scholarly journals Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause

2021 ◽  
Vol 15 ◽  
Author(s):  
Stephanie V. Koebele ◽  
Ryoko Hiroi ◽  
Zachary M. T. Plumley ◽  
Ryan Melikian ◽  
Alesia V. Prakapenka ◽  
...  
Keyword(s):  
Hormone Therapy ◽  
Rat Model ◽  
Ovarian Follicle ◽  
Clinical Findings ◽  
Negative Effects ◽  
Primary Indication ◽  
Endocrine Status ◽  
Conjugated Equine Estrogens ◽  
Physiological Profiles ◽  
Hormonal Milieu

A variety of U.S. Food and Drug Administration-approved hormone therapy options are currently used to successfully alleviate unwanted symptoms associated with the changing endogenous hormonal milieu that occurs in midlife with menopause. Depending on the primary indication for treatment, different hormone therapy formulations are utilized, including estrogen-only, progestogen-only, or combined estrogen plus progestogen options. There is little known about how these formulations, or their unique pharmacodynamics, impact neurobiological processes. Seemingly disparate pre-clinical and clinical findings regarding the cognitive effects of hormone therapies, such as the negative effects associated with conjugated equine estrogens and medroxyprogesterone acetate vs. naturally circulating 17β-estradiol (E2) and progesterone, signal a critical need to further investigate the neuro-cognitive impact of hormone therapy formulations. Here, utilizing a rat model of transitional menopause, we administered either E2, progesterone, levonorgestrel, or combinations of E2 with progesterone or with levonorgestrel daily to follicle-depleted, middle-aged rats. A battery of assessments, including spatial memory, anxiety-like behaviors, and depressive-like behaviors, as well as endocrine status and ovarian follicle complement, were evaluated. Results indicate divergent outcomes for memory, anxiety, and depression, as well as unique physiological profiles, that were dependent upon the hormone regimen administered. Overall, the combination hormone treatments had the most consistently favorable profile for the domains evaluated in rats that had undergone experimentally induced transitional menopause and remained ovary-intact. The collective results underscore the importance of investigating variations in hormone therapy formulation as well as the menopause background upon which these formulations are delivered.

Negative effects of alcohol intake and estrogen deficiency combination on osseointegration in a rat model

2010 ◽  
pp. 110220121911010
Author(s):  
Leonardo Marchini ◽  
Camila de Deco ◽  
Adriana Marchini ◽  
Mary Anne Barbara ◽  
Luana Vasconcellos ◽  
...  
Keyword(s):  
Rat Model ◽  
Alcohol Intake ◽  
Estrogen Deficiency ◽  
Negative Effects

scholarly journals Octanoic acid a major component of widely consumed medium-chain triglyceride ketogenic diet is detrimental to bone

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shreshta Jain ◽  
Reena Rai ◽  
Divya Singh ◽  
Divya Vohora
Keyword(s):  
Bone Loss ◽  
Ketogenic Diet ◽  
Octanoic Acid ◽  
Bone Microarchitecture ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
Clinical Findings ◽  
Micro Computed Tomography ◽  
Negative Effects ◽  
Treatment Groups

AbstractOctanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.

The Effects of Hyperthermic Intraperitoneal Chemoperfusion on Colonic Anastomosis: An Experimental Study in a Rat Model

2017 ◽  
Vol 103 (3) ◽  
pp. 307-313 ◽  
Author(s):  
Afag Aghayeva ◽  
Cigdem Benlice ◽  
Ismail Ahmet Bilgin ◽  
Pinar Atukeren ◽  
Gulen Dogusoy ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Rat Model ◽  
Colonic Anastomosis ◽  
Colorectal Anastomosis ◽  
Sigmoid Resection ◽  
Albino Rats ◽  
Bursting Pressure ◽  
Negative Effects ◽  
Significant Difference ◽  
Group 2

Introduction Cytoreductive surgery (CRS) with subsequent hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising modality to treat and prevent peritoneal metastases. However, this treatment is associated with signficant morbidity and mortality. Whether or not CRS with HIPEC interferes with anastomotic healing has also been debated. This study was designed to investigate the effects of mitomycin C, cisplatin, oxaliplatin, and doxorubicin used in HIPEC treatment on colonic anastomosis healing in a rat model. Methods Sixty Wistar albino rats were employed in the study. Sigmoid resection and end-to-end colorectal anastomosis was performed in all rats. Group 1 rats underwent the surgical procedure alone, while group 2 rats were given hyperthermic intraperitoneal lavage with heated saline following surgery. Groups 3, 4, 5, and 6 had surgery with concomitant HIPEC treatment with mitomycin C, cisplatin, oxaliplatin, and doxorubicin, respectively. Anastomotic bursting pressures and hydroxyproline levels were evaluated. Results Regarding the hydroxyproline levels, groups 1 and 2 showed significantly higher values than other groups (p<0.001). However, there was no significant difference between the HIPEC treatment groups (groups 3, 4, 5, and 6) (p>0.05). When groups were compared regarding bursting pressure values, no significant differences were observed (p = 0.81). Conclusions This study demonstrated that the HIPEC procedure with mitomycin C, cisplatin, oxaliplatin and doxorubicin had negative effects on hydroxyproline levels, but had no detrimental effect on anastomotic bursting pressure in a rat model.

scholarly journals Comparative Analysis of the Uterine and Mammary Gland Effects of Drospirenone and Medroxyprogesterone Acetate

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 3952-3959 ◽  
Author(s):  
Christiane Otto ◽  
Iris Fuchs ◽  
Helga Altmann ◽  
Mario Klewer ◽  
Alexander Walter ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Hormone Therapy ◽  
Women's Health ◽  
Medroxyprogesterone Acetate ◽  
Uterine Activity ◽  
Women's Health Initiative ◽  
Health Initiative ◽  
Conjugated Equine Estrogens ◽  
Equine Estrogens ◽  
The Women’S Health Initiative

The role of progestins in combined hormone therapy is the inhibition of uterine epithelial cell proliferation. The Women’s Health Initiative study provided evidence for an increased risk of breast cancer in women treated with conjugated equine estrogens plus the synthetic progestin medroxyprogesterone acetate (MPA), compared with conjugated equine estrogens-only treatment. These findings continue to be discussed, and it remains to be clarified whether the results obtained for MPA in the Women’s Health Initiative study are directly applicable to other progestins used in hormone therapy. In this study we compared in a mouse model the effects of the synthetic progestins, MPA, and drospirenone in two major target organs: the uterus and mammary gland. As quantitative measures of progestin activity, we analyzed maintenance of pregnancy, ductal side branching in the mammary gland, and proliferation of mammary and uterine epithelial cells as well as target gene induction in both organs. The outcome of this study is that not all synthetic progestins exhibit the same effects. MPA demonstrated uterine activity and mitogenic activity in the mammary gland at the same doses. In contrast, drospirenone behaved similarly to the natural hormone, progesterone, and exhibited uterine activity at doses lower than those leading to considerable proliferative effects in the mammary gland. We hypothesize that the safety of combined hormone therapy in postmenopausal women may be associated with a dissociation between the uterine and mammary gland activities of the progestin component.

scholarly journals The Combination of Atorvastatin With Silymarin Enhances Hypolipidemic, Antioxidant and Anti-Inflammatory Effects in a Rat Model of Metabolic Syndrome

2021 ◽  
pp. 33-43
Author(s):  
I MARKOVÁ ◽  
H MALÍNSKÁ ◽  
M HÜTTL ◽  
D MIKLÁNKOVÁ ◽  
O OLIYARNYK ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Rat Model ◽  
Hdl Cholesterol ◽  
Standard Diet ◽  
Hypolipidemic Effect ◽  
Negative Effects ◽  
Cardioprotective Effects ◽  
Anti Inflammatory ◽  
New Onset

Hypolipidemic and cardioprotective effects of statins can be associated with the development of myopathies and new-onset type 2 diabetes. These adverse effects may be related to increased oxidative stress. The plant extract silymarin (SM) is known for its antioxidant and anti-inflammatory actions. We tested the hypothesis that the combination of atorvastatin (ATV) with SM could improve therapy efficacy and eliminate some negative effects of statin on hypertriglyceridemia-induced metabolic disorders. Hereditary hypertriglyceridemic rats were fed a standard diet for four weeks without supplementation; supplemented with ATV (5 mg/kg b. wt./day) or a combination of ATV with 1 % micronized SM (ATV+SM). ATV treatment elevated plasma levels of HDL-cholesterol (p<0.01), glucose and insulin and decreased triglycerides (p<0.001). The combination of ATV+SM led to a significant reduction in insulin, an improvement of glucose tolerance, and the hypolipidemic effect was enhanced compared to ATV alone. Furthermore, ATV supplementation increased skeletal muscle triglycerides but its combination with SM decreased triglycerides accumulation in the muscle (p<0.05) and the liver (p<0.01). In the liver, ATV+SM treatment increased the activities of antioxidant enzymes, glutathione and reduced lipid peroxidation (p<0.001). The combined administration of ATV with SM potentiated the hypolipidemic effect, reduced ectopic lipid accumulation, improved glucose metabolism, and increased antioxidant and anti-inflammatory actions. Our results show that SM increased the effectiveness of statin therapy in a hypertriglyceridemic rat model of metabolic syndrome.

scholarly journals Short-term perioperative parecoxib is not detrimental to shaft fracture healing in a rat model

2019 ◽  
Vol 8 (10) ◽  
pp. 472-480 ◽  
Author(s):  
Geir A. Hjorthaug ◽  
Endre Søreide ◽  
Lars Nordsletten ◽  
Jan E. Madsen ◽  
Finn P. Reinholt ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Rat Model ◽  
Experimental Studies ◽  
Bending Moment ◽  
Shaft Fracture ◽  
Control Group ◽  
Negative Effects ◽  
Short Term ◽  
Term Administration ◽  
Negative Effect

Objectives Experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) may have negative effects on fracture healing. This study aimed to assess the effect of immediate and delayed short-term administration of clinically relevant parecoxib doses and timing on fracture healing using an established animal fracture model. Methods A standardized closed tibia shaft fracture was induced and stabilized by reamed intramedullary nailing in 66 Wistar rats. A ‘parecoxib immediate’ (Pi) group received parecoxib (3.2 mg/kg bodyweight twice per day) on days 0, 1, and 2. A ‘parecoxib delayed’ (Pd) group received the same dose of parecoxib on days 3, 4, and 5. A control group received saline only. Fracture healing was evaluated by biomechanical tests, histomorphometry, and dual-energy x-ray absorptiometry (DXA) at four weeks. Results For ultimate bending moment, the median ratio between fractured and non-fractured tibia was 0.61 (interquartile range (IQR) 0.45 to 0.82) in the Pi group, 0.44 (IQR 0.42 to 0.52) in the Pd group, and 0.50 (IQR 0.41 to 0.75) in the control group (n = 44; p = 0.068). There were no differences between the groups for stiffness, energy, deflection, callus diameter, DXA measurements (n = 64), histomorphometrically osteoid/bone ratio, or callus area (n = 20). Conclusion This study demonstrates no negative effect of immediate or delayed short-term administration of parecoxib on diaphyseal fracture healing in rats. Cite this article: G. A. Hjorthaug, E. Søreide, L. Nordsletten, J. E. Madsen, F. P. Reinholt, S. Niratisairak, S. Dimmen. Short-term perioperative parecoxib is not detrimental to shaft fracture healing in a rat model. Bone Joint Res 2019;8:472–480. DOI: 10.1302/2046-3758.810.BJR-2018-0341.R1.

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