Displaying publications 1 - 20 of 70 in total

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  1. Abdul-Majeed S, Mohamed N, Soelaiman IN
    Life Sci, 2015 Mar 15;125:42-8.
    PMID: 25534439 DOI: 10.1016/j.lfs.2014.12.012
    Statins are competitive inhibitors of HMGCoA reductase and are commonly used as antihypercholesterolemic agents. Experimental studies clearly demonstrate the beneficial effects of statins on bone. Tocotrienols have also been shown to have anti-osteoporotic effects on the skeletal system. This study was conducted to observe the effect of a combination of delta-tocotrienol and lovastatin on structural bone histomorphometry and bone biomechanical strength in a postmenopausal rat model at clinically tolerable doses, and to compare it with the effect of delta-tocotrienol or lovastatin.
  2. Chin KY, Mo H, Soelaiman IN
    Curr Drug Targets, 2013 Dec;14(13):1533-41.
    PMID: 23859472
    Osteoporosis is posing a tremendous healthcare problem globally. Much effort has been invested in finding novel antiosteoporotic agents to stop the progression of this disease. Tocotrienol, one of the isoforms of vitamin E, is poised as a potential antiosteoporotic agent. Previous studies showed that tocotrienol as a single isomer or as a mixture demonstrated both anabolic and antiresorptive effects in various rodent models of osteoporosis. In vitro experiments further demonstrated that tocotrienol could up-regulate genes related to osteoblastogenesis and modify receptor activator of nuclear factor kappa B signaling against osteoclastogenesis. Additionally, tocotrienol was also shown to be a strong 3- hydroxy-3-methyl-glutaryl-CoA reductase down-regulator with a mechanism different from that of statins. Inhibition of the mevalonate pathway affects both osteoblast and osteoclast formation in favor of the former. Tocopherol, a more commonly used isoform of vitamin E does not possess similar effects. Tocotrienol is also a potent antioxidant. It can scavenge free radicals and prevent oxidative damage on osteoblast thus promoting its survival. It may also up-regulate the antioxidant defense network in osteoclast and indirectly act against free radical signaling essential in osteoclastogenesis. The effects of tocotrienol on Wnt/β-catenin signaling essential in osteoblastogenesis have not been determined. More mechanistic studies need to be conducted to illustrate the antiosteoporotic effects of tocotrienol. Clinical trials are also required to confirm its effects in humans. In conclusion, tocotrienol demonstrates great potential as an antiosteoporotic agent and much research effort should be invested to develop it as an agent to curb osteoporosis.
  3. Abdul-Majeed S, Mohamed N, Soelaiman IN
    Curr Drug Targets, 2013 Dec;14(13):1579-90.
    PMID: 23848479
    Skeletal tissue undergoes continuous remodeling which makes it unique among other body tissues. Osteoporosis is a common bone metabolic disorder affecting both men and women. Osteoporosis and its complications mainly osteoporotic fractures, have a high impact on health and economy. Current approved medications are associated with numerous side effects, which limit their use. Identification of a new and safe therapy is mandatory. Statins, also known as HMGCoA reductase inhibitors, are frequently used for the treatment of hypercholesterolemia and for the prevention of morbidity and mortality associated with cardiovascular disease. Statins improved bone health status in intact and ovariectomised rodents following high clinically intolerable oral doses. However, this beneficial effect of statins could not be significantly demonstrated in humans. The reason behind this discrepancy might be due to the safety and bioavailability of the currently used oral statins. Vitamin E, especially the tocotrienols at the dose 60 mg/kg/day provided significant antiosteoporotic effects in different animal models of osteoporosis. The use of the aforementioned dose of tocotrienols was shown to be safe in both humans and animals. Enhancement of bone formation and reduction of bone resorption were achieved more effectively by a combination of tocotrienols and statins than by either treatment when supplemented separately at clinically tolerable doses. Therefore, the adverse effects associated with high statin doses might be avoided with the coadministration of tocotrienols. Moreover, the combination therapy strategy might be useful for patients who are at high risk of osteoporosis, cardiovascular events and hypercholesterolaemia.
  4. Abdul-Majeed S, Mohamed N, Soelaiman IN
    PMID: 22927884 DOI: 10.1155/2012/960742
    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.
  5. Soelaiman IN, Merican Z, Mohamed J, Kadir KB
    Asia Pac J Clin Nutr, 1996 Dec;5(4):244-8.
    PMID: 24394618
    We determined the relative atherogenicity of two saturated fats by studying their effects on lipid peroxidation (LP), by way of malonaldehyde (MDA) and conjugated dienes (CD) and glutathione peroxidase (GSHPx) activity in serum, liver and heart; and on serum lipid profile after 4 months and 9 months of feeding. Male Rattus norwegicus rats were fed a basal diet (control) or basal diet fortified with 20% weight/weight butterfat (ghee) (BF) or coconut oil (CO). Serum high-density-lipoprotein-cholesterol (HDL-chol) and HDL-chol:LDL-chol ratio was lower in the BF group compared to CO after both feeding periods. Conjugated dienes (CDs) were higher in the serum and liver after 4 months, and heart after 9 months, of the rats fed BF compared to CO. Serum low-density-lipoprotein-cholesterol (LDL-chol) was higher, but CD were lower at 9 months than at 4 months feeding for all three groups. Liver and heart MDA and CD were higher in both groups after 9 months compared to 4 months. Liver GSHPx activity was higher after 9 months compared to 4 months in the BF group. Heart GSHPx activity was lower after 9 months compared to 4 months for both BF and CO groups. In conclusion, BF is potentially more atherogenic than CO in terms of serum lipids and LP. The unfavourable responses in serum lipids, with the exception of triglycerides, and LP were exaggerated with the longer duration of feeding with both oils.
  6. Mohamad NV, Soelaiman IN, Chin KY
    Clin Interv Aging, 2016;11:1317-1324.
    PMID: 27703340
    Osteoporosis is a condition causing significant morbidity and mortality in the elderly population worldwide. Age-related testosterone deficiency is the most important factor of bone loss in elderly men. Androgen can influence bone health by binding to androgen receptors directly or to estrogen receptors (ERs) indirectly via aromatization to estrogen. This review summarized the direct and indirect effects of androgens on bone derived from in vitro, in vivo, and human studies. Cellular studies showed that androgen stimulated the proliferation of preosteoblasts and differentiation of osteoblasts. The converted estrogen suppressed osteoclast formation and resorption activity by blocking the receptor activator of nuclear factor k-B ligand pathway. In animal studies, activation of androgen and ERα, but not ERβ, was shown to be important in acquisition and maintenance of bone mass. Human epidemiological studies demonstrated a significant relationship between estrogen and testosterone in bone mineral density and fracture risk, but the relative significance between the two remained debatable. Human experimental studies showed that estrogen was needed in suppressing bone resorption, but both androgen and estrogen were indispensable for bone formation. As a conclusion, maintaining optimal level of androgen is essential in preventing osteoporosis and its complications in elderly men.
  7. Mohamad NV, Soelaiman IN, Chin KY
    Biomed Pharmacother, 2018 Jul;103:453-462.
    PMID: 29674281 DOI: 10.1016/j.biopha.2018.04.083
    INTRODUCTION: Osteoporosis is a debilitating skeletal side effect of androgen deprivation therapy based on gonadotropin-releasing hormone (GnRH) agonist in men. Tocotrienol from Bixa orellana (annatto) has been demonstrated to offer protection against osteoporosis by exerting anabolic effects on bone. Thus, it may prevent osteoporosis among GnRH agonist users.

    OBJECTIVE: This study aimed to determine the effectiveness of annatto-tocotrienol on the bone turnover markers and bone histomorphometry in a model of male osteoporosis induced by buserelin (a GnRH agonist).

    METHODS: Forty-six three-months-old male Sprague-Dawley rats (three months old; 300-350 g) were randomly divided into six groups. The baseline control group (n = 6) was sacrificed at the onset of the study. The normal control group (n = 8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n = 8) received corn oil orally daily and subcutaneous buserelin injection 75 μg/kg/day daily. The calcium control (n = 8) received 1% calcium in drinking water and subcutaneous buserelin injection 75 μg/kg/day. The remaining rats were treated with two different treatments, i.e., (1) oral annatto tocotrienol at 60 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8); (2) oral annatto tocotrienol at 100 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8). The rats were injected with calcein twice before being sacrificed to label the bones. The rats were euthanized, and their blood and right femur were harvested at the end of the treatment for bone turnover markers and bone histomorphometry examination.

    RESULTS: Both serum osteocalcin and C-telopeptide of type 1 collagen were not significantly different between treated groups and buserelin control (P > 0.05). The buserelin control group had a significantly lower bone volume and higher eroded surface compared with the normal control group (P 

  8. Chin KY, Pang KL, Soelaiman IN
    Adv Exp Med Biol, 2016;928:97-130.
    PMID: 27671814
    Tocotrienol is a member of vitamin E family and is well-known for its antioxidant and anti-inflammatory properties. It is also a suppressor of mevalonate pathway responsible for cholesterol and prenylated protein synthesis. This review aimed to discuss the health beneficial effects of tocotrienol, specifically in preventing or treating hyperlipidaemia, diabetes mellitus, osteoporosis and cancer with respect to these properties. Evidence from in vitro, in vivo and human studies has been examined. It is revealed that tocotrienol shows promising effects in preventing or treating the health conditions previously mentioned in in vivo and in vitro models. In some cases, alpha-tocopherol attenuates the biological activity of tocotrienol. Except for its cholesterol-lowering effects, data on the health-promoting effects of tocotrienol in human are limited. As a conclusion, the encouraging results on the health beneficial effects of tocotrienol should motivate researchers to explore its potential use in human.
  9. Mohamad NV, Soelaiman IN, Chin KY
    Endocr Metab Immune Disord Drug Targets, 2017 Nov 16;17(4):276-284.
    PMID: 28925899 DOI: 10.2174/1871530317666170919112757
    BACKGROUND AND OBJECTIVE: Prostate cancer is the most prevalent non-cutaneous cancer in men, which causes significant mortality among the patients. Since prostate cancer cells are stimulated by androgen, effective androgen ablation in men is one of the essential strategies in the management of prostate cancer.

    DISCUSSION: Several treatment options are available for different stages of prostate cancer. Hormone therapy known as androgen deprivation therapy (ADT) is the first line treatment used to treat advanced prostate cancer. Chemical castration by gonadotropin-releasing hormone agonists suppresses lutenizing hormone production, which in turn inhibits the production of testosterone and dihydrotestosterone. This will prevent the growth of prostate cancer cells. However, ADT causes deleterious effects on bone health because the androgens are essential in preserving optimal bone health in men.

    CONCLUSION: Various observational studies showed that long-term ADT for advanced or metastatic prostate cancer was associated with decreased bone mineral density, as well as altered body composition that might affect bone health. Considering the potential impact of osteoporotic fracture, interventions to mitigate these skeletal adverse effects should be considered by physicians when initiating ADT on their patients.

  10. Effendy NM, Khamis MF, Soelaiman IN, Shuid AN
    J Xray Sci Technol, 2014;22(4):503-18.
    PMID: 25080117 DOI: 10.3233/XST-140441
    Postmenopausal osteoporosis is best treated and prevented by estrogen replacement therapy (ERT). Although effective, ERT may cause breast cancer, uterine cancer and cardiovascular problems. Labisia pumila var. alata (LP), a herb with phytoestrogenic, antioxidative and anti-inflammatory effects has potential as an ERT alternative.
  11. Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman IN
    Clinics (Sao Paulo), 2013 Oct;68(10):1338-43.
    PMID: 24212841 DOI: 10.6061/clinics/2013(10)08
    OBJECTIVE: Accelerated bone loss that occurs in postmenopausal women has been linked to oxidative stress and increased free radicals. We propose the use of antioxidants to prevent and reverse postmenopausal osteoporosis. This study aimed to examine the effects of tocotrienol, a vitamin E analog, on bone loss due to estrogen deficiency. Our previous study showed that tocotrienol increased the trabecular bone volume and trabecular number in ovariectomized rats. In the current study, we investigated the effects of tocotrienol supplementation on various biochemical parameters in a postmenopausal osteoporosis rat model.
    MATERIALS AND METHODS: A total of 32 female Wistar rats were randomly divided into four groups. The baseline group was sacrificed at the start of the study, and another group was sham operated. The remaining rats were ovariectomized and either given olive oil as a vehicle or treated with tocotrienol at a dose of 60 mg/kg body weight. After four weeks of treatment, blood was withdrawn for the measurement of interleukin-1 (IL1) and interleukin-6 (IL6) (bone resorbing cytokines), serum osteocalcin (a bone formation marker) and pyridinoline (a bone resorption marker).
    RESULTS: Tocotrienol supplementation in ovariectomized rats significantly reduced the levels of osteocalcin, IL1 and IL6. However, it did not alter the serum pyridinoline level.
    CONCLUSION: Tocotrienol prevented osteoporotic bone loss by reducing the high bone turnover rate associated with estrogen deficiency. Therefore, tocotrienol has the potential to be used as an anti-osteoporotic agent in postmenopausal women.
  12. Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman IN
    PMID: 23118785 DOI: 10.1155/2012/161527
    Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function, a condition associated with increased free radicals. Vitamin E, a lipid-soluble vitamin, is a potent antioxidant which can scavenge free radicals in the body. In this study, we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats. Three-month-old female Wistar rats were randomly divided into ovariectomized control, sham-operated, and ovariectomized rats treated with either alpha-tocopherol or tocotrienol. Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis. Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume (BV/TV) and trabecular number (Tb.N) and an increase in trabecular separation (Tb.S). The increase in osteoclast surface (Oc.S) and osteoblast surface (Ob.S) in ovariectomy indicates an increase in bone turnover rate. Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb.N as well as the increase in Tb.S, while reducing the Oc.S and increasing the Ob.S. In conclusion, the two forms of vitamin E were able to prevent bone loss due to ovariectomy. Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model.
  13. Hayatullina Z, Muhammad N, Mohamed N, Soelaiman IN
    PMID: 23024690
    Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO) on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx), and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO). Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model.
  14. Abujazia MA, Muhammad N, Shuid AN, Soelaiman IN
    PMID: 22927879 DOI: 10.1155/2012/525079
    Virgin coconut oil (VCO) was found to have antioxidant property due to its high polyphenol content. The aim of this study was to investigate the effect of the virgin coconut oil on lipid peroxidation in the bone of an osteoporotic rat model. Normal female Sprague-Dawley rats aged 3 months old were randomly divided into 4 groups, with 8 rats in each group: baseline, sham, ovariectomised (OVX) control group, and OVX given 8% VCO in the diet for six weeks. The oxidative status of the bone was assessed by measuring the index of lipid peroxidation, which is malondialdehyde (MDA) concentration, as well as the endogenous antioxidant enzymes glutathione peroxidase (GPX) and superoxide dismutase (SOD) in the tibia at the end of the study. The results showed that there was a significant decrease in MDA levels in the OVX-VCO group compared to control group. Ovariectomised rats treated with VCO also had significantly higher GPX concentration. The SOD level seemed to be increased in the OVX-VCO group compared to OVX-control group. In conclusion, VCO prevented lipid peroxidation and increased the antioxidant enzymes in the osteoporotic rat model.
  15. Tajul Ariff AS, Soelaiman IN, Pramanik J, Shuid AN
    PMID: 22966245 DOI: 10.1155/2012/818072
    Testosterone replacement is the choice of treatment in androgen-deficient osteoporosis. However, long-term use of testosterone is potentially carcinogenic. Eurycoma longifolia (EL) has been reported to enhance testosterone level and prevent bone calcium loss but there is a paucity of research regarding its effect on the bone structural parameters. This study was conducted to explore the bone structural changes following EL treatment in normal and androgen-deficient osteoporosis rat model. Thirty-six male Sprague-Dawley rats aged 12 months were divided into normal control, normal rat supplemented with EL, sham-operated, orchidectomised-control, orchidectomised with testosterone replacement, and orchidectomised with EL supplementation groups. Testosterone serum was measured both before and after the completion of the treatment. After 6 weeks of the treatment, the femora were processed for bone histomorphometry. Testosterone replacement was able to raise the testosterone level and restore the bone volume of orchidectomised rats. EL supplementation failed to emulate both these testosterone actions. The inability of EL to do so may be related to the absence of testes in the androgen deficient osteoporosis model for EL to stimulate testosterone production.
  16. Mohamad S, Shuid AN, Mokhtar SA, Abdullah S, Soelaiman IN
    PMID: 22829855 DOI: 10.1155/2012/372878
    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.
  17. Chin KY, Soelaiman IN, Mohamed IN, Ngah WZ
    Clinics (Sao Paulo), 2012 Aug;67(8):911-6.
    PMID: 22948459
    OBJECTIVES: Variations in sex hormones and the calcium balance can influence bone health in men. The present study aimed to examine the relationship between the calcaneal speed of sound and biochemical determinants of bone mass, such as sex hormones, parathyroid hormones and serum calcium.

    METHODS: Data from 549 subjects from the Malaysian Aging Male Study, which included Malay and Chinese men aged 20 years and older residing in the Klang Valley, were used for analysis. The subjects' calcaneal speed of sound was measured, and their blood was collected for biochemical analysis. Two sets of multiple regression models were generated for the total/bioavailable testosterone and estradiol to avoid multicollinearity.

    RESULTS: The multiple regression results revealed that bioavailable testosterone and serum total calcium were significant predictors of the calcaneal speed of sound in the adjusted model. After adjustment for ethnicity and body mass index, only bioavailable testosterone remained significant; the total serum calcium was marginally insignificant. In a separate model, the total testosterone and sex hormone-binding globulin were significant predictors, whereas the total serum calcium was marginally insignificant. After adjustment for ethnicity and body mass index (BMI), the significance persisted for total testosterone and SHBG. After further adjustment for age, none of the serum biochemical determinants was a significant predictor of the calcaneal speed of sound.

    CONCLUSION: There is a significant age-dependent relationship between the calcaneal speed of sound and total testosterone, bioavailable testosterone and sex hormone-binding globulin in Chinese and Malay men in Malaysia. The relationship between total serum calcium and calcaneal speed of sound is ethnicity-dependent.

  18. Hapidin H, Othman F, Soelaiman IN, Shuid AN, Mohamed N
    Calcif. Tissue Int., 2011 Jan;88(1):41-7.
    PMID: 20953592 DOI: 10.1007/s00223-010-9426-4
    Nicotine is a major alkaloid of tobacco, which can increase free radical formation, leading to osteoporosis. The effects of nicotine administration and cessation on bone histomorphometry and biomarkers were studied in 28 Sprague-Dawley male rats. Rats aged 3 months and weighing 250-300 g were divided into four groups: control (C, normal saline for 4 months), nicotine for 2 months (N2), nicotine for 4 months (N4), and nicotine cessation (NC). The NC group was given nicotine for the first 2 months and then allowed to recover for the following 2 months without nicotine. Histomorphometric analysis was done using an image analyzer. ELISA kits were used to measure serum osteocalcin (bone formation marker) and pyridinoline (PYD, bone resorption marker) levels at month 0, month 2, and month 4. All test groups showed a significant decrease in BV/TV, Ob.S/BS, dLS/BS, MAR, BFR/BS, and osteocalcin levels and an increase in sLS/BS and PYD levels compared to group C. No significant differences were observed in all parameters measured among the test groups, except for MAR and BFR/BS. In conclusion, nicotine administration at a dose of 7 mg/kg for 2 and 4 months has detrimental effects on bone metabolism. Nicotine administration at 7 mg/kg for 2 months is sufficient to produce significant effects on bone histomorphometric parameters and biomarkers. In addition, prolonging the treatment for another 2 months did not show any significant differences. Cessation of nicotine for 2 months did not reverse the effects.
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