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      A Histopathological, Immunohistochemical and Biochemical Investigation on the in vitro Antioxidant, Myeloprotective, Hematoprotective and Hepatoprotective Effects of Hypericum triquetrifolium Seed Extract Against Cyclophosphamide-Induced Toxicity

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          Abstract

          Abstract The aim of this study was to investigate in vitro antioxidant properties and in vivo protective effects of the methanol extract of the Hypericum triquetrifolium Turra (HT) seed against acute hepatotoxicity, myelotoxicity and hematotoxicity in rats induced by cyclophosphamide (CP). In order to investigate in vivo protective effects of the HT extract on rat tissues, the rats were divided into nine groups. The toxic effects of CP and the protective effects of HT extract on nucleated cells that are produced by bone marrow, serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and oxidative stress index (OSI) levels were investigated biochemically. Additionally, liver tissue samples were examined for histopathological changes and apoptosis by Bcl-2, Bax and caspase-3 immunohistochemistry. The results of this study show that HT seed methanol extract has high total phenolic content (179.52 μg GAE/mg) and antioxidant activity (87.48% in 500 μg/mL concentration). CP administration caused hepatotoxicity, myelotoxicity and hematotoxicity in the rats. Whereas, the groups of rats that were injected with different concentrations of HT (25, 50 and 100 mg/kg) and CP (150 mg/kg) showed significant protective effects on bone marrow nucleated cells and important decreases on serum ALT, ALP, LDH and OSI levels were observed when compared with the CP injected group.

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          Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NFκB/MAPK pathway.

          Cyclophosphamide is a potent anticancer agent. However its clinical use is restricted because of its marked organ toxicity associated with increased oxidative stress and inflammation. The present study was designed to demonstrate the protective effects of rutin, a naturally occurring bioflavonoid against the hepatotoxicity induced by CP. Rats were subjected to oral pretreatment of rutin (50 and 100 mg/kg b wt) against hepatotoxicity induced by i.p. injection of CP (150 mg/kg b wt) and were sacrificed after 24 h. Hepatoprotective effects of rutin were associated with upregulation of antioxidant enzyme activities and down regulation of serum toxicity markers. Rutin was able to down regulate the levels of inflammatory markers like TNF-α, IL-6 and expressions of p38-MAPK, NFκB, i-NOS and COX-2. Histopathological changes further confirmed the biochemical and immunohistochemical results showing that CP caused significant structural damage to liver which were reversed by pretreatment of rutin. Therefore, our study revealed that rutin may be a promising modulator in attenuating CP induced oxidative stress, inflammation and hepatotoxicity via targeting NFκB and MAPK pathway.
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            Total Phenol Analysis: Automation and Comparison with Manual Methods

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              Berberine mitigates cyclophosphamide-induced hepatotoxicity by modulating antioxidant status and inflammatory cytokines.

              The present study was designed to investigate the possible protective effects of berberine against cyclophosphamide (CP)-induced hepatotoxicity in rats.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                babt
                Brazilian Archives of Biology and Technology
                Braz. arch. biol. technol.
                Instituto de Tecnologia do Paraná - Tecpar (Curitiba, PR, Brazil )
                1516-8913
                1678-4324
                2019
                : 62
                : e19180345
                Affiliations
                [4] Eskisehir orgnameEskisehir Osmangazi University orgdiv1Science Faculty orgdiv2Department of Biology Turkey
                [2] Mardin orgnameMardin Artuklu University orgdiv1School of Health orgdiv2Department of Nutrition and Dietetics Turkey
                [3] Eskisehir orgnameEskisehir Osmangazi University orgdiv1Medical Faculty orgdiv2Department of Histology and Embryology Turkey
                [1] Mardin orgnameMardin Artuklu University orgdiv1Vocational Higher of Health Services orgdiv2Department of Medical Services and Techniques Turkey
                Article
                S1516-89132019000100303
                10.1590/1678-4324-2019180345
                21b36ff0-a5fc-435e-8528-83aa4cc422b8

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 06 July 2018
                : 19 May 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 41, Pages: 0
                Product

                SciELO Brazil

                Categories
                Article - Human and Animal Health

                hepatoprotective,cyclophosphamide,pharmacological activity,myeloprotective,Hypericum triquetrifolium,hematoprotective

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