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      Farnesol Protects Against Intratracheally Instilled Cigarette Smoke Extract-Induced Histological Alterations and Oxidative Stress in Prostate of Wistar Rats

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          Abstract

          Background:

          In the present study, cigarette smoke contains more than four thousand chemicals, many of which are known to be carcinogen or cancer promoter. Many epidemiological reports suggest that cigarette smokers are at a greater risk of other cancers such as oropharynx, stomach, pancreas, liver, kidney, urinary bladder, colon, and breast, however, the few epidemiological reports are available on the role of cigarette smoke in the development of prostate cancer. In this study, we investigated the effects of farnesol against cigarette smoke extract (CSE)-induced oxidative stress in prostate.

          Materials and Methods:

          Farnesol was administered by gavage (50 mg/kg and 100 mg/kg b.wt. in corn oil) one time daily for 7 days. On day 7, rats were exposed to cigarette smoke via intratracheal instillation of aqueous CSE. CSE enhanced prostatic xanthine oxidase activity and lipid peroxidation (LPO) along with decrease in prostatic glutathione content, antioxidant enzymes activities, viz., glutathione peroxidase, glutathione reductase, and catalase.

          Results:

          Pre-treatment of rats with farnesol (50 mg/kg and 100 mg/kg b.wt. orally) resulted in significant decreased in xanthine oxidase activity and LPO at both the doses. The level of reduced glutathione, the activities of glutathione dependent enzymes and antioxidant enzymes were also augmented to significant level with pre-treatment with farnesol.

          Conclusion:

          Thus, our data suggests that farnesol is a potent defense against CSE induced prostatic oxidative damage in rodent model of experiment.

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          Most cited references38

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          Free-radical chemistry of cigarette smoke and its toxicological implications.

          Cigarette smoke contains two very different populations of free radicals, one in the tar and one in the gas phase. The tar phase contains several relatively stable free radicals; we have identified the principal radical as a quinone/hydroquinone (Q/QH2) complex held in the tarry matrix. We suggest that this Q/QH2 polymer is an active redox system that is capable of reducing molecular oxygen to produce superoxide, eventually leading to hydrogen peroxide and hydroxyl radicals. In addition, we have shown that the principal radical in tar reacts with DNA in vitro, possibly by covalent binding. The gas phase of cigarette smoke contains small oxygen- and carbon-centered radicals that are much more reactive than are the tar-phase radicals. These gas-phase radicals do not arise in the flame, but rather are produced in a steady state by the oxidation of NO to NO2, which then reacts with reactive species in smoke such as isoprene. We suggest that these radicals and the metastable products derived from these radical reactions may be responsible for the inactivation of alpha 1-proteinase inhibitor by fresh smoke. Cigarette smoke oxidizes thiols to disulfides; we suggest the active oxidants are NO and NO2. The effects of smoke on lipid peroxidation are complex, and this is discussed. We also discuss the toxicological implications for the radicals in smoke in terms of a number of radical-mediated disease processes, including emphysema and cancer.
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            Tomato lycopene and its role in human health and chronic diseases.

            Lycopene is a carotenoid that is present in tomatoes, processed tomato products and other fruits. It is one of the most potent antioxidants among dietary carotenoids. Dietary intake of tomatoes and tomato products containing lycopene has been shown to be associated with a decreased risk of chronic diseases, such as cancer and cardiovascular disease. Serum and tissue lycopene levels have been found to be inversely related to the incidence of several types of cancer, including breast cancer and prostate cancer. Although the antioxidant properties of lycopene are thought to be primarily responsible for its beneficial effects, evidence is accumulating to suggest that other mechanisms may also be involved. In this article we outline the possible mechanisms of action of lycopene and review the current understanding of its role in human health and disease prevention.
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              Prevention and therapy of cancer by dietary monoterpenes.

              Monoterpenes are nonnutritive dietary components found in the essential oils of citrus fruits and other plants. A number of these dietary monoterpenes have antitumor activity. For example, d-limonene, which comprises >90% of orange peel oil, has chemopreventive activity against rodent mammary, skin, liver, lung and forestomach cancers. Similarly, other dietary monoterpenes have chemopreventive activity against rat mammary, lung and forestomach cancers when fed during the initiation phase. In addition, perillyl alcohol has promotion phase chemopreventive activity against rat liver cancer, and geraniol has in vivo antitumor activity against murine leukemia cells. Perillyl alcohol and d-limonene also have chemotherapeutic activity against rodent mammary and pancreatic tumors. As a result, their cancer chemotherapeutic activities are under evaluation in Phase I clinical trials. Several mechanisms of action may account for the antitumor activities of monoterpenes. The blocking chemopreventive effects of limonene and other monoterpenes during the initiation phase of mammary carcinogenesis are likely due to the induction of Phase II carcinogen-metabolizing enzymes, resulting in carcinogen detoxification. The post-initiation phase, tumor suppressive chemopreventive activity of monoterpenes may be due to the induction of apoptosis and/or to inhibition of the post-translational isoprenylation of cell growth-regulating proteins. Chemotherapy of chemically induced mammary tumors with monoterpenes results in tumor redifferentiation concomitant with increased expression of the mannose-6-phosphate/insulin-like growth factor II receptor and transforming growth factor beta1. Thus, monoterpenes would appear to act through multiple mechanisms in the chemoprevention and chemotherapy of cancer.
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                Author and article information

                Journal
                Toxicol Int
                Toxicol Int
                TI
                Toxicology International
                Medknow Publications & Media Pvt Ltd (India )
                0971-6580
                0976-5131
                Jan-Apr 2013
                : 20
                : 1
                : 35-42
                Affiliations
                [1]Departments of Medical Elementology and Toxicology, Molecular Carcinogenesis and Chemoprevention Division, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India
                Author notes
                Address for correspondence: Dr. Sarwat Sultana, Department of Medical Elementology and Toxicology, Faculty of Science, Molecular Carcinogenesis and Chemoprevention Division, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi - 110 062, India. E-mail: sarwat786@ 123456rediffmail.com
                Article
                TI-20-35
                10.4103/0971-6580.111563
                3702125
                23833436
                eb87a7e3-e49c-49cf-ac0c-d0ebe20d62b4
                Copyright: © Toxicology International

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Original Article

                Toxicology
                cigarette smoke extract,farnesol,intratracheal instillation,prostate,testis
                Toxicology
                cigarette smoke extract, farnesol, intratracheal instillation, prostate, testis

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