Anti-osteopenic effect of alpha-ketoglutarate sodium salt in ovariectomized rats

The purpose of the study was to determine the effect of alpha-ketoglutarate sodium salt (AKG) treatment on the mineralization of the tibia in female rats during the development of osteopenia (Experiment-1) and in the condition of established osteopenia (Experiment-2). Thirty-two female rats were ovariectomized (OVX) to induce osteopenia and osteoporosis and another 32 female rats were sham-operated (SHO) and then randomly divided between the two experiments. In Experiment-1, the treatment with AKG started after a 7-day period of convalescence, whereas in Experiment-2 the rats were subjected to a 60-day period of osteopenia fixation, after which the actual experimental protocol commenced. AKG was administered in the experimental solution for drinking at a concentration of 1.0 mol/l and a placebo (PLC) was used as a control solution. After 60 days of experimental treatment the rats in both experiements were sacrificed, the body weight recorded, and blood serum and isolated tibia were stored for further analysis. The bones were analyzed using tomography and densitometry, and for estimation of mechanical properties the 3-point bending test was used. Serum concentrations of osteocalcin and collagen type I crosslinked C-telopeptide were measured. The anabolic effects of AKG on bone during osteopenia development in Experiment-1 not only stopped the degradation of bone tissue, but also stimulated its mineralization. The usage of AKG in animals with established osteopenia (Experiment-2) was not able to prevent bone atrophy, but markedly reduced its intensity. The stimulation of tibia mineralization after AKG treatment has been also argued in healthy SHO animals. The results obtained prove the effectiveness of AKG usage in the prophylaxis and therapy of osteopenia and osteoporosis, induced by bilateral gonadectomy. Additionally, the results clearly prove that treatment with AKG improves the mineralization of bone tissue in healthy animals

Effect of dietary alpha-ketoglutarate on blood lipid profile during hypercholesterolaemia in rats

Objective. The aim of the study was to determine the effect of -ketoglutarate on the blood lipid profile using a rat animal model with experimentally induced hypercholesterolaemia. Material and methods. The female and male (30/30) Wistar rats had ad libitum access to a diet containing cholesterol (1 %) and lard (10 %) throughout the entire experimental period (120 days). On day 60 of the study, both the females and the males were divided into three groups, the first receiving a mixture of drinking water adjusted to pH 4.6 using HCl (control), the other two (experimental groups) receiving a solution containing 0.01 M and 0.1 M -ketoglutarate (AKG) (pH adjusted to 4.6). Blood samples were taken on days 0, 30, 60 and 120. Results. The concentrations of total cholesterol, triglycerides, HDL and LDL, respectively, in the blood serum were estimated spectrophotometrically. During the entire experimental period the total cholesterol, triglycerides and LDL levels of the control rats increased, whereas that of HDL decreased. The serum concentrations of total cholesterol, LDL and triglycerides in both the experimental groups receiving AKG decreased (days 60 to 120) (p0.05), while the HDL concentration tended to increase. The body gain in all groups receiving AKG was significantly lower than in the control group. Conclusions. These observations clearly prove that oral treatment with AKG can decrease the risk of hypercholesterolaemia developing and can lower the body weight. The relative concentrations of the plasma LDL and HDL changed to a more favourable ratio promoting good health

The effect of dietary administration of 2-oxoglutaric acid on the cartilage and bone of growing rats

2-Oxoglutaric acid (2-Ox), a precursor to hydroxyproline - the most abundant amino acid in bone collagen, exerts protective effects on bone development during different stages of organism development; however, little is known about the action of 2-Ox on cartilage. The aim of the present study was to elucidate the influence of dietary 2-Ox supplementation on the growth plate, articular cartilage and bone of growing rats. A total of twelve male Sprague-Dawley rats were used in the study. Half of the rats received 2-oxoglutarate at a dose of 0.75 g/kg body weight per d in their drinking-water. Body and organ weights were measured. Histomorphometric analyses of the cartilage and bone tissue of the femora and tibiae were conducted, as well as bone densitometry and peripheral quantitative computed tomography (pQCT). Rats receiving 2-Ox had an increased body mass (P<0.001) and absolute liver weight (P=0.031). Femoral length (P=0.045) and bone mineral density (P=0.014), overall thickness of growth plate (femur P=0.036 and tibia P=0.026) and the thickness of femoral articular cartilage (P<0.001) were also increased. 2-Ox administration had no effect on the mechanical properties or on any of the measured pQCT parameters for both bones analysed. There were also no significant differences in histomorphometric parameters of tibial articular cartilage and autofluorescence of femoral and tibial growth plate cartilage. Dietary supplementation with 2-Ox to growing rats exerts its effects mainly on cartilage tissue, having only a slight influence on bone. The effect of 2-Ox administration was selective, depending on the particular bone and type of cartilage analysed

Lipoic acid dose-dependently stimulates bone formation in ovariectomized rats

The 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 either with physiological saline or 17β-estradiol in the dose of 4 Οg/kg b.w./day, respectively, and into four experimental groups which received LA subcutaneously in the doses of 12.5, 25, 50 and 100 mg/kg b.w/day (n=8 in each group). After 28 days of experimental treatment, the rats were sacrificed. There-after, body weight, total skeletal density and body composition were recorded. Blood serum and isolated femora were stored for further analysis. Our results revealed that osteoprotective effect of LA is dose-dependent and was observed in females 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.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Osteotropic Effect of Parenteral Obesity in Programmed Male Rats Fed a Calorically Differentiated Diet during Growth and Development

The experiment was undertaken to assess whether the continuation or change of the parents&rsquo; diet affects the previously programmed bone metabolism of the male offspring during its growth and development. A total of 16 male and 32 female Wistar rats were divided into groups and fed a standard (diet S) or high-energy (diet F). After the induction of obesity, the rats from groups S and F, as the parent generation, were used to obtain male offspring, which were kept with their mothers until the weaning day (21 days of age). In our earlier study, we documented the programming effects of the diet used in parents on the skeletal system of offspring measured on the weaning day. Weaned male offspring constitute one control group&mdash;parents and offspring fed the S diet. There were three experimental groups, where: parents received diet S and offspring were fed with the F diet; parents were treated with the diet F, while offspring received the S diet; and parents and offspring were fed with the diet F. The analyses were performed at 49 and 90 days of life. After sacrifice, cleaned-off soft tissue femora were assessed using peripheral quantitative computed tomography (pQCT), dual X-ray absorptiometry (DXA), and a three-point bending test. We observed that changing and continuation of nutrition, applied previously in parents, significantly influenced the metabolism of the bone tissue in male offspring, and the osteotropic effects differed, depending on the character of the nutrition modification and age. Additionally, an important conclusion of our study, regarding the previous, is that nutrition modification, affecting the metabolism of bone tissue, also depends on the sex

When Incorporated into Fruit Sorbet Matrix, Are the Fructans in Natural Raw Materials More Beneficial for Bone Health than Commercial Formulation Added Alone?

We assessed the extent to which fructans from various sources and added in various forms (raw materials in diet alone or incorporated into a strawberry matrix) differ in their effectiveness towards selected parameters related to bone health under calcium hypoalimentation in growing female Wistar rats. The aim of this study was to evaluate the levels of selected parameters involved in calcium metabolism, in response to a 12-week restriction of Ca intake: serum ions (Ca, Mg, P); the activity of alkaline phosphatase&mdash;using a BS 120 analyzer; the markers of bone turnover (osteocalcin, CTX; using a Rat-MidTMOsteocalcinEIA Kit and RatLapsTMEIA, respectively); and the bone mineral content (BMC) and density (BMD), using a Norland Excell Plus Densitometer. Among the examined markers, the CTX concentration increased dramatically under calcium hypoalimentation. The presence of Jerusalem artichoke (independently of the form of addition) and yacon root powder (with strawberry sorbet matrix) in the rats&rsquo; diet led to a significantly lower CTX concentration than was observed in the low-calcium control group. The type of fructan influenced the bone mass content. When fructan was added to the low-calcium diet as an ingredient of sorbet, it exerted more pronounced effects on the biochemical parameters of bone metabolism than when added alone, in the growing-female-rat model

Can 2-oxoglutarate prevent changes in bone evoked by omeprazole?

Objective: Proton-pump inhibitors, such as omeprazole, are widely used in the prevention and treatment of gastroesophageal diseases. However, an association between proton-pump inhibitors and the increased risk of bone fractures has been observed, especially in patients treated for extended periods. Conversely, 2-oxoglutarate, a precursor of hydroxyproline, the most abundant amino acid in bone collagen, counteracts the bone loss. The aim of the present study was to elucidate the influence of omeprazole on bone and investigate whether dietary 2-oxoglutarate supplementation could prevent the effects of omeprazole. Methods: Eighteen male Sprague-Dawley rats were used. Rats received omeprazole in the diet and 2-oxoglutarate in the drinking water. Body and organ weights and serum concentrations of cholecystokinin and gastrin were measured. The femurs, tibias, and calvarias were collected. Histomorphometric analysis of bone and cartilage tissues was conducted. Bone densitometric and peripheral quantitative computed tomographic analyses of the femur and tibia were performed. Results: Omeprazole decreased the femur and tibia weights, the mechanical properties of the femur, the volumetric bone density and content, the trabecular and cortical bone mineral content, the total, trabecular, and cortical bone areas, the mean cortical thickness, and the periosteal circumference of the femur. Omeprazole had a minor effect on the examined bone morphology and exerted negligible effects on the cartilage. 2-Oxoglutarate lowered the gastrin concentration. Conclusions: Omeprazole treatment exerts its effects mostly on bone mineralization and cancellous bone, adversely affecting bone properties. This adverse effect of omeprazole was not markedly abolished by 2-oxoglutaric acid, which acted as an anti-hypergastrinemic agent. (C) 2013 Elsevier Inc. All rights reserved

Programming Effect of the Parental Obesity on the Skeletal System of Offspring at Weaning Day

Our study aimed to verify the hypothesis of the existence of a programming effect of parental obesity on the growth, development and mineralization of the skeletal system in female and male rat offspring on the day of weaning. The study began with the induction of obesity in female and male rats of the parental generation, using a high-energy diet (group F). Females and males of the control group received the standard diet (group S). After 90 days of dietary-induced obesity, the diet in group F was changed into the standard. Rats from groups F and S were mated to obtain offspring which stayed with their mothers until 21 days of age. Tibia was tested using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT) and mechanical strength using the three-point bending test. Biochemical analysis of blood serum bone metabolism markers was performed. DXA analysis showed higher tibia bone mineral content (BMC) and area. pQCT measurements of cortical and trabecular tissue documented the increase of the volumetric bone mineral density and BMC of both bone compartments in offspring from the F group, while µCT of the trabecular tissue showed an increase in trabecular thickness and a decrease of its separation. Parental obesity, hence, exerts a programming influence on the development of the skeletal system of the offspring on the day of the weaning, which was reflected in the intensification of mineralization and increased bone strength

Programming Effect of the Parental Obesity on the Skeletal System of Offspring at Weaning Day

Our study aimed to verify the hypothesis of the existence of a programming effect of parental obesity on the growth, development and mineralization of the skeletal system in female and male rat offspring on the day of weaning. The study began with the induction of obesity in female and male rats of the parental generation, using a high-energy diet (group F). Females and males of the control group received the standard diet (group S). After 90 days of dietary-induced obesity, the diet in group F was changed into the standard. Rats from groups F and S were mated to obtain offspring which stayed with their mothers until 21 days of age. Tibia was tested using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT) and mechanical strength using the three-point bending test. Biochemical analysis of blood serum bone metabolism markers was performed. DXA analysis showed higher tibia bone mineral content (BMC) and area. pQCT measurements of cortical and trabecular tissue documented the increase of the volumetric bone mineral density and BMC of both bone compartments in offspring from the F group, while µCT of the trabecular tissue showed an increase in trabecular thickness and a decrease of its separation. Parental obesity, hence, exerts a programming influence on the development of the skeletal system of the offspring on the day of the weaning, which was reflected in the intensification of mineralization and increased bone strength