Vitamin E does not prevent bone loss and induced anxiety in rats with ligature-induced periodontitis.
The purpose of this study was to investigate the effect of vitamin E on alveolar bone loss (ABL) and anxiety in rats with ligature-induced experimental periodontitis (EP).
Wistar rats were subjected to ligature-induced EP and treated with vitamin E (500mg/kg, orally) for 9 days. Then anxiety was tested using the elevated plus-maze (EPM) test. All of the animals were euthanised by cervical dislocation on day 11. ABL was analysed morphometrically and histopathologically. Lipid peroxidation quantification, activity of the enzyme superoxide dismutase and immunohistochemistry to tumour necrosis factor-alpha (TNF-α) and inducible isoform of nitric oxide synthases (iNOS) were also tested.
EP induced a marked inflammatory process and intense ABL. Treatment with vitamin E decreased inflammatory reaction, prevented malondialdehyde formation and reduced the immunoreactivity to iNOS, but did not decrease ABL. Vitamin E had an anxiogenic effect on rats with or without EP.
Vitamin E may have potential to reduce oxidative damage and inflammatory response in EP but does not prevent ABL. Attention should be given to indiscriminate use of vitamin E due to the risk of causing anxiety in patients.
Carvalho Rde S, de Souza CM, Neves JC, Holanda-Pinto SA…
Arch. Oral Biol. Jan 2013
Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol.
Vitamin E homologues, specifically tocotrienols, have been shown to have favorable effects on bone. They possess properties that are indicative of anti-resorptive activity, suggesting the potential for vitamin E in preventing bone loss. To investigate the anti-resorptive activity of the various vitamin E homologues, we cultured human osteoclasts from blood-derived CD14+ cells on collagen, dentin, and calcium phosphate substrates, with some samples supplemented with vitamin E homologues in their cell culture medium. These were compared to the clinically used bisphosphonate, pamidronate. Compounds were either added at the start of culture to study effects on osteoclast formation, or at the start of osteoclastic resorption to determine their effects on activity. The alpha- and gamma-tocotrienol isomers inhibited osteoclast formation without consequent reduction in total cell number. Only gamma-tocotrienol inhibited osteoclast activity without toxicity. Gamma-tocotrienol was the most potent inhibitor of both osteoclast formation and activity and requires further investigation into its anti-resorptive effects on bone.
Brooks R, Kalia P, Ireland DC, Beeton C…
Int J Vitam Nutr Res Nov 2011
Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study.
The aim of this study was to evaluate the relationship between vitamin E status and osteoporosis in early postmenopausal women. Anthropometric data, osteoporosis risk factors, vitamin E serum levels, bone mineral density (BMD) and other serum parameters which may influence bone mineral density in postmenopausal women were analyzed in a cross-sectional study. The association between osteoporosis and age, age of menopause, body mass index, osteocalcin, calcium, vitamin D, vitamin E (measured as 25 hydroxyvitamin D and as α-tocopherol:lipids ratio, respectively), bone alkaline phosphatase, smoking status, leisure physical activity and alcohol intake were modeled by a multivariate logistic regression and multi-linear regression analysis in 232 early postmenopausal women. A lower vitamin E:lipid ratio was associated with osteoporosis in multivariate logistic regression. In a multivariate linear model with BMD of the lumbar spine as a dependent variable, the vitamin E:lipid ratio was clearly related with BMD of the lumbar spine (F ratio = 6.30, p = 0.002). BMD of the lumbar spine was significantly higher in the highest tertile of the vitamin E:lipid ratio than in the lowest tertile. The mean vitamin E:lipid ratio was significantly lower in osteoporotic postmenopausal women (T score ≤-2.5) (3.0 ± 0.6 μmol/mmol) than normal (neither osteoporotic nor osteopenic) postmenopausal women (T score >-1) (3.5 ± 0.7 μmol/mmol) using multivariable-adjusted BMD. These findings highlight that vitamin E may increase BMD in healthy postmenopausal women.
Mata-Granados JM, Cuenca-Acebedo R, Luque de Castro MD, Quesada Gómez JM
J. Bone Miner. Metab. Jul 2013
Oxidized low density lipoprotein inhibits phosphate signaling and phosphate-induced mineralization in osteoblasts. Involvement of oxidative stress.
It is well admitted that oxidized LDL (OxLDL) plays a major role in the generation and progression of atherosclerosis. Since atherosclerosis is often accompanied by osteoporosis, the effects of OxLDL on phosphate-induced osteoblast mineralization were investigated.
Calcium deposition, expression of osteoblast markers and inorganic phosphate (Pi) signaling were determined under OxLDL treatment.
OxLDL, within the range of 10-50 μg protein/ml, inhibited Pi-induced UMR106 rat osteoblast mineralization. In parallel, the expression of Cbfa1/Runx2 transcription factor was decreased, and the intracellular level of the osteoblast marker osteopontin (OPN) was reduced. The extracellular level of another marker, receptor activator of nuclear factor kappa B ligand (RANKL), was also diminished. OxLDL inhibited Pi signaling via ERK/JNK kinases and AP1/CREB transcription factors. OxLDL triggered the generation of reactive oxygen species (ROS), either in the absence or presence of Pi. Furthermore, the effects of OxLDL on Pi-induced mineralization, generation of ROS and extracellular level OPN were reproduced by the lipid extract of the particle, whereas the antioxidant vitamin E prevented them.
This work demonstrates that OxLDL, by generation of an oxidative stress, inhibits of Pi signaling and impairs Pi-induced osteoblast differentiation.
This highlights the role of OxLDL in bone remodeling and in degenerative disorders other than atherosclerosis, especially in osteoporosis.
Mazière C, Savitsky V, Galmiche A, Gomila C…
Biochim. Biophys. Acta Nov 2010
Beneficial effects of vitamin E isomer supplementation on static and dynamic bone histomorphometry parameters in normal male rats.
Bone is a specialized connective tissue that functions as the load-bearing structure of the body. Free radicals may affect bone remodeling by regulating osteoclast activity in either the physiological or pathological condition. Vitamin E, a lipid-soluble antioxidant, has been demonstrated to offer protection against osteoporosis and to improve the bone material and structure of animal models. The aim of this study was to observe and compare the effects of alpha-tocopherol (alpha-tocopherol), delta-tocotrienol (delta-tocotrienol), and gamma-tocotrienol (gamma-tocotrienol) on the static and dynamic bone histomorphometric parameters in normal male rats. Thirty-two normal Sprague-Dawley male rats aged 3 months and weighing 200-250 g were randomly divided into four groups. The control group was supplemented with oral gavages of olive oil (vehicle), whereas the alpha-tocopherol, delta-tocotrienol, and gamma-tocotrienol groups were given oral gavages of 60 mg/kg alpha-tocopherol, delta-tocotrienol, and gamma-tocotrienol, respectively. The rats were injected twice with calcein to fluorochrome-label the bones. After 4 months of treatment, the rats were killed, and the left femurs were dissected out and prepared for bone histomorphometry. Both the static and dynamic parameters of the vitamin E-treated groups were better than those of the normal control group. Among the vitamin E-treated groups, the tocotrienol groups showed better histomorphometry results compared to the α-tocopherol group, with the γ-tocotrienol group demonstrating the best effects on both sets of parameters. We concluded that vitamin E can promote bone formation in normal rats, with gamma-tocotrienol being the most potent form of vitamin E.
Mehat MZ, Shuid AN, Mohamed N, Muhammad N…
J. Bone Miner. Metab. Sep 2010
Tocotrienol supplementation improves late-phase fracture healing compared to alpha-tocopherol in a rat model of postmenopausal osteoporosis: a biomechanical evaluation.
This study investigated the effects of α-tocopherol and palm oil tocotrienol supplementations on bone fracture healing in postmenopausal osteoporosis rats. 32 female Sprague-Dawley rats were divided into four groups. The first group was sham operated (SO), while the others were ovariectomised. After 2 months, the right femora were fractured under anesthesia and fixed with K-wire. The SO and ovariectomised-control rats (OVXC) were given olive oil (vehicle), while both the alpha-tocopherol (ATF) and tocotrienol-enriched fraction (TEF) groups were given alpha-tocopherol and tocotrienol-enriched fraction, respectively, at the dose of 60 mg/kg via oral gavages 6 days per week for 8 weeks. The rats were then euthanized and the femora dissected out for bone biomechanical testing to assess their strength. The callous of the TEF group had significantly higher stress parameter than the SO and OVXC groups. Only the SO group showed significantly higher strain parameter compared to the other treatment groups. The load parameter of the OVXC and ATF groups was significantly lower than the SO group. There was no significant difference in the Young’s modulus between the groups. In conclusion, tocotrienol is better than α-tocopherol in improving the biomechanical properties of the fracture callous in postmenopausal osteoporosis rat model.
Mohamad S, Shuid AN, Mokhtar SA, Abdullah S…
Evid Based Complement Alternat Med 2012
PMID: 22829855 | Free Full Text
Effects of tocotrienol and lovastatin combination on osteoblast and osteoclast activity in estrogen-deficient osteoporosis.
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.
Abdul-Majeed S, Mohamed N, Soelaiman IN
Evid Based Complement Alternat Med 2012
PMID: 22927884 | Free Full Text
Palm tocotrienol exerted better antioxidant activities in bone than alpha-tocopherol.
The aim of this study was to investigate the effects of vitamin E on the levels of lipid peroxidation and antioxidant enzymes in rat bones. Fifty-six normal male Sprague-Dawley rats, aged 3 months, were randomly divided into seven groups with eight rats in each group. The age-matched control group was given the vehicle olive oil, by oral gavage daily. Six of the treatment groups received either palm tocotrienol or pure alpha-tocopherol at the dose of 30, 60 or 100 mg/kg body weight, by oral gavage daily, 6 days a week for 4 months. Thiobarbituric acid-reactive substance (TBARS) that is an index to measure the level of lipid peroxidation and the antioxidant enzymes, glutathione peroxidase and superoxide dismutase levels were measured in the femur at the end of the study. Palm tocotrienol at the dose of 100 mg/kg body weight significantly reduced the TBARS level in the femur with a significant increase in glutathione peroxidase activity compared to the age-matched control group. These were not observed in the alpha-tocopherol groups. Palm tocotrienol was more effective than pure alpha-tocopherol acetate in suppressing lipid peroxidation in bone. Palm tocotrienol showed better protective effect against free radical damage in the femur compared to alpha-tocopherol. This study suggests that palm tocotrienol plays an important role in preventing imbalance in bone metabolism due to free radicals.
Maniam S, Mohamed N, Shuid AN, Soelaiman IN
Basic Clin. Pharmacol. Toxicol. Jul 2008
Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone.
1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats.
2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines.
3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05).
4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.
Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S
Clin. Exp. Pharmacol. Physiol. Sep 2005
Tocotrienols are needed for normal bone calcification in growing female rats.
In this study the effects of vitamin E deficiency and supplementation on bone calcification were determined using 4-month-old female Sprague-Dawley rats. The rats weighed between 180 and 200 g. The study was divided in three parts. In experiment I the rats were given normal rat chow (RC, control group), a vitamin E deficient (VED) diet or a 50% vitamin E deficient (50%VED) diet. In experiment 2 the rats were given VED supplemented with 30 mg/kg palm vitamin E (PVE30), 60 mg/kg palm vitamin E (PVE60) or 30 mg/kg pure alpha-tocopherol (ATF). In experiment 3 the rats were fed RC and given the same supplements as in experiment 2. The treatment lasted 8 months. Vitamin E derived from palm oil contained a mixture of ATF and tocotrienols. Rats on the VED and 50%VED diets had lower bone calcium content in the left femur compared to the RC group (91.6 +/- 13.3 mg and 118.3 +/- 26.0 mg cf 165.7 +/- 15.2 mg; P < 0.05) and L5 vertebra (28.3 +/- 4.0 mg and 39.5 +/- 6.2 mg compared with 51.4 +/- 5.8 mg; P < 0.05). Supplementing the VED group with PVE60 improved bone calcification in the left femur (133.6 +/- 5.0 mg compared with 91.6 +/- 13.3 mg; P < 0.05) and L5 vertebra (41.3 +/- 3.3 mg compared with 28.3 +/- 4.0 mg; P < 0.05) while supplementation with PVE30 improved bone calcium content in the L5 vertebra (35.6 +/- 3.1 mg compared with 28.3 +/- 4.0 mg; P < 0.05). However, supplementation with ATF did not change the lumbar and femoral bone calcium content compared to the VED group. Supplementing the RC group with PVE30, PVE60 or ATF did not cause any significant changes in bone calcium content. In conclusion, vitamin E deficiency impaired bone calcification. Supplementation with the higher dose of palm vitamin E improved bone calcium content, but supplementation with pure ATF alone did not. This effect may be attributed to the tocotrienol content of palm vitamin E. Therefore, tocotrienols play an important role in bone calcification.
Norazlina M, Ima-Nirwana S, Abul Gapor MT, Abdul Kadir Khalid B
Asia Pac J Clin Nutr 2002
PMID: 12230232 | Free Full Text