Blog
About

6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Campomanesia adamantium (Myrtaceae) fruits protect HEPG2 cells against carbon tetrachloride-induced toxicity

      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

          Campomanesia adamantium (Myrtaceae) is an antioxidant compounds-rich Brazilian fruit popularly known as gabiroba. In view of this, it was evaluated the hepatoprotective effects of pulp (GPE) or peel/seed (GPSE) hydroalcoholic extracts of gabiroba on injured liver-derived HepG2 cells by CCl 4 (4 mM). The results showed the presence of total phenolic in GPSE was (60%) higher when compared to GPE, associated with interesting antioxidant activity using DPPH• assay. Additionally, HPLC chromatograms and thin layer chromatography of GPE and GPSE showed the presence of flavonoids. Pretreatment of HepG2 cells with GPE or GPSE (both at 800–1000 μg/mL) significantly ( p < 0.0001) protected against cytotoxicity induced by CCl 4. Additionally, the cells treated with both extracts (both at 1000 μg/mL) showed normal morphology (general and nuclear) contrasting with apoptotic characteristics in the cells only exposed to CCl 4. In these experiments, GPSE also was more effective than GPE. In addition, CCl 4 induced a marked increase in AST ( p < 0.05) and ALT ( p < 0.0001) levels, while GPE or GPSE significantly ( p < 0.0001) reduced these levels, reaching values found in the control group. In conclusion, the results suggest that gabiroba fruits exert hepatoprotective effects on HepG2 cells against the CCl 4-induced toxicity, probably, at least in part, associated with the presence of antioxidant compounds, especially flavonoids.

          Related collections

          Most cited references 46

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

          Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model.

          The use of many halogenated alkanes such as carbon tetrachloride (CCl4), chloroform (CHCl3) or iodoform (CHI3), has been banned or severely restricted because of their distinct toxicity. Yet CCl4 continues to provide an important service today as a model substance to elucidate the mechanisms of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. In a matter of dose,exposure time, presence of potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage. CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*. This radical can bind to cellular molecules (nucleic acid, protein, lipid), impairing crucial cellular processes such as lipid metabolism, with the potential outcome of fatty degeneration (steatosis). Adduct formation between CCl3* and DNA is thought to function as initiator of hepatic cancer. This radical can also react with oxygen to form the trichloromethylperoxy radical CCl3OO*, a highly reactive species. CCl3OO* initiates the chain reaction of lipid peroxidation, which attacks and destroys polyunsaturated fatty acids, in particular those associated with phospholipids. This affects the permeabilities of mitochondrial, endoplasmic reticulum, and plasma membranes, resulting in the loss of cellular calcium sequestration and homeostasis, which can contribute heavily to subsequent cell damage. Among the degradation products of fatty acids are reactive aldehydes, especially 4-hydroxynonenal, which bind easily to functional groups of proteins and inhibit important enzyme activities. CCl4 intoxication also leads to hypomethylation of cellular components; in the case of RNA the outcome is thought to be inhibition of protein synthesis, in the case of phospholipids it plays a role in the inhibition of lipoprotein secretion. None of these processes per se is considered the ultimate cause of CCl4-induced cell death; it is by cooperation that they achieve a fatal outcome, provided the toxicant acts in a high single dose, or over longer periods of time at low doses. At the molecular level CCl4 activates tumor necrosis factor (TNF)alpha, nitric oxide (NO), and transforming growth factors (TGF)-alpha and -beta in the cell, processes that appear to direct the cell primarily toward (self-)destruction or fibrosis. TNFalpha pushes toward apoptosis, whereas the TGFs appear to direct toward fibrosis. Interleukin (IL)-6, although induced by TNFalpha, has a clearly antiapoptotic effect, and IL-10 also counteracts TNFalpha action. Thus, both interleukins have the potential to initiate recovery of the CCl4-damaged hepatocyte. Several of the above-mentioned toxication processes can be specifically interrupted with the use of antioxidants and mitogens, respectively, by restoring cellular methylation, or by preserving calcium sequestration. Chemicals that induce cytochromes that metabolize CCl4, or delay tissue regeneration when co-administered with CCl4 will potentiate its toxicity thoroughly, while appropriate CYP450 inhibitors will alleviate much of the toxicity. Oxygen partial pressure can also direct the course of CCl4 hepatotoxicity. Pressures between 5 and 35 mmHg favor lipid peroxidation, whereas absence of oxygen, as well as a partial pressure above 100 mmHg, both prevent lipid peroxidation entirely. Consequently, the location of CCl4-induced damage mirrors the oxygen gradient across the liver lobule. Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders.

            In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes, and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death. In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against cognitive decline.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A toxicologist guide to the diagnostic interpretation of hepatic biochemical parameters.

               K. Ramaiah,  S Ramaiah (2007)
              Assessing liver damage in basic toxicology research and in preclinical toxicity testing is usually evaluated by serum biochemical parameters prior to confirmation by histopathology. With the advent of newer methods such as genomics and proteomics, there is increased enthusiasm to generate "novel" predictive markers to detect liver pathology even before the alterations in clinical and histopathology parameters occur. However, serum biochemical parameters (clinical pathology) when employed accurately, can provide important and useful information in assessing not only the extent and severity of liver damage, but also the type of liver damage (membrane injury versus cholestasis and hepatic function). In order to accurately detect hepatobiliary pathologies, it is important to have a basic understanding of liver associated clinical pathology parameters with reference to their exact location, serum half-lives, tissue concentration gradient and species differences. Such understanding as discussed in this article will enable a toxicologist to identify commonly encountered toxic hepatic lesions such as necrosis, cholestasis and compromised liver function by hepatic-associated clinical pathology parameters. In addition, toxicologists will have a better grasp to effectively communicate their clinical pathology findings and interpretations to the target audiences.
                Bookmark

                Author and article information

                Contributors
                Journal
                Toxicol Rep
                Toxicol Rep
                Toxicology Reports
                Elsevier
                2214-7500
                16 December 2014
                2015
                16 December 2014
                : 2
                : 184-193
                Affiliations
                [a ]Laboratório de Nutrição Experimental, Faculdade de Nutrição, Universidade Federal de Goiás, rua 227, quadra 68, s/n, Setor Leste Universitário, 74.605-080 Goiânia, GO, Brazil
                [b ]Laboratório de Farmacologia e Toxicologia Celular – FarmaTec, Faculdade de Farmácia, Universidade Federal de Goiás, rua 240 esquina com 5ª Avenida, s/n, Setor Universitário, 74.605-220 Goiânia, GO, Brazil
                [c ]Laboratório de Pesquisa em Produtos Naturais – LPPN, Faculdade de Farmácia, Universidade Federal de Goiás, rua 240 esquina com 5ª Avenida, s/n, Setor Universitário, 74.605-220 Goiânia, GO, Brazil
                Author notes
                [* ]Corresponding author. Tel.: +55 62 3209 6044x227; fax: +55 62 3209 6044x227. marizecv@ 123456ufg.br
                [** ]Corresponding author. Tel.: +55 62 3209 6270. mmvnaves@ 123456gmail.com
                [1]

                These authors contributed equally to this work.

                Article
                S2214-7500(14)00153-X
                10.1016/j.toxrep.2014.11.018
                5598383
                © 2014 The Authors

                This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).

                Categories
                Article

                Comments

                Comment on this article

                Similar content 655

                Cited by 3

                Most referenced authors 750