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      Hepatoprotective Effect of the Aqueous Extract of Simarouba amara Aublet (Simaroubaceae) Stem Bark against Carbon Tetrachloride (CCl 4)-Induced Hepatic Damage in Rats

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          Abstract

          Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on CCl 4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group). Groups I (vehicle—corn oil), II (control-CCl 4), III, IV, V and VI were pretreated during 10 consecutive days, once a day p.o, with Legalon ® 50 mg/kg b.w, SAAE at doses 100, 250 and 500 mg/kg b.w, respectively. The hepatotoxicity was induced on 11th day with 2 mL/kg of 20% CCl 4 solution. 24 h after injury, the blood samples were collected and their livers were removed to biochemical and immunohistochemical analyzes. The SAAE decreased the levels of liver markers and lipid peroxidation in all doses and increased the catalase levels at doses 250 and 500 mg/kg. Immunohistochemical results suggested hepatocyte proliferation in all doses. These results may be related to catechins present in SAAE. Thus, SAAE prevented the oxidative damage at the same time that increased regenerative and reparative capacities of the liver.

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          Most cited references24

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          Mechanisms of carbon tetrachloride toxicity

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            Systematics and health effects of chemically distinct tannins in medicinal plants.

            The research began with an investigation of tannins from traditional medicinal plants and resulted in isolation and structure determination of hundreds of ellagitannins and dehydroellagitannins, as well as their oligomers and oxidized derivatives with various structures specific to each plant species. These polyphenols have been classified according to the stage of oxidative structural transformation and oligomerization, into types I-IV and I+ to IV+, etc. Parallels were found between their oxidative transformations and plant evolution. They were also classified by the linkage units between the monomers, into DOG, GOD, GOG and DOGOD types (D=Diphenoyl, G=Galloyl, O=Oxygen), etc. Besides their fundamental activities, e.g., reduction and anti-peroxidation properties, remarkable biological and pharmacological activities of various potencies have also been found, including, amongst others, inhibition of lipid-peroxidation, mutagenicity of carcinogens and tumor promotion, host-mediated antitumor effects specific to particular tannin structures, antiviral activity and potentiation of antibacterial activity.
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              Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver.

              Nitrosamine compounds are known hepatic carcinogens. In the metabolism of nitrosamines, such as N-nitrosodiethylamine (NDEA), there is evidence of the formation of reactive oxygen species (ROS) resulting in oxidative stress, which may be one of the factors in the etiology of cancer. The formation of ROS may alter the antioxidant system, while the presence of Vitamin E may counteract NDEA induced oxidative stress. This study was planned to determine whether pre-treatment with Vitamin E (40 mg/kg body weight, i.p., twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress in liver caused by the carcinogen. A single necrogenic dose of NDEA (200mg/kg body weight) was administered i.p. to the male albino rats with or without Vitamin E pre-treatment and the animals were sacrificed on Days 7, 14 or 21 after the administration of NDEA. The result showed enhanced levels of hepatic lipid peroxidation (LPO) and conjugated dienes of NDEA treated rats as the indices of oxidative stress, however, Vitamin E pre-treated rats administered NDEA showed decreased LPO and conjugated dienes (Day 21). Superoxide dismutase (SOD) activity in liver was not altered significantly in NDEA treated rats with or without Vitamin E pre-treatment. Catalase (CAT) activity was inhibited with NDEA treatment, however, Vitamin E pre-treatment showed recovery in hepatic CAT activity (Days 14 and 21). Total and Se-glutathione peroxidase (GSH-Px) activities and glutathione-S-transferase (GST) activity in liver increased in NDEA treated rats irrespective of Vitamin E pre-treatment. Glutathione reductase (GSH-R) activity as well as total glutathione (GSH) content in liver decreased in NDEA treated animals, both of which were recovered in Vitamin E pre-treated rats administered NDEA. Activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were increased significantly following NDEA treatment to rats with or without Vitamin E pre-treatment. The activities of AST and ALT enzymes were significantly reduced on Days 14 and 21 and ALP activity was reduced on Day 21 in NDEA+Vitamin E treated animals when compared to NDEA treated alone. LDH enzyme activity was normalized on Day 14 in Vitamin E pre-treated animals administered NDEA. However, the AST, ALT and ALP enzyme activities remained high in all treatment groups as compared to control group. Normal control and Vitamin E treated alone rats revealed normal histology of liver. On the other hand, NDEA treated animals showed alterations in normal hepatic histoarchitecture, which comprised of necrosis and vacuolization of the cells. However, the rats treated with Vitamin E+NDEA showed that the liver cells were normal, with very little necrosis (Day 21). This study concludes that the pre-treatment with Vitamin E prior to the administration of NDEA, reduced the degree of oxidative stress, although this vitamin produced only slight changes in the hepatic injury, in a time-dependent manner.
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                Author and article information

                Contributors
                Role: External Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                31 October 2014
                November 2014
                : 19
                : 11
                : 17735-17746
                Affiliations
                [1 ]Department of Pharmaceutical Sciences, Universidade Federal de Pernambuco, Recife 50740-521, Brazil
                [2 ]Department of Histology and Embriology, Universidade Federal de Pernambuco, Recife 50670-901, Brazil
                [3 ]Department of Physical Education and Sport Science, Universidade Federal de Pernambuco, Vitória de Santo Antão 55608-680, Brazil
                [4 ]Department of Nutrition, Universidade Federal de Pernambuco, Vitória de Santo Antão 55608-680, Brazil
                [5 ]Department of Physiology and Pharmacology, Universidade Federal de Pernambuco, Recife 50760-901, Brazil
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: almir.wanderley@ 123456ufpe.br ; Tel.: +41-55-819948-2243.
                Article
                molecules-19-17735
                10.3390/molecules191117735
                6270786
                25365298
                ab5692e6-97d1-4de2-ad96-70a7bbd7fe93
                © 2014 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 September 2014
                : 10 October 2014
                : 21 October 2014
                Categories
                Article

                simaroubaceae,simarouba amara,carbon tetrachloride,catechin,hepatoprotection,antioxidant

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