Antitumor effects of atorvastatin in the chemoprevention of rat mammary carcinogenesis

Biologia ◽  
2011 ◽  
Vol 66 (4) ◽  
Author(s):  
Peter Kubatka ◽  
Katarína Žihlavniková ◽  
Peter Solár ◽  
Karol Kajo ◽  
Vanda Valentová ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Latency Period ◽  
Mammary Carcinogenesis ◽  
Epidemiological Studies ◽  
Suppressive Effect ◽  
Female Rats ◽  
Control Group ◽  
Antitumor Effects ◽  
Atorvastatin Treatment ◽  
Reductase Inhibitors

AbstractEpidemiological studies indicate that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, play a role in inhibition of several human neoplasia including breast cancer. In this study, chemopreventive effects of atorvastatin in N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. Atorvastatin was administered in the diet at two concentrations: 10 mg/kg (ATOR 10) and 100 mg/kg (ATOR 100). Atorvastatin treatment began 8 days prior to carcinogen administration and subsequently continued for 15 weeks till the end of the experiment. Atorvastatin at a higher dose suppressed tumor frequency by 80.5% (P = 0.0008) and tumor incidence by 49.5% (P = 0.015), and extended latency period by 14 days (P = 0.076) when compared to the control group. Atorvastatin at a lower dose did not significantly alter tumor parameters in comparison with the control group. In the specimens of mammary tumors, atorvastatin (in the ATOR 100 group) significantly decreased mRNA expression of Bcl-2 gene but non-significantly increased Bax mRNA expression compared to control group. Atorvastatin administration did not alter serum concentration of triacylglycerols, total cholesterol, and LDL cholesterol in comparison with controls. This study is the first report on tumor suppressive effect of atorvastatin in rat mammary carcinogenesis.

scholarly journals Effects of Tocotrienol and Lovastatin Combination on Osteoblast and Osteoclast Activity in Estrogen-Deficient Osteoporosis

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Saif Abdul-Majeed ◽  
Norazlina Mohamed ◽  
Ima-Nirwana Soelaiman
Keyword(s):  
Bone Formation ◽  
Combined Treatment ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Hmgcoa Reductase ◽  
Reductase Inhibitors ◽  
Group 4 ◽  
Group 3 ◽  
Group 2

Statins are HMGCoA reductase inhibitors and had been demonstrated to stimulate bone formation in rodents after high oral doses. Observational studies on patients treated with oral statins were varied. Delta-tocotrienol had been found to stimulate the cleavage of HMGCoA reductase and inhibit its activity. Tocotrienols were found to have both catabolic and anabolic effects on bone in different animal models of osteoporosis. The current study aimed to ascertain the effects of delta–tocotrienol and lovastatin combination on biochemical and static bone histomorphometric parameters in a postmenopausal rat model at clinically tolerable doses. 48 Sprague Dawley female rats were randomly divided into 6 groups: (1) baseline control group; (2) sham-operated control group; (3) ovariectomised control group; (4) ovariectomised and 11 mg/kg lovastatin; (5) ovariectomised and 60 mg/kg delta-tocotrienol; (6) ovariectomised and 60 mg/kg delta-tocotrienol + 11 mg/kg lovastatin. These treatments were given daily via oral gavage for 8 weeks. Delta-tocotrienol plus lovastatin treatment significantly increased bone formation and reduced bone resorption compared to the other groups. Therefore, the combined treatment may have synergistic or additive effects and have the potential to be used as an antiosteoporotic agent in patients who are at risk of both osteoporosis and hypercholesterolemia, especially in postmenopausal women.

scholarly journals Sex and salt intake dependent renin-angiotensin plasticity in the liver of the rat

2019 ◽  
Vol 53 (3) ◽  
pp. 178-186
Author(s):  
Paulina Pidikova ◽  
Pavel Svitok ◽  
Iveta Herichova
Keyword(s):  
Mrna Expression ◽  
Salt Intake ◽  
Renin Angiotensin System ◽  
Significant Negative Correlation ◽  
Epidemiological Studies ◽  
Male Rats ◽  
Control Group ◽  
Salt Diet ◽  
Renin Angiotensin ◽  
Endothelial Growth Factor

AbstractObjective. Epidemiological studies confirm that hypertensive patients respond differently to renin-angiotensin system (RAS) inhibition depending on their gender. The aim of present work is to focus on sex-dependent differences in RAS regulation under conditions of increased salt intake.Method. To investigate RAS, we measured the expression of angiotensinogen (Agt) mRNA, angiotensin receptor type 1 (AT1) mRNA and mitochondria assembly receptor (MasR) in the liver of rats under control conditions and after feeding with a salt diet (2% NaCl). In parallel, vascular endothelial growth factor A (VEGF-A) mRNA was analyzed.Results. Regression analysis revealed sex-dependent differences in the correlation between mRNA expression of AT1 and that of Agt, MasR and VEGF-A in both groups. There was a significant negative correlation between AT1 and Agt mRNA expression in the male control group, but this correlation disappeared in males exposed to a salt diet. In females, AT1 and Agt expression correlated only in the group exposed to the salt diet. In control males, there was a borderline trend to correlation between AT1 and MasR mRNA expression. The correlation between AT1 and VEGF-A mRNA expression was significant only in the control females, however, after exposure to a salt diet, this correlation diminished.Conclusions. We hypothesize that RAS components expression is compensated differently in males and females. The observed loss of compensatory relationships in RAS between AT1 and Agt and AT1 and MasR in male rats under a salt diet can contribute to the differences observed in human with hypertension associated with an unhealthy diet.

Advantages of intraperitoneal chemotherapy in treatment of ovarian cancer peritoneal carcinomatosis

2014 ◽  
Vol 63 (2) ◽  
pp. 28-34
Author(s):  
Yekaterina Aleksandrovna Vyshinskaya ◽  
Vladimir Grigoryevich Bespalov ◽  
Irina Nikolayevna Vasilyeva ◽  
Aleksandr Leonidovich Semenov ◽  
Aleksandr Nikolayevich Stukov ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Antitumor Activity ◽  
Peritoneal Carcinomatosis ◽  
Survival Time ◽  
Mitomycin C ◽  
Intraperitoneal Chemotherapy ◽  
Alkylating Agents ◽  
Female Rats ◽  
Control Group ◽  
Antitumor Effects

The purpose of the study is to compare antitumor activity of different drugs at their Intraperitoneal (i. p.) and intravenous (i.v.) administration in rats with ovarian cancer peritoneal carcinomatosis. The study was carried out in 124 Wistar female rats with ovarian cancer which was inoculated i. p. After ovarian cancer inoculation rats were randomized in 12 groups, 10 rats in each group. There were six groups where saline (2 ml, i.p. control group) or the drugs (dioxadet 1.5 mg/kg, cisplatin 4mg/kg, mitomycin C 1.5 mg/kg, melphalan 2 mg/kg, paclitaxel 5 mg/kg) were administered i. p. In other six groups saline (2 ml, i. v. control group) and the named above drugs at the same doses were administered i. v. Antitumor effects of the treatment were estimated by increase in survival time (IST) comparing median survival time of rats in different groups. IST for i.p. administration of dioxadet, cisplatin, melphalan, mitomycin C and paclitaxel were 79 % (p < 0.001), 88 % (p < 0.001), 114 % (p < 0.001), 35 % (p < 0.002) and 45 % (p < 0.001) correspondingly compared to i.p. control group while for i.v. administration of these drugs IST were 5 % (p = 0.796), 14 % (p = 0.315), 19 % (p = 0.631), 152 % (p < 0.001) and 81 % (p = 0.023) correspondingly compared to i. v. control group. Thus, i. p. chemotherapy with alkylating agents dioxadet, cisplatin and melphalan is much more effective then their i. v. administration, while antitumor effects of i. p. and i. v. administration of paclitaxel were similar and only mitomycin C is more active at i. v. administration.

The effect of bromocriptine on mammary-gland ultrastructure of hyperprolactinemic rats

1984 ◽  
Vol 42 ◽  
pp. 204-205
Author(s):  
I.C. Murray
Keyword(s):  
Mammary Gland ◽  
Dopamine Agonist ◽  
Alveolar Epithelium ◽  
Mammary Glands ◽  
Female Rats ◽  
Control Group ◽  
Cell Hyperplasia ◽  
Once Daily ◽  
Long Evans

In women, hyperprolactinemia is often due to a prolactin (PRL)-secreting adenoma or PRL cell hyperplasia. RRL excess stimulates the mammary glands and causes proliferation of the alveolar epithelium. Bromocriptine, a dopamine agonist, inhibits PRL secretion and is given to women to treat nonpuerperal galactorrhea. Old female rats have been reported to have PRL cell hyperplasia or adenoma leading to PRL hypersecretion and breast stimulation. Herein, we describe the effect of bromocriptine and consequently the reduction in serum PRL levels on the ultrastructure of rat mammary glands.Female Long-Evans rats, 23 months of age, were divided into control and bromocriptine-treated groups. The control animals were injected subcutaneously once daily with a 10% ethanol vehicle and were later divided into a normoprolactinemic control group with serum PRL levels under 30 ng/ml and a hyperprolactinemic control group with serum PRL levels above 30 ng/ml.

MODULATION OF TRIGLYCERIDES IN FEMALE RATTUS RATTUS WITH STEROID CONTRACEPTIVE ALGESTONE ACETOPHENIDE (DHPA)

2019 ◽  
Vol 25 (1) ◽  
Author(s):  
ASHOK KUMAR ◽  
ALPANA PARMAR ◽  
ANAND KUMAR BAJPEYEE
Keyword(s):  
Mixed Type ◽  
Rattus Rattus ◽  
Young Female ◽  
Female Rats ◽  
Control Group ◽  
Black Rat ◽  
Long Acting ◽  
Steroid Contraceptive

Young female Black rat (Rattus rattus), were administered monthly long acting steroid contraceptive to induce hypertriglyceridemia. It was observed that by 3 weeks of the second injection of estrogen containing mixed type of contraceptive, female rats developed consistent and frank hyperglyceridemia . TG in the treated rats was 195.8 ± 7.44 mg /100 ml as compared to 91.5 ± 6.27 mg/100ml in plasma of the control group.

Apoptotic Effects of Melittin on 4T1 Breast Cancer Cell Line is associated with Up Regulation of Mfn1 and Drp1 mRNA Expression

2020 ◽  
Vol 20 (7) ◽  
pp. 790-799 ◽  
Author(s):  
Farnaz D. Moghaddam ◽  
Pejman Mortazavi ◽  
Somayeh Hamedi ◽  
Mohammad Nabiuni ◽  
Nasim H. Roodbari
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Hemolytic Activity ◽  
Breast Cancer Cells ◽  
Flow Cytometric Analysis ◽  
Control Group ◽  
Flow Cytometric ◽  
4T1 Cells ◽  
4T1 Breast Cancer ◽  
Apoptotic Effects

Background and Purpose: Melittin, as the main ingredient of honeybee venom, that has shown anticancer properties. The present study aimed at investigating the cytotoxic impacts of melittin on 4T1 breast cancer cells. Methods: Hemolytic activity of different concentrations (0.125, 0.25, 0.5, 1, 2, 4, 8μg/ml) of melittin was assayed and then cytotoxicity of selected concentrations of melittin (2, 4, 8, 16, 32, and 64μg/ml), 2 and 4μg/ml of cisplatin and 0.513, 0.295 and 0.123μg/ml of doxorubicin was evaluated on 4T1 cells using MTT assay. We used Morphological evaluation and flow cytometric analysis was used. Real time PCR was also used to determine mRNA expression of Mfn1 and Drp1 genes. Results: All compounds showed anti-proliferative effects on the tumor cell line with different potencies. Melittin had higher cytotoxicity against 4T1 breast cancer cells (IC50= 32μg/ml-72h) and higher hemolytic activity (HD50= 1μg/ml), as compared to cisplatin and doxorubicin. Mellitin at 16 and 32μg/ml showed apoptotic effects on 4T1 cells according to the flow cytometric analysis. The Real time PCR analysis of Drp1 and Mfn1 expression in cells treated with 16μg/ml of melittin revealed an up-regulation in Drp1 and Mfn1 genes mRNA expression in comparison with control group. Treatment with 32μg/ml of melittin was also associated with a rise in mRNA expression of Drp1 and Mfn1 as compared to the control group. Conclusion: The results of this study showed that melittin has anticancer effects on 4T1 cell lines in a dose and time dependent manner and can be a good candidate for further research on breast cancer treatment.

Effect of Fetal and Neonatal Hypothyroidism on Glucose Tolerance in Middle-Aged Female Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Sajad Jeddi ◽  
Saeedeh Khalifi ◽  
Mahboubeh Ghanbari ◽  
Asghar Ghasemi
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Female Offspring ◽  
Female Rats ◽  
Control Group ◽  
Female Rat ◽  
Middle Aged ◽  
Intravenous Glucose ◽  
Neonatal Hypothyroidism ◽  
Glucose Levels

Background and objective: The effects of hypothyroidism during pregnancy and lactation on carbohydrate metabolism have been mostly studied in male animals. The aim of this study is therefore to investigate effect of fetal and neonatal hypothyroidism (FH and NH) on the glucose tolerance in middle-aged female rat offspring. Methods: Pregnant female rats were divided into three groups: Rats in the control group consumed tap water, while those in the FH and NH groups consumed 250 mg/L of 6-propyl-2-thiouracil (PTU) in their drinking water during gestation or lactation periods, respectively. After weaning, the female offspring were separated and divided into 3 groups (n=8/group): Control, FH, and NH. Body weight was recorded monthly and intravenous glucose tolerance test (IVGTT) was performed at month 12. Results: Compared to controls, female rats in the FH group had significantly higher plasma glucose levels than controls throughout the IVGTT except at min 60. Values at min 5 of the FH and control group were 196.1±1.9 and 155.3±5.9 mg/dL, respectively (P<0.05). In the NH group, plasma glucose levels were significantly higher only at min 5 (185.7±14.1 vs. 155.3±5.9 mg/dL, P<0.05). Conclusion: Hypothyroidism during fetal or neonatal periods caused glucose intolerance in middle-aged female offspring rats.

scholarly journals Urinary bisphenol A in women with polycystic ovary syndrome – a possible suppressive effect on steroidogenesis?

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Zora Lazúrová ◽  
Jana Figurová ◽  
Beáta Hubková ◽  
Jana Mašlanková ◽  
Ivica Lazúrová
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Bisphenol A ◽  
Steroid Hormones ◽  
Polycystic Ovary ◽  
Suppressive Effect ◽  
Human Reproduction ◽  
Control Group ◽  
Ovary Syndrome ◽  
Ovarian Steroidogenesis ◽  
The Relationship

Abstract Objectives There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. Methods Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. Results PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. Conclusions PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.

Comparison of streptozotocin-induced diabetes at different moments of the life of female rats for translational studies

2021 ◽  
pp. 002367722110018
Author(s):  
Yuri K Sinzato ◽  
Eduardo Klöppel ◽  
Carolina A Miranda ◽  
Verônyca G Paula ◽  
Larissa F Alves ◽  
...  
Keyword(s):  
Adult Life ◽  
Tolerance Test ◽  
Full Term ◽  
Female Rats ◽  
Lower Percentage ◽  
Control Group ◽  
Oral Glucose ◽  
Postnatal Life ◽  
Sprague Dawley ◽  
Term Pregnancy

Animal models are widely used for studying diabetes in translational research. However, methods for induction of diabetes are conflicting with regards to their efficacy, reproducibility and cost. A comparison of outcomes between the diabetic models is still unknown, especially full-term pregnancy.To understand the comparison, we analyzed the streptozotocin (STZ)-induced diabetes at three life-different moments during the neonatal period in Sprague–Dawley female rats: at the first (D1), second (D2) and fifth (D5) day of postnatal life. At adulthood (90 days; D90), the animals were submitted to an oral glucose tolerance test (OGTT) for diabetic status confirmation. The diabetic and control rats were mated and sacrificed at full-term pregnancy for different analyses. Group D1 presented a higher mortality percentage after STZ administration than groups D2 and D5. All diabetic groups presented higher blood glucose levels as compared to those of the control group, while group D5 had higher levels of glycemia compared with other groups during OGTT. The diabetic groups showed impaired reproductive outcomes compared with the control group. Group D1 had lower percentages of mated rats and D5 showed a lower percentage of a full-term pregnancy. Besides that, these two groups also showed the highest percentages of inadequate fetal weight. In summary, although all groups fulfill the diagnosis criteria for diabetes in adult life, in our investigation diabetes induced on D5 presents lower costs and higher efficacy and reproducibility for studies involving diabetes-complicated pregnancy.

scholarly journals Gold Nanoparticles Affect Pericyte Biology and Capillary Tube Formation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 738
Author(s):  
Sasikarn Looprasertkul ◽  
Amornpun Sereemaspun ◽  
Nakarin Kitkumthorn ◽  
Kanidta Sooklert ◽  
Tewarit Sarachana ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Endothelial Cell ◽  
Mrna Expression ◽  
Capillary Tube ◽  
Quantitative Polymerase Chain Reaction ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
Control Group ◽  
Capillary Tubes ◽  
Cell Functions

Gold nanoparticles (AuNPs) are used for diagnostic and therapeutic purposes, especially antiangiogenesis, which are accomplished via inhibition of endothelial cell proliferation, migration, and tube formation. However, no research has been performed on the effects of AuNPs in pericytes, which play vital roles in endothelial cell functions and capillary tube formation during physiological and pathological processes. Therefore, the effects of AuNPs on the morphology and functions of pericytes need to be elucidated. This study treated human placental pericytes in monoculture with 20 nm AuNPs at a concentration of 30 ppm. Ki-67 and platelet-derived growth factor receptor-β (PDGFR-β) mRNA expression was measured using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell migration was assessed by Transwell migration assay. The fine structures of pericytes were observed by transmission electron microscopy. In addition, 30 ppm AuNP-treated pericytes and intact human umbilical vein endothelial cells were cocultured on Matrigel to form three-dimensional (3D) capillary tubes. The results demonstrated that AuNPs significantly inhibited proliferation, reduced PDGFR-β mRNA expression, and decreased migration in pericytes. Ultrastructural analysis of pericytes revealed AuNPs in late endosomes, autolysosomes, and mitochondria. Remarkably, many mitochondria were swollen or damaged. Additionally, capillary tube formation was reduced. We found that numerous pericytes on 3D capillary tubes were round and did not extend their processes along the tubes, which resulted in more incomplete tube formation in the treatment group compared with the control group. In summary, AuNPs can affect pericyte proliferation, PDGFR-β mRNA expression, migration, morphology, and capillary tube formation. The findings highlight the possible application of AuNPs in pericyte-targeted therapy for antiangiogenesis.

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