) ◽  
pp. 117-127 ◽  
Author(s):  
J L Speyer ◽  
M D Green ◽  
A Zeleniuch-Jacquotte ◽  
J C Wernz ◽  
M Rey ◽  
...  

PURPOSE To test potential protection by ICRF-187 against cumulative doxorubicin-dose-related cardiac toxicity, we conducted a randomized clinical trial in 150 women with advanced breast cancer. PATIENTS AND METHODS Patients received fluorouracil (5FU) 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 every 21 days intravenously (IV) (control regimen, 74 patients), or the same regimen preceded by ICRF-187 1,000 mg/m2 IV (experimental regimen, 76 patients). RESULTS We previously reported that ICRF-187 in this dose and schedule provides cardiac protection and does not substantially alter the noncardiac toxicity or antitumor efficacy of the control regimen. In this updated analysis of the entire patient cohort, we provide additional support for these findings and demonstrate that patients in the ICRF-187 group received more cycles (median, 11) and higher cumulative doses (median, 500 mg/m2) of doxorubicin than patients in the control group (median, nine cycles, P less than .01; and 441 mg/m2, P less than .05). Twenty-six patients in the ICRF-187 group received doxorubicin doses of at least 700 mg/m2, and among them, 11 patients received 1,000 mg/m2 or more. Only three patients in the control group received doxorubicin doses of 700 mg/m2; the maximum dose administered to one patient in this group was 950 mg/m2. ICRF-187 cardiac protection was demonstrated by difference in incidence of clinical congestive heart failure (CHF; two patients in the ICRF-187 group v 20 in the control group; P less than .0001) and by differences in resting left ventricular ejection fraction (LVEF) determined by multigated radionuclide (MUGA) scan from baselines and that required patient removal from study (five patients in the ICRF-187 group had a decrease in LVEF to less than 0.45 or a decrease from the baseline LVEF of 0.20 or more v 32 in the control group; P less than .000001). Among the 30 patients who had an assessable endomyocardial biopsy at cumulative doxorubicin 450 mg/m2, none of 16 in the ICRF-187 group and six of 14 in the control group had a score of 2 (P less than .05). ICRF-187 cardiac protection was observed in patients with and without prior chest-wall radiation or other risk factors for developing doxorubicin cardiac toxicity. CONCLUSION By protecting against cumulative doxorubicin-induced cardiac toxicity, ICRF-187 permits significantly greater doses of doxorubicin to be administered to patients with greater safety.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Seema Zargar ◽  
Mona Alonazi ◽  
Humaira Rizwana ◽  
Tanveer A. Wani

Background. Thioacetamide (TAA), a class 2B-type carcinogen, is a potent toxicant. Toxicities caused by this compound in various tissues due to oxidative stress, increase of proinflammatory markers, and apoptosis have been reported; however, reports on kidney toxicity are negligible. Resveratrol (RSV), on the other hand, has demonstrated antioxidant and anti-inflammatory effects in different cases. Resveratrol’s protective effects against TAA kidney toxicity were investigated in four rat groups. Methodology. Four groups of rats were studied as follows (n=8): control group, where rats were fed normal diet and water; TAA group, where rats received 0.3% TAA in water for two weeks; RSV group, where rats received 10 mg/kg body weight (bw) of RSV as oral suspension for two weeks; and treated group, where rats orally received 10 mg/kg bw RSV and simultaneously received 0.3% TAA for two weeks. Kidney homogenates from all groups were analyzed for cytokine release (IL-4, TNF-α, and IFN-γ) and oxidative stress (lipid peroxidation, catalase, and 8-OHdG). The serum of rats was analyzed for the quantification of renal function markers (blood urea nitrogen (BUN), creatinine, and creatine kinase). Result. A significant increase in the renal function markers (BUN, 240%; creatinine, 187%; and creatine kinase, 117%), oxidative stress parameters (lipid peroxidation, 192% increase; catalase, 30.5% decrease), cytokines (IL-4, 120%; TNF-α, 129%; and IFN-γ, 133%), and DNA damage was observed in the TAA-treated group. All changes were significantly reversed in the group treated with RSV and TAA (P<0.05) in combination, with no significant difference compared to the control group. Conclusion. We conclude that resveratrol shows protection against TAA toxicity in rat kidney with respect to DNA damage, oxidative stress, renal function and cytokine release.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fatama Akter Chowdhury ◽  
Md Faridul Islam ◽  
Mahnaz Tabassum Prova ◽  
Mahbuba Khatun ◽  
Iffat Sharmin ◽  
...  

Abstract Background The association of circulating lipids with breast cancer is being debated. The objective of this study was to examine the relationship between abnormal plasma lipids and breast cancer risk in Bangladeshi women. Methods This was a case-control study designed using a population of 150 women (50 women in each group). The lipid levels of women with breast cancer were compared to the lipid levels of women with benign breast disease (control group 1) and healthy women (control group 2). Study samples were collected from the Department of Surgery, Bangabandhu Sheikh Mujib Medical University, for a period of 1 year. Ethical measures were in compliance with the current Declaration of Helsinki. Statistical analysis was performed with SPSS version 26. Results All of the comparison groups shared similar sociodemographic, anthropometric and obstetric characteristics. The incidence of dyslipidemia was significantly higher in breast cancer patients (96%) than in healthy women (84%) and patients with benign breast disease (82%) (P < 0.05 for both). The levels of total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol among the breast cancer patient group were significantly higher than those among both benign breast disease patients and healthy women (P < 0.05), except for high-density lipoprotein (HDL) cholesterol. Adjusting for other factors, body mass index (BMI) (kg/m2) (> 23) [OR 53.65; 95% CI: 5.70–504.73; P < 0.001] and total cholesterol (mg/dl) (≥ 200) [OR 16.05; 95% CI: 3.13–82.29; P < 0.001] were independently associated with breast cancer. Conclusions Total cholesterol and BMI are independent predictors of breast cancer risk among Bangladeshi women.


2017 ◽  
Vol 48 (1) ◽  
Author(s):  
Al-Subaihawi & et al.

This study was conducted  to explain the possibility of lyophilization of low – density lipoprotein (LDL)  that is extracted from the egg yolk to be used instead of the egg yolk in  a dilute  semen of Awassi sheep and its  impact on  the rate of deformities of sperm  after stored at 5 ° C for five days. The study  was conducted from September 2015 to February  2016 and in three stages. The first stage started from July until August 2015 in the laboratory of viruses, that is a related Department to the plant protection office. During this stag the (LDL) was extracted  through several sequential steps from fresh egg yolk, and purified and stored in Fastened and steriled vials which are refrigerated until the time of lyophilization. The second stage was conducted  in August  2015 in Al-Kindy company. During  this study the liquid (LDL) was  lyophilized  and kept in steriled and tightly- fostened viols and then was stored in under the  0°C . The  third stage was conducted in the college of Agriculture/ University of Baghdad. In this stage the semen was collected from four of the Awassi rams of the age (2 – 4) years .The semen samples were collected using artificial vagina and the pooled, to remove  the individual differences between the rams. Later on the sample was divided on the experimental treatments evenly 1 ml/ transaction using a dilute Tris with 1:10 dilution ratio. The different concentrations of LDL on the characteristics of semen have also been studied. However; the experiment was conducted from January to February 2016 and during which three concentrations of LDL have been used (3.2 , 4.8 and 6.2%) the transactions T1, T2 , and respectively and the control treatment (20% EY). The improve of the lyophilized LDL has been studied on the different kinds of distortions that effect the sperm at  preservation temperature 5°C, for five consecutive days. Results of the experiment to outweigh LDL transactions in the low proportion of the various distortions that happens to sperm in distortions head swollen to the control group in two days, third, fourth and zero, distortions on other days as well as these transactions excelled in deformation of the tail broken on the fourth day, and in other types of malformations observed failure the presence of significant difference between the control group as in the distortions severed head and tail severed tail twisted as well as the lack of distortions in other types as in distortions tail double moderation bulging and widget, we conclude from the foregoing the possibility of using LDL lyophilized in thinners semen because of its ability in maintaining semen and reduce some types of malformations as well as he did not adversely affect the sperm as it was similar to egg yolk in maintaining sperm if not better.


2016 ◽  
Vol 36 (8) ◽  
pp. 795-801 ◽  
Author(s):  
C Yavas ◽  
G Yavas ◽  
H Toy ◽  
O Ata

Postmenopausal patients with breast cancer have two options for adjuvant endocrine therapy, tamoxifen and aromatase inhibitors (AIs) as well as radiotherapy (RT) and chemotherapy. However, there is limited data regarding the optimal sequencing of RT and tamoxifen/AIs. Thus, we aimed to evaluate the effects of tamoxifen and AIs on radiation-induced cardiotoxicity. Eighty ovariectomized rats were divided into eight groups (G). G1 was defined as a control group; G2, G3, G4, and G5 were RT, tamoxifen, anastrozle, and letrozole groups, respectively; G6, G7, and G8 were RT plus tamoxifen, anastrozle, and letrozole groups, respectively. Drugs were started 1 week before RT and continued until the animals were killed 16 weeks after RT. The heart tissues were then dissected and examined with light microscopy to determine endocardial thickness and cardiac fibrosis. The endocardial thickness scores of both RT alone and the tamoxifen groups as well as the cardiac fibrosis score of RT alone were higher than that the control group ( p < 0.05 for all). There was no difference in the endocardial thickness and cardiac fibrosis scores of the RT-only group and the RT plus hormonotherapy groups ( p > 0.05 for all). Concurrent administration of RT and hormonal therapy with either tamoxifen or AIs did not further amplify radiation-induced cardiac toxicity. This issue warrants further study.


Author(s):  
Rana Hazim Hamoode ◽  
Mohammed Qais Al-ani ◽  
Fareed Arrak Turkey

Objective: Investigating the role of alterations in lipid profile in Iraqi women with breast cancer before and after chemotherapy.Methods: A total number of 100 patients aged 25–47 years were enrolled in this study, including 35 breast cancer treatment patients, 30 treatment patients, and 10 and 25 healthy women benefactor. All samples were collected from August 2016 to February 2017 from Oncology Hospital/Medical city in Baghdad; however, control group samples were collected from outside the hospital. Serum total cholesterol, serum triglyceride, and serum high-density lipoprotein cholesterol (HDL-C) were measured by spectrophotometer using a kit provided by Linear Chemicals.Results: The results show a highly significant increment (p˂0.01) in lipid profile in breast cancer, especially in diagnosis group as compared with other groups.Conclusion: The alteration in cholesterol, triglyceride, HDL-C, and very low-density lipoprotein is highly connected with breast cancer in Iraqi women, progression of disease and treatment effect.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Ehab Tousson ◽  
Rehab Mohmed Elgharabawy ◽  
Thanaa Ahmed Elmasry

The effect of anabolic androgenic steroids on the cardiovascular system is poorly understood. Increased production of free radicals is coupled to the pathophysiology of many alterations within the circulatory system. The only function of the enzyme family NADPH oxidases (NOXs) is the generation of reactive oxygen species (ROS). Therefore, this study investigated the beneficial role of grape seed proanthocyanidin extract (GSPE) in ameliorating cardiac toxicity induced by the anabolic steroid Boldenone in male rats through NOX inhibition and reduction in the expression of NOX2 and NOX4. This study was conducted on forty male rats which are divided into four groups (normal control, positive control or GSPE, Boldenone, and posttreatment Boldenone with GSPE). A significant increase in relative body weight, relative heart weight, and hemodynamic parameters, as well as serum concentrations of lactate dehydrogenase, creatine kinase, creatine kinase-muscle brain, myoglobin, cholesterol, low-density lipoprotein cholesterol, risk factor 1/2, K+, and Cl−, in treated rats with Boldenone when compared with control. We also noted a significant increase in the levels of cardiac malondialdehyde, H2O2generation in heart tissues, mRNA expression of NOX2 and NOX4, and immunoreactivity to proliferating cell nuclear antigen (PCNA). Posttreated rats with Boldenone and GSPE ameliorated cardiac toxicity via inhibition of NOX and a reduction in alteration of the expression of NOX2, NOX4, and PCNA induced by Boldenone. These novel insights into the antioxidative activity of GSPE should serve as a basis for the development of improved chemopreventive or therapeutic strategies for cardiac toxicity.


2018 ◽  
Vol 11 (1) ◽  
pp. 70-83
Author(s):  
G Al-Rubaie ◽  
H Ajeel ◽  
S Khalaf

The experiment was conducted in the field of animal production of the research ruminants- Office of Research- Ministry of Agriculture in the region of Akrokov 25 km northwest of Baghdad for the period from 16/3/2016 to 4/6/2016, and the objective of the experiment was the effect of addition of different levels of fibrolytic enzymes. The concentrate diet on some characteristics biochemical blood lactating Ewes Awassi, In the first experiment, 26 pregnant sheep were used In the late stage and before birth and at the age of 3-5 years, With a weight of 67 kg, The first experiment lasted 42 days preceded by 10 days introductory period The ewes were divided into four groups, each with 6 ewes, of which 15 were born, Treatment control 3 ewes, first treatment 5 ewes, second treatment 4 ewes, third treatment 3 ewes, The trial period was divided into three successive periods from birth every 14 days, The first period of 0-14 days and the second period of 15-28 days and the third period of 29 to 42 days of the milk cycle began, Control group without enzyme and treatment of the first, second and third enzyme concentration 1,3,5 kg/t respectively. The preliminary period is 10 days ahead, The results showed that: The addition of fibrolytic enzymes to the cencenterate diet of the fodder resulted in Significant increase (P<0.01) was observed at the general rate of concentration of urea, The concentration of urea was significantly increased only in T3, while cholesterol was significantly higher in all treatments compared to the control treatment. And significantly increased triglycerides in T2 compared to all other treatments. Very high-density lipoprotein was increased in T1 treatment with control treatment C, as well as significant increase (P≤0.05) high-density lipoprotein in treatment T1 compared to treatment control C and the recording of high-density lipoprotein (HDL) significantly higher in T2 compared to all treatments triglyceride, and very high-density lipoprotein, (P<0.05) for high density lipoprotein (LDL) and low-density lipoprotein. LDL was significantly increased in T3 compared to T1. The serum AST (T3) was significantly increased in T3 compared to T2, T1 in the serum of lactating ewes.


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