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      Neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn.) leaf in male Wistar rat model of cyclophosphamide-induced reproductive toxicity

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          Abstract

          Cyclophosphamide (CP) is a widely used cytotoxic alkylating agent with antitumor and immunosuppressant properties that is associated with various forms of reproductive toxicity. The significance of natural antioxidants of plant origin should be explored, especially in a world with increasing incidence of patients in need of chemotherapy. The neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn.) leaf (AEAVL) in Wistar rats with CP-induced reproductive toxicity was determined. Forty rats were used for this study such that graded doses of the extract were administered following CP-induced reproductive toxicity and comparisons were made against control, toxic and standard (vitamin E) groups at p < 0.05. The synthetic drugs (CP, 65 mg/kg i.p. for 5 days; Vitamin E, 100 mg/kg p.o. for 30 days) as well as the extract (100, 200 and 400 mg/kg p.o. for 30 days) were administered to the rats at 0.2 mL/100 g. CP induced reproductive toxicity as evidenced by significantly lowered levels of FSH, LH and testosterone, perturbation of sperm characterization, deleterious disruptions of the antioxidant system as evidenced by decreased levels of GSH as well as elevation of TBARS activity. Histopathological examination showed hemorrhagic lesions with scanty and hypertrophied parenchymal cells in the pituitary while the testis showed ballooned seminiferous tubules with loosed connective tissues and vacuolation of testicular interstitium. These conditions were significantly reversed (p < 0.05) following administration of the graded doses of the extract. It was, therefore, concluded that AEAVL could potentially be a therapeutic choice in patients with CP-induced neuro-endocrine dysfunction and reproductive toxicity.

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          Vitamin E: function and metabolism.

          Although vitamin E has been known as an essential nutrient for reproduction since 1922, we are far from understanding the mechanisms of its physiological functions. Vitamin E is the term for a group of tocopherols and tocotrienols, of which alpha-tocopherol has the highest biological activity. Due to the potent antioxidant properties of tocopherols, the impact of alpha-tocopherol in the prevention of chronic diseases believed to be associated with oxidative stress has often been studied, and beneficial effects have been demonstrated. Recent observations that the alpha-tocopherol transfer protein in the liver specifically sorts out RRR-alpha-tocopherol from all incoming tocopherols for incorporation into plasma lipoproteins, and that alpha-tocopherol has signaling functions in vascular smooth muscle cells that cannot be exerted by other forms of tocopherol with similar antioxidative properties, have raised interest in the roles of vitamin E beyond its antioxidative function. Also, gamma-tocopherol might have functions apart from being an antioxidant. It is a nucleophile able to trap electrophilic mutagens in lipophilic compartments and generates a metabolite that facilitates natriuresis. The metabolism of vitamin E is equally unclear. Excess alpha-tocopherol is converted into alpha-CEHC and excreted in the urine. Other tocopherols, like gamma- and delta-tocopherol, are almost quantitatively degraded and excreted in the urine as the corresponding CEHCs. All rac alpha-tocopherol compared to RRR-alpha-tocopherol is preferentially degraded to alpha-CEHC. Thus, there must be a specific, molecular role of RRR-alpha-tocopherol that is regulated by a system that sorts, distributes, and degrades the different forms of vitamin E, but has not yet been identified. In this article we try to summarize current knowledge on the function of vitamin E, with emphasis on its antioxidant vs. other properties, the preference of the organism for RRR-alpha-tocopherol, and its metabolism to CEHCs.
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            Biological actions of androgens.

            Though unnecessary for life itself, androgens are essential for the propagation of the species and for establishment and maintenance of the quality of life of males through their support of sexual behavior and function, muscle strength, and sense of well-being. In carrying out its many functions, T acts both as hormone and prohormone. It is an outstanding example of the diverse evolutionary utilization of a primitive informational molecule both among and within species. Not only does T act through the androgen receptor both unchanged and via 5 alpha-reduction, but it acts in tissues with a high aromatase level as an estrogen via the estrogen receptor. Furthermore, DHT, binding to the estrogen receptor, can act as an inhibitor of estrogen action. The products of androgen metabolism may also play active regulatory roles in hematopoiesis and in the regulation of certain hepatic enzymes. Table 3 summarizes the actions of secreted T in males indicating the probable effector hormone. While gross hypogonadism is uncommon, mild androgen insufficiency may be much more frequent, especially in older men, and in those receiving treatment for chronic medical conditions. It is quite possible that such individuals would benefit from appropriate androgen therapy were it available, but the current forms of replacement therapy are not very satisfactory. Better approaches are required. With the exception of a small number of secreted proteins, the products of transcription induced by androgens are not, as yet, known. When the androgen receptor gene is cloned it will be possible to identify androgen-regulated genes and their products. It will then be possible to design agents selectively producing specific desired androgenic effects.
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              Bioaccessibility of carotenoids and vitamin E from their main dietary sources.

              Vitamin E and carotenoids are fat-soluble microconstituents that may exert beneficial effects in humans, including protection against cancer, cardiovascular diseases, and age-related eye diseases. Their bioavailability is influenced by various factors including food matrix, formulation, and food processing. Since human studies are labor-intensive, time-consuming, and expensive, the in vitro model used in this study is increasingly being used to estimate bioaccessibility of these microconstituents. However, the ability of this model to predict bioavailability in a healthy human population has not yet been verified. The first aim of this study was to validate this model by comparing model-derived bioaccessibility data with (i) human-derived bioaccessibility data and (ii) published mean bioavailability data reported in studies involving healthy humans. The second aim was to use it to measure alpha- and gamma-tocopherol, beta-carotene, lycopene, and lutein bioaccessibility from their main dietary sources. Bioaccessibility as assessed with the in vitro model was well correlated with human-derived bioaccessibility values (r = 0.90, p beta-carotene and alpha-carotene > lycopene and alpha-tocopherol generally > gamma-tocopherol), (ii) food matrix, and (iii) food processing.
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                Author and article information

                Contributors
                Journal
                Toxicol Rep
                Toxicol Rep
                Toxicology Reports
                Elsevier
                2214-7500
                03 August 2016
                2016
                03 August 2016
                : 3
                : 608-619
                Affiliations
                [a ]Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
                [b ]Department of Medical Laboratory Sciences, College of Medicine, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria
                Author notes
                [* ]Corresponding author at: Department of Physiological Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.Department of Physiological SciencesFaculty of Basic Medical SciencesObafemi Awolowo UniversityIle-IfeOsun StateNigeria staywithchris@ 123456gmail.com
                Article
                S2214-7500(16)30056-7
                10.1016/j.toxrep.2016.07.007
                5616021
                b2ac08db-5972-4df7-a094-423447247c7e
                © 2016 Published by Elsevier Ireland Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 June 2016
                : 21 July 2016
                : 30 July 2016
                Categories
                Article

                cyclophosphamide,neuro-endocrine dysfunction,reproductive toxicity,rats,amaranthus viridis

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