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      Osteocyte viability and bone density in cadmium chloride‐induced osteoporosis ameliorated with Pilostigma thonningii stem bark‐extracted D‐3‐O‐methy‐chiroinositol

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          Abstract

          Background

          This study examined the ameliorative effect of D‐3‐O‐methyl‐chiroinositol, isolated from the stem bark of Piliostigma thonningii, on cadmium chloride‐induced osteoporosis in male Wistar rats.

          Methods

          Thirty‐six rats were assigned to three treatment groups (n = 12). Group A (2 mL distilled water), group B: (2.5 mg/kg b.w. CdCl 2) and group C: (2.5 mg/kg b.w. CdCl 2 and D‐3‐O‐methyl‐chiroinositol 2 mg/kg b.w.). Bone ash, calcium, phosphate, magnesium, and zinc content, as well as bone histological changes were determined at the end of months 1, 2, and 3.

          Results

          There were significant differences ( ≤ 0.05) in the weight of the cervical, tibia, and femoral bones in all groups. The serum concentration of CdCl 2 was significantly different across the three groups with time. There was significant variation ( < 0.005) in the mean bone ash across groups. The concentration of OH‐proline was significantly different ( < 0.0001) across groups. There were significant differences ( < 0.0001) in bone calcium, magnesium, zinc, and phosphorus concentrations. Histology revealed high levels of bone mineralisation in the CdCl 2‐treated group, indicative of osteoporosis with hypertrophied osteocytes, while the femur of Wistar rats treated with D‐3‐O‐methyl‐chiroinositol showed bone trabeculae and viable osteocytes.

          Conclusion

          The study concluded that D‐3‐O‐methyl‐chiroinositol extract from Piliostigma thionningii stem bark ameliorated cadmium chloride‐induced osteoporosis in male Wistar rats.

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          Most cited references29

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          Metals, toxicity and oxidative stress.

          Metal-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen and nitrogen species, is reviewed. Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical thiols, however, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. However, a recent discovery that the upper limit of "free pools" of copper is far less than a single atom per cell casts serious doubt on the in vivo role of copper in Fenton-like generation of free radicals. Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition. Various studies have confirmed that metals activate signalling pathways and the carcinogenic effect of metals has been related to activation of mainly redox-sensitive transcription factors, involving NF-kappaB, AP-1 and p53. Antioxidants (both enzymatic and non-enzymatic) provide protection against deleterious metal-mediated free radical attacks. Vitamin E and melatonin can prevent the majority of metal-mediated (iron, copper, cadmium) damage both in vitro systems and in metal-loaded animals. Toxicity studies involving chromium have shown that the protective effect of vitamin E against lipid peroxidation may be associated rather with the level of non-enzymatic antioxidants than the activity of enzymatic antioxidants. However, a very recent epidemiological study has shown that a daily intake of vitamin E of more than 400 IU increases the risk of death and should be avoided. While previous studies have proposed a deleterious pro-oxidant effect of vitamin C (ascorbate) in the presence of iron (or copper), recent results have shown that even in the presence of redox-active iron (or copper) and hydrogen peroxide, ascorbate acts as an antioxidant that prevents lipid peroxidation and does not promote protein oxidation in humans in vitro. Experimental results have also shown a link between vanadium and oxidative stress in the etiology of diabetes. The impact of zinc (Zn) on the immune system, the ability of zinc to act as an antioxidant in order to reduce oxidative stress and the neuroprotective and neurodegenerative role of zinc (and copper) in the etiology of Alzheimer's disease is also discussed. This review summarizes recent findings in the metal-induced formation of free radicals and the role of oxidative stress in the carcinogenicity and toxicity of metals.
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            Cadmium-Induced Effects on Bone in a Population-Based Study of Women

            High cadmium exposure is known to cause bone damage, but the association between low-level cadmium exposure and osteoporosis remains to be clarified. Using a population-based women’s health survey in southern Sweden [Women’s Health in the Lund Area (WHILA)] with no known historical cadmium contamination, we investigated cadmium-related effects on bone in 820 women (53–64 years of age). We measured cadmium in blood and urine and lead in blood, an array of markers of bone metabolism, and forearm bone mineral density (BMD). Associations were evaluated in multiple linear regression analysis including information on the possible confounders or effect modifiers: weight, menopausal status, use of hormone replacement therapy, age at menarche, alcohol consumption, smoking history, and physical activity. Median urinary cadmium was 0.52 μg/L adjusted to density (0.67 μg/g creatinine). After multivariate adjustment, BMD, parathyroid hormone, and urinary deoxypyridinoline (U-DPD) were adversely associated with concentrations of urinary cadmium (p < 0.05) in all subjects. These associations persisted in the group of never-smokers, which had the lowest cadmium exposure (mainly dietary). For U-DPD, there was a significant interaction between cadmium and menopause (p = 0.022). Our results suggest negative effects of low-level cadmium exposure on bone, possibly exerted via increased bone resorption, which seemed to be intensified after menopause. Based on the prevalence of osteoporosis and the low level of exposure, the observed effects, although slight, should be considered as early signals of potentially more adverse health effects.
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              Cadmium, osteoporosis and calcium metabolism.

              Occupational exposure to cadmium has for long been associated with renal tubular cell dysfunction, osteomalacia with osteoporosis, hypercalciuria and renal stone formation. High environmental exposure in Japan resulting from a stable diet of cadmium contaminated rice caused itai-itai disease, fractures occurring mainly in elderly multiparous women, with a form of osteomalacia, osteoporosis and renal dysfunction. More recently a population based study in Europe, in the vicinity of zinc smelters has shown that low to moderate exposure to cadmium, with a mean urinary excretion of cadmium of the order of 1 microg/g creatinine has been associated with a decrease in bone density, an increased risk of bone fractures in women and of height loss in men. In a population-based study of residents near a cadmium smelter in China, forearm bone density was shown to decrease linearly with age and urinary cadmium in both sexes, suggesting a dose effect relationship between cadmium dose and bone mineral density. A marked increase in the prevalence of fractures was shown in the cadmium-polluted area in both sexes. Concentrations of cadmium in blood and urine were taken as exposure biomarkers, and beta2-microglobulin, retinol binding protein and albumin as biomarkers of effect. A marked dose response relationship between these indicators of exposure and effect was shown. Hypercalciuria, which may progress to osteoporosis, has been taken as a sensitive renal-tubular biomarker of a low level of cadmium exposure. Cadmium may also act directly on bone. Animal studies have shown cadmium to stimulate the formation and activity of osteoclasts, breaking down the collagen matrix in bone. Osteoporosis is the main cause of fracures in post-menopausal women, a common occurrence worldwide, giving rise to disability and a high cost to health services. The identification of cadmium, an environmental pollutant, as one causal factor is highly significant in helping to control the incidence of this complex condition.
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                Author and article information

                Contributors
                edwin.uwagie-ero@uniben.edu
                Journal
                Animal Model Exp Med
                Animal Model Exp Med
                10.1002/(ISSN)2576-2095
                AME2
                Animal Models and Experimental Medicine
                John Wiley and Sons Inc. (Hoboken )
                2096-5451
                2576-2095
                20 February 2019
                March 2019
                : 2
                : 1 ( doiID: 10.1002/ame2.2019.2.issue-1 )
                : 25-33
                Affiliations
                [ 1 ] Department of Surgery Faculty of Veterinary Medicine University of Benin Benin City Nigeria
                [ 2 ] Department of Anatomy Faculty of Veterinary Medicine University of Nigeria Nsukka Nigeria
                [ 3 ] Department of Biochemistry College of Basic Medical Sciences University of Calabar Calabar Nigeria
                [ 4 ] Department of Surgery Faculty of Veterinary Medicine University of Nigeria Nsukka Nigeria
                [ 5 ] Department of Anatomy Faculty of Veterinary Medicine University of Benin Benin City Nigeria
                [ 6 ] Department of Physiology and Biochemistry Faculty of Veterinary Medicine University of Benin Benin City Nigeria
                Author notes
                [*] [* ] Correspondence

                Edwin Aihanuwa Uwagie‐Ero, Department of Surgery, Faculty of Veterinary Medicine, University of Benin, Benin City, Nigeria.

                Email: edwin.uwagie-ero@ 123456uniben.edu

                Author information
                https://orcid.org/0000-0001-6945-2169
                Article
                AME212054
                10.1002/ame2.12054
                6431122
                294d277f-546b-4ebe-b6bd-819901edf418
                © 2019 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 02 October 2018
                : 23 December 2018
                Page count
                Figures: 10, Tables: 3, Pages: 9, Words: 5329
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                ame212054
                March 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.1 mode:remove_FC converted:23.03.2019

                cadmium chloride,d‐3‐o‐methyl‐chiroinositol,osteocytes,osteoporosis,toxicity, amelioration

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