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      Caffeic acid improves cell viability and protects against DNA damage: involvement of reactive oxygen species and extracellular signal-regulated kinase

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          Abstract

          Hormesis is an adaptive response to a variety of oxidative stresses that renders cells resistant to harmful doses of stressing agents. Caffeic acid (CaA) is an important antioxidant that has protective effects against DNA damage caused by reactive oxygen species (ROS). However, whether CaA-induced protection is a hormetic effect remains unknown, as is the molecular mechanism that is involved. We found that a low concentration (10 μM) of CaA increased human liver L-02 cell viability, attenuated hydrogen peroxide (H 2O 2)-mediated decreases in cell viability, and decreased the extent of H 2O 2-induced DNA double-strand breaks (DSBs). In L-02 cells exposed to H 2O 2, CaA treatment reduced ROS levels, which might have played a protective role. CaA also activated the extracellular signal-regulated kinase (ERK) signal pathway in a time-dependent manner. Inhibition of ERK by its inhibitor U0126 or by its specific small interfering RNA (siRNA) blocked the CaA-induced improvement in cell viability and the protective effects against H 2O 2-mediated DNA damage. This study adds to the understanding of the antioxidant effects of CaA by identifying a novel molecular mechanism of enhanced cell viability and protection against DNA damage.

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          Most cited references 38

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          Exercise, oxidative stress and hormesis.

          Physical inactivity leads to increased incidence of a variety of diseases and it can be regarded as one of the end points of the exercise-associated hormesis curve. On the other hand, regular exercise, with moderate intensity and duration, has a wide range of beneficial effects on the body including the fact that it improves cardio-vascular function, partly by a nitric oxide-mediated adaptation, and may reduce the incidence of Alzheimer's disease by enhanced concentration of neurotrophins and by the modulation of redox homeostasis. Mechanical damage-mediated adaptation results in increased muscle mass and increased resistance to stressors. Physical inactivity or strenuous exercise bouts increase the risk of infection, while moderate exercise up-regulates the immune system. Single bouts of exercise increases, and regular exercise decreases the oxidative challenge to the body, whereas excessive exercise and overtraining lead to damaging oxidative stress and thus are an indication of the other end point of the hormetic response. Based upon the genetic setup, regular moderate physical exercise/activity provides systemic beneficial effects, including improved physiological function, decreased incidence of disease and a higher quality of life.
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            Exercise and hormesis: oxidative stress-related adaptation for successful aging.

            The hormesis theory purports that biological systems respond with a bell-shaped curve to exposure to chemicals, toxins, and radiation. Here we extend the hormesis theory to include reactive oxygen species (ROS). We further suggest that the beneficial effects of regular exercise are partly based on the ROS generating capability of exercise, which is in the stimulation range of ROS production. Therefore, we suggest that exercise-induced ROS production plays a role in the induction of antioxidants, DNA repair and protein degrading enzymes, resulting in decreases in the incidence of oxidative stress-related diseases and retardation of the aging process.
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              Chlorogenic Acid and Caffeic Acid Are Absorbed in Humans

              Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the absorption of chlorogenic acid and caffeic acid in humans are lacking. We determined the absorption of chlorogenic acid and caffeic acid in a cross-over study with 4 female and 3 male healthy ileostomy subjects. In such subjects, degradation by the colonic microflora is minimal and absorption can be calculated as the amount ingested minus the amount excreted in ileostomy effluent. The ileostomy subjects ingested 2.8 mmol chlorogenic acid and 2.8 mmol caffeic acid on separate days in random order and subsequently collected ileostomy fluid and urine for 24 h. Absorption of chlorogenic acid was 33 +/- 17% (mean +/- SD) and of caffeic acid 95 +/- 4%. Traces of the ingested chlorogenic acid and 11% of the ingested caffeic acid were excreted in urine. Thus, one third of chlorogenic acid and almost all of the caffeic acid were absorbed in the small intestine of humans. This implies that part of chlorogenic acid from foods will enter into the blood circulation, but most will reach the colon.
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                Author and article information

                Journal
                Braz J Med Biol Res
                Braz. J. Med. Biol. Res
                Brazilian Journal of Medical and Biological Research
                Associação Brasileira de Divulgação Científica
                0100-879X
                1414-431X
                27 March 2015
                June 2015
                : 48
                : 6
                : 502-508
                Affiliations
                [1 ]Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, China
                [2 ]Department of Hygiene Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing, China
                [3 ]The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
                Author notes
                Correspondence: Lei Li, E-mail: <drleili@ 123456hotmail.com>
                [*]

                These authors contributed equally to this study.

                Article
                10.1590/1414-431X20143729
                4470308
                25831202
                56136cad-3cf0-4932-9013-33b5bf07a784

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 7, Tables: 0, References: 33, Pages: 7
                Funding
                Funded by: the Natural Science Foundations of China
                Award ID: #81072338, #81473020, and #81402667
                Funded by: the Priority Academic Program Development of Jiangsu Higher Education Institutions (2010), and a Technology Development Fund of Nanjing Medical University
                Award ID: #2013NJMU021
                Categories
                Biomedical Sciences

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