22
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Hepatoprotective potential of Fagonia olivieri DC. against acetaminophen induced toxicity in rat

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Fagonia olivieri (DC) being used for the treatment of diabetes, cancer, fever and claimed to be effective in many other stress related disorders. In this study we have evaluated the F. olivieri whole methanol extract and its derived fractions for various in vitro and in vivo antioxidant studies.

          Methods

          The crude methanol extract of the whole plant of F. olivieri (FOM) and its derived fractions; n-hexane (FOH), chloroform (FOC), ethyl acetate (FOE), n-butanol (FOB) and aqueous (FOA) were evaluated for the total phenolic and flavonoid content and in vitro antioxidant abilities. The antioxidant effect of FOM was determined by acetaminophen-induced hepatotoxicity in Sprague–Dawley ( Rattus novergicus) male rats. The methanol/fractions were also analysed by HPLC analysis for the presence of polyphenolics.

          Results

          The total phenolic content of the samples ranged from 19.3 ± 0.529 to 106.2 ± 0.892 mg GAE/g extract while total flavonoid content 16.2 ± 0.881 to 50.1 ± 1.764 mg RTE/g extract, respectively. FOA showed highest radical scavenging activity for DPPH (IC 50 = 55.2 ± 1.212 μg/ml), ABTS (IC 50 = 90.2 ± 1.232 μg/ml) superoxide (IC 50 = 37.1 ± 0.643 μg/ml) and for H 2O 2 (IC 50 = 64 ± 1.463 μg/ml). FOE exhibited the highest antioxidant activities for phosphomolybdenum (IC 50 = 78.2 ± 0.883 μg/ml) and for hydroxyl radical scavenging (IC 50 = 82 ± 2.603 μg/ml). HPLC analysis of FOM and its derived fractions showed the presence of rutin, catechin and gallic acid. Elevated levels of AST, ALT, ALP, LDH and lipid profile in serum and lipid peroxidation and DNA damages in liver; while decreased activity level of CAT, SOD, GSH-Px, GR and reduced glutathione (GSH) concentration induced with acetaminophen in rat were reverted towards the control group with co-administration of FOM.

          Conclusion

          Our results showed that F. olivieri is a potential source of natural antioxidants, which justifies its use in folklore medicine.

          Related collections

          Most cited references 47

          • Record: found
          • Abstract: not found
          • Article: not found

          A modified spectrophotometric assay of superoxide dismutase.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea.

            An antioxidant fraction of Chinese green tea (green tea antioxidant; GTA), containing several catechins, has been previously shown to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. In the present study, GTA was shown to have antioxidative activity toward hydrogen peroxide (H2O2) and the superoxide radical (O2-). GTA also prevented oxygen radical and H2O2-induced cytotoxicity and inhibition of intercellular communication in cultured B6C3F1 mouse hepatocytes and human keratinocytes (NHEK cells). GTA (0.05-50 micrograms/ml) prevented the killing of hepatocytes (measured by lactate dehydrogenase release) by paraquat (1-10 mM) and glucose oxidase (0.8-40 micrograms/ml) in a concentration-dependent fashion. GTA (50 micrograms/ml) also prevented the inhibition of hepatocyte intercellular communication by paraquat (5 mM), glucose oxidase (0.8 micrograms/ml), and phenobarbital (500 micrograms/ml). In addition, GTA (50 micrograms/ml) prevented the inhibition of intercellular communication in human keratinocytes by TPA (100 ng/ml). Cytotoxicity and inhibition of intercellular communication, two possible mechanisms by which tumor promoters may produce their promoting effects were therefore prevented by GTA. The inhibition of these two effects of pro-oxidant compounds may suggest a mechanism by which GTA inhibits tumor promotion in vivo.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Acetaminophen-induced hepatotoxicity.

              The analgesic acetaminophen causes a potentially fatal, hepatic centrilobular necrosis when taken in overdose. The initial phases of toxicity were described in Dr. Gillette's laboratory in the 1970s. These findings indicated that acetaminophen was metabolically activated by cytochrome P450 enzymes to a reactive metabolite that depleted glutathione (GSH) and covalently bound to protein. It was shown that repletion of GSH prevented the toxicity. This finding led to the development of the currently used antidote N-acetylcysteine. The reactive metabolite was subsequently identified to be N-acetyl-p-benzoquinone imine (NAPQI). Although covalent binding has been shown to be an excellent correlate of toxicity, a number of other events have been shown to occur and are likely important in the initiation and repair of toxicity. Recent data have shown that nitrated tyrosine residues as well as acetaminophen adducts occur in the necrotic cells following toxic doses of acetaminophen. Nitrotyrosine was postulated to be mediated by peroxynitrite, a reactive nitrogen species formed by the very rapid reaction of superoxide and nitric oxide (NO). Peroxynitrite is normally detoxified by GSH, which is depleted in acetaminophen toxicity. NO synthesis (serum nitrate plus nitrite) was dramatically increased following acetaminophen. In inducible nitric oxide synthase (iNOS) knockout mice, acetaminophen did not increase NO synthesis or tyrosine nitration; however, histological evidence indicated no difference in toxicity. Acetaminophen did not cause hepatic lipid peroxidation in wild-type mice but did cause lipid peroxidation in iNOS knockout mice. These data suggest that NO may play a role in controlling lipid peroxidation and that reactive nitrogen/oxygen species may be important in toxicity. The source of the superoxide has not been identified, but our recent finding that NADPH oxidase knockout mice were equally sensitive to acetaminophen and had equal nitration of tyrosine suggests that the superoxide is not from the activation of Kupffer cells. It was postulated that NAPQI-mediated mitochondrial injury may be the source of the superoxide. In addition, the significance of cytokines and chemokines in the development of toxicity and repair processes has been demonstrated by several recent studies. IL-1beta is increased early in acetaminophen toxicity and may be important in iNOS induction. Other cytokines, such as IL-10, macrophage inhibitory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1), appear to be involved in hepatocyte repair and the regulation of proinflammatory cytokines.
                Bookmark

                Author and article information

                Contributors
                umbreen.rashid@gmail.com
                mrkhanqau@yahoo.com
                moniba_qau@yahoo.com
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                9 November 2016
                9 November 2016
                2016
                : 16
                Affiliations
                [1 ]Department of Environmental Sciences, GC Women University Sialkot, Sialkot, Pakistan
                [2 ]Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320 Pakistan
                Article
                1445
                10.1186/s12906-016-1445-x
                5103455
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

                Comments

                Comment on this article