Lipoic acid stimulates bone formation in ovariectomized rats in a dose-dependent manner

2016 ◽  
Vol 94 (9) ◽  
pp. 947-954 ◽  
Author(s):  
Radoslaw Piotr Radzki ◽  
Marek Bienko ◽  
Dariusz Wolski ◽  
Alicja Lis ◽  
Agnieszka Radzka
Keyword(s):  
Body Mass ◽  
Lipoic Acid ◽  
Experimental Treatment ◽  
Physiological Saline ◽  
Ovariectomized Rats ◽  
Sham Operation ◽  
Dependent Manner ◽  
Skeletal Density ◽  
Female Wistar Rats ◽  
Dose Dependent

This study was undertaken to determine the osteotropic effect of different doses of lipoic acid (LA) on the mineralization of bone tissue in female Wistar rats with experimental osteopenia induced by bilateral ovariectomy. Fifty-six rats were randomly selected and submitted to either a sham operation (n = 8) or an ovariectomy (n = 48). The ovariectomized rats were randomly placed into two control groups, treated subcutaneously with either physiological saline or 17β-estradiol in the dose of 4 μg/kg body mass per day, and four experimental groups that received LA subcutaneously in the doses of 12.5, 25, 50, and 100 mg/kg body mass per day (n = 8 in each group). After 28 days of experimental treatment, the rats were sacrificed, and body mass, total skeletal density, and body composition were recorded. Blood serum and isolated femora were stored for further analysis. Our results revealed that the osteoprotective effect of LA was dose-dependent and was observed in rats treated with 50 and 100 mg/kg of LA. Moreover, the LA applied to the ovariectomized rats in the dose of 50 mg/kg not only stopped the bone resorption, but stimulated its formation.

scholarly journals Camelina Oil Supplementation Improves Bone Parameters in Ovariectomized Rats

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1343
Author(s):  
Iwona Puzio ◽  
Dorota Graboś ◽  
Marek Bieńko ◽  
Radosław P. Radzki ◽  
Aneta Nowakiewicz ◽  
...  
Keyword(s):  
Serum Level ◽  
Recovery Period ◽  
Physiological Saline ◽  
Ovariectomized Rats ◽  
Control Group ◽  
Sham Operation ◽  
Type I ◽  
Camelina Oil ◽  
Bone Parameters ◽  
Ovx Rats

The aim of the present study was to determine the effect of administration of Camelina sativa oil (CO) as a source of polyunsaturated fatty acids (PUFA) on bone parameters in ovariectomized rats (OVX). Overall, 40 10-week-old healthy female Wistar rats were divided into 4 groups with 10 animals in each. Rats in the control group (SHO) were subjected to a sham operation, whereas experimental rats (OVX) were ovariectomized. After a 7-day recovery period, the SHO the rats received orally 1 mL of physiological saline for the next 6 weeks. The OVX rats received orally 1 mL of physiological saline (OVX-PhS), 5 g/kg BW (OVX-CO5), or 9 g/kg BW (OVX-CO9) of camelina oil. The use of camelina oil had a significant effect on body weight, lean mass, and fat mass. The camelina oil administration suppressed the decrease in the values of some densitometric, tomographic, and mechanical parameters of femur caused by estrogen deficiency. The CO treatment increased significantly the serum level of osteocalcin and decreased the serum level of C-terminal telopeptide of type I collagen in the OVX rats. In conclusion, camelina oil exerts a positive osteotropic effect by inhibiting ovariectomy-induced adverse changes in bones. Camelina oil supplementation can be used as an efficient method for improving bone health in a disturbed state. However, further research must be carried out on other animal species supplemented with the oil.

scholarly journals α-Lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio in human bone marrow stromal cells

2005 ◽  
Vol 185 (3) ◽  
pp. 401-413 ◽  
Author(s):  
Jung-Min Koh ◽  
Young-Sun Lee ◽  
Chang-Hyun Byun ◽  
Eun-Ju Chang ◽  
Hyunsoo Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lipoic Acid ◽  
Nuclear Factor Κb ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Mouse Bone Marrow ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Receptor Activator ◽  
Dose Dependent

Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. Although α-lipoic acid (α-LA) has been shown to act as a thiol antioxidant, its effect on bone cells has not been determined. Using proteomic analysis, we identified six differentially expressed proteins in the conditioned media of α-LA-treated human bone marrow stromal cell line (HS-5). One of these proteins, receptor activator of nuclear factor κB ligand (RANKL), was significantly up-regulated, as confirmed by immunoblotting with anti-RANKL antibody. ELISA showed that α-LA stimulated RANKL production in cellular extracts (membranous RANKL) about 5-fold and in conditioned medium (soluble RANKL) about 23-fold, but had no effect on osteoprotegerin (OPG) secretion. Despite increasing the RANKL/OPG ratio, α-LA showed a dose-dependent suppression of osteoclastogenesis, both in a coculture system of mouse bone marrow cells and osteoblasts and in a mouse bone marrow cell culture system, and reduced bone resorption in a dose-dependent manner. In addition, α-LA-induced soluble RANKL was not inhibited by matrix metalloprotease inhibitors, indicating that soluble RANKL is produced by α-LA without any posttranslational processing. In contrast, α-LA had no significant effect on the proliferation and differentiation of HS-5 cells. These results suggest that α-LA suppresses osteoclastogenesis by directly inhibiting RANKL–RANK mediated signals, not by mediating cellular RANKL production. In addition, our findings indicate that α-LA-induced soluble RANKL is not produced by shedding of membranous RANKL.

Premorbid body mass and mortality in patients with hepatocellular cancer: A systematic review and meta-analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 477-477 ◽  
Author(s):  
Arjun Gupta ◽  
Avash Das ◽  
Nivedita Arora ◽  
Kaustav Majumder ◽  
Preet Paul Singh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Morbid Obesity ◽  
Body Mass ◽  
Meta Analysis ◽  
Hepatocellular Cancer ◽  
Dependent Manner ◽  
Increased Risk ◽  
Reported Data ◽  
Dose Dependent ◽  
Related Mortality

477 Background: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid body mass index (BMI) and HCC mortality. Methods: Through a systematic search of major databases and conference proceedings, up to March 2016, we identified observational studies reporting the association between premorbid BMI, and HCC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CI), comparing obese (BMI > 30 kg/m2) and overweight (BMI 25-29.9 kg/m2) categories with reference category using random effects model; heterogeneity was measured using the inconsistency index (I2). Results: 9 studies were included in which 6,052 HCC deaths occurred in 1,599,453 cancer-free individuals at cohort inception. 5 studies reported data as obese vs. overweight vs. normal BMI, and 4 reported data as obese + overweight combined (BMI > 25 kg/m2). On meta-analysis, pre-morbid obesity was associated with higher HCC-related mortality, as compared to individuals with normal BMI (obese: aHR, 1.96; 95% CI, 1.46-2.46, I2= 37%; overweight: aHR, 1.08; 95% CI, 0.97-1.21, I2= 0%), in dose-dependent manner. This effect was stronger in males [3 studies, aHR, 2.50; 95% CI, 2.02-3.09] vs. females [2 studies, aHR, 1.45; 95% CI, 1.08-1.97]. This effect was seen primarily in Western populations [4 studies, aHR, 2.10; 95% CI, 1.77-2.48], but not in Asian population [1 study, aHR, 1.10; 95% CI, 0.63-1.92]. Conclusions: In this meta-analysis, there was a dose-dependent increase in HCC-related mortality with pre-morbid obesity, particularly in men, and in Western populations. Strategies targeting obesity-induced metabolic abnormalities may provide novel pathways for HCC therapy.

scholarly journals The effects of prolonged oral administration of the disinfectant calcium hypochlorite in Nigerian commercial cockerels

2013 ◽  
Vol 84 (1) ◽  
Author(s):  
Temitayo O. Iji ◽  
Ademola A. Oyagbemi ◽  
Odunayo I. Azeez
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Oral Administration ◽  
Prolonged Exposure ◽  
Density Lipoprotein ◽  
Physiological Saline ◽  
Antioxidant Defense System ◽  
Dependent Manner ◽  
Calcium Hypochlorite ◽  
Dose Dependent

This study was designed to investigate the effects of prolonged oral administration of calcium hypochlorite in the drinking water of commercial cockerels. It was carried out in order to ascertain probable toxicity associated with prolonged exposure to calcium hypochlorite. Thirty-two healthy birds were used; they were grouped into four groups of eight. Group 1, which served as the control, received 10 mL/kg body weight of physiological saline. Groups 2, 3 and 4 received 0.0375 g, 0.375 g and 0.75 g of calcium hypochlorite per 10 litres of drinking water for six weeks respectively. Six weeks after the administration of calcium hypochlorite, blood was collected from the jugular vein to assess liver function, lipid profiles and for markers of oxidative stress. The results revealed a significant (p < 0.05) increase in alanine aminotransferase activity in a dose-dependent manner when compared with the control. Also, there was a significant (p < 0.05) increase in aspartate aminotransferase and alkaline phosphatase activity. Similarly, there was a significant (p < 0.05) increase in total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein levels compared with the control. There was a significant increase in malondialdehyde and hydrogen peroxide generation with a concomitant significant (p < 0.05) decrease in serum glutathione level in a dose-dependent manner when compared with the control. In this study, calcium hypochloriteinduced hepatic damage via oxidative stress and decrease in antioxidant defense system was found. Therefore, prolonged exposure of chickens to calcium hypochlorite is potentially harmful.

Efficacy of Alpha-Lipoic Acid in Iron-Induced Oxidative Stress.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3599-3599
Author(s):  
Ashutosh Lal ◽  
Jung H. Suh ◽  
Bruce N. Ames
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
Lipoic Acid ◽  
Iron Content ◽  
Redox State ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Dependent Manner ◽  
Intracellular Iron ◽  
Dose Dependent

Abstract Antioxidant supplementation could reduce organ damage and premature death in patients with iron overload. We evaluated the improvement in iron-induced oxidative stress with α-Lipoic acid (LA), a multifunctional thiol antioxidant and inducer of phase II enzymes, and compared it with benzylhydroxylamine (BH), a reducing agent that protects against free radicals. Human fibroblasts (IMR-90) were grown in regular cell culture medium or with ferric ammonium citrate (FAC). The intracellular iron content was measured by inductively-coupled plasma spectrometry (ICP). Either LA or BH was added on day 2, and cells grown to confluence. Oxidative stress was assessed by dichlorodihydrofluorescein diacetate fluorescence (DCF-fl). GSH:GSSG was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total intracellular iron content (mean±SEM, ng per 5x10^6 cells) increased from 66.95±6.51 in control cells to 262.26±4.69 after exposure to 25 μM FAC, and 556.26±21.15 after exposure to 125 μM FAC. The increase in iron-content of the IMR-90 fibroblasts caused significant rise in oxidant appearance at the highest concentration, as evidenced by 27.8±2.6% increase in steady-state DCF-fl compared with control cells (p &lt;.001). Addition of increasing concentrations of LA attenuated iron-mediated rise in DCF-fl in dose dependent manner. LA at concentrations above 25 μM completely abolished the iron-dependent rise in DCF-fl (91.9±2.3% for FAC+LA, p &lt;.001). BH treated cells also exhibited a dose-dependent decrease in DCF-fl, but a much higher concentration (&gt;200 μM) was needed for complete attenuation of iron-induced rise in DCF-fl (108.3±3.4%, p &lt;.001). These results suggest that LA is more effective than BH in ameliorating iron-mediated increase in oxidative stress. To further understand the basis for the efficacy of LA, intracellular GSH and GSSG were measured. Results show that LA improved the total GSH levels and its redox state in a dose dependent manner. LA and BH attenuated iron-mediated oxidant production, with LA exhibiting greater efficacy. This effect may be due to potent ability of LA to improve intracellular GSH levels and redox state. Our results suggest LA may be useful in reducing complications from iron overload.

scholarly journals IL-6 Up-Regulates the Expression of Rat LH Receptors during Granulosa Cell Differentiation

Endocrinology ◽  
2014 ◽  
Vol 155 (4) ◽  
pp. 1436-1444 ◽  
Author(s):  
Fumiharu Imai ◽  
Hiroshi Kishi ◽  
Kohshiro Nakao ◽  
Toshio Nishimura ◽  
Takashi Minegishi
Keyword(s):  
Mrna Expression ◽  
Granulosa Cells ◽  
Ovarian Function ◽  
Luciferase Assay ◽  
Dependent Manner ◽  
Signal Transducer ◽  
Female Wistar Rats ◽  
Translational Start ◽  
Transcription 3 ◽  
Dose Dependent

IL-6 is produced in granulosa cells under normal physiological conditions, including during ovulation. However, the roles of IL-6 in ovarian function, including regulation of LH receptor (LHR) expression in granulosa cells, have not been explored in detail. The aim of this study was to identify the mechanism underlying the effect of IL-6 on LHR expression in the granulosa cells of female Wistar rats. Our results indicated that IL-6 clearly enhanced the FSH-induced LHR mRNA expression in a dose-dependent manner and did not stimulate cAMP accumulation by itself. The membrane protein level of LHR, assessed by a binding assay, was increased by FSH and was further enhanced by association with IL-6. Results of the luciferase assay, using promoter constructs of LHR 281 bp upstream of the translational start site, revealed that IL-6 increased the promoter activity induced by FSH, but this effect was not observed with treatment by IL-6 alone. This ability of IL-6 to enhance FSH-induced LHR mRNA expression was blocked by the Janus tyrosine kinase (JAK) pathway inhibitor, but not by the ERK1/2 inhibitor. Thus, we speculated that this IL-6 activity might be mediated by the JAK/signal transducer and activator of transcription pathway. In addition, IL-6 augmented FSH-induced IL-6 receptor α mRNA expression and FSH elevated IL-6 production in granulosa cells, which indicates that IL-6 may positively regulate paracrine and autocrine actions in granulosa cells. These results suggest that IL-6 up-regulates FSH-induced LHR production by increasing mRNA transcription, and JAK/signal transducer and activator of transcription 3 signaling is required for up-regulation by IL-6 in granulosa cells.

scholarly journals Human chorionic gonadotropin regulates gastric emptying in ovariectomized rats

2012 ◽  
Vol 216 (3) ◽  
pp. 307-314 ◽  
Author(s):  
Kok-Min Seow ◽  
Jyun-Lin Lee ◽  
Ming-Luen Doong ◽  
Seng-Wong Huang ◽  
Jiann-Loung Hwang ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Gastrointestinal Transit ◽  
First Trimester ◽  
Dose Effect ◽  
Ovariectomized Rats ◽  
Dependent Manner ◽  
Ovx Rats ◽  
Dose Dependent

Prolongation of gastrointestinal transit resulting in nausea and vomiting in pregnancy (NVP) is the most common phenomenon during the first trimester of pregnancy. Increased human chorionic gonadotropin (hCG) concentration during the first trimester is the most likely cause of NVP. The aim of this study was to investigate the effect of hCG on gastrointestinal transit and plasma concentrations of cholecystokinin (CCK) in ovariectomized (Ovx) rats. I.p. injection of hCG was used to evaluate the dose effect of hCG on gastrointestinal transit in Ovx rats. The CCK antagonist lorglumide was used to clarify the role of CCK in regulating gastrointestinal transit. Gastrointestinal transit was assessed 15 min after intragastric gavage of a mixture of 10% charcoal and Na251CrO4(0.5 μCi/ml). After i.p. administration of hCG, gastric emptying was inhibited in Ovx rats, but intestinal transit was not affected. Plasma CCK concentrations were increased in a dose-dependent manner after hCG treatment, and gastric emptying showed a significant negative correlation with CCK concentrations (P=0.01,r2=−0.5104). Peripheral administration (i.p.) of lorglumide, a selective CCK1receptor antagonist, attenuated the hCG-induced inhibition of gastric emptying in Ovx rats, whereas central administration via the i.c.v. route did not. hCG treatment of Ovx rats inhibits gastric emptying in a dose-dependent manner via a peripheral mechanism of CCK hypersecretion and activation of CCK1receptors.

scholarly journals Methanolic Extract of Ceplukan Leaf (Physalis minimaL.) Attenuates Ventricular Fibrosis through Inhibition of TNF-αin Ovariectomized Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Bayu Lestari ◽  
Nur Permatasari ◽  
Mohammad Saifur Rohman
Keyword(s):  
Heart Failure ◽  
Treatment Group ◽  
Wistar Rats ◽  
Methanolic Extract ◽  
Ovariectomized Rats ◽  
Dependent Manner ◽  
Estrogen Level ◽  
Menopausal Women ◽  
Ventricular Fibrosis ◽  
Dose Dependent

The increase of heart failure prevalence on menopausal women was correlated with the decrease of estrogen level. The aim of this study is to investigate the effects of ceplukan leaf (Physalis minimaL.), which contains phytoestrogen physalin and withanolides, on ventricular TNF-αlevel and fibrosis in ovariectomized rats. Wistar rats were divided into six groups (control (—); OVX 5: 5-week ovariectomy (OVX); OVX 9: 9-week ovariectomy; treatments I, II, and III: 9-weeks OVX + 4-week ceplukan leaf’s methanolic extract doses 500, 1500, and 2500 mg/kgBW, resp.). TNF-αlevels were measured with ELISA. Fibrosis was counted as blue colored tissues percentage using Masson’s Trichrome staining. This study showed that prolonged hypoestrogen increases ventricular fibrosis (p<0.05). Ceplukan leaf treatment also resulted in a decrease of ventricular fibrosis and TNF-αlevel in dose dependent manner compared to without treatment group (p<0.05). Furthermore, the TNF-αlevel was normalized in 2500 mg/kgBWPhysalis minimaL. (p<0.05) treatment. The reduction of fibrosis positively correlated with TNF-αlevel (p<0.05,r=0.873). Methanolic extract of ceplukan leaf decreases ventricular fibrosis through the inhibition of ventricular TNF-αlevel in ovariectomized rats.

scholarly journals Spirulina platensis ameliorates arsenic-mediated uterine damage and ovarian steroidogenic disorder

FACETS ◽  
2018 ◽  
Vol 3 (1) ◽  
pp. 736-753 ◽  
Author(s):  
Shamima Khatun ◽  
Moulima Maity ◽  
Hasina Perveen ◽  
Moumita Dash ◽  
Sandip Chattopadhyay
Keyword(s):  
Body Mass ◽  
Spirulina Platensis ◽  
Oral Delivery ◽  
Sodium Arsenite ◽  
Experimental Treatment ◽  
Antioxidant Defense System ◽  
Control Group ◽  
Pathological State ◽  
Significant Amelioration ◽  
Female Wistar Rats

Novel, non-invasive, painless oral therapeutic agents are needed to replace the painful conventional treatment of arsenic-associated health hazards with metal chelators. Our aim was to examine the effect of spirulina ( Spirulina platensis ( Geitler, 1925 )) on arsenic-mediated uterine toxicity. Female Wistar rats were divided equally into four experimental treatment groups: control group, sodium arsenite group (1.0 mg/100 g body mass), spirulina placebo group (20 mg/100 g body mass), and sodium arsenite + spirulina group. In contrast with the control group, spectrophotometric and electrozymographic evaluation revealed that rats that ingested arsenic for 8 d showed significant diminution of the activities of superoxide dismutase, catalase, and peroxidase ( p < 0.001). Mutagenic uterine DNA breakage and tissue damage were prominent following arsenic consumption by the rats. Oral delivery of spirulina resulted in a significant amelioration of arsenic-induced adverse oxidative stress and genotoxic state of rats. A significant low-signaling ( p < 0.001) of gonadotropins and estradiol was also noted in the arsenic-treated rats, which was terminated by spirulina; this arsenic-primed adverse effect was significant ( p < 0.05, p < 0.01). The spirulina treatment mechanism could be associated with augmentation of the antioxidant defense system that protects the arsenic-mediated pathological state of the uterus.

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