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      In vivo anticlastogenic effect of silymarin from milk thistle Silybum marianum L.

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          Abstract

          OBJECTIVE:

          Silymarin, extracted from the seeds of Silybum marianum L. (Milk thistle), is traditionally used for treating various illnesses such as diabetes, cancer, inflammation, hepatitis, liver cirrhosis, and renal problems. Acute cytotoxicity and genotoxicity studies have been reported with ambiguous outcomes; however, its relevant anticlastogenic potential is not yet evaluated. This study was aimed to evaluate in vivo subacute anticlastogenic properties of silymarin to validate its use as a medicinal agent.

          MATERIALS AND METHODS:

          Silymarin was isolated from seeds of milk thistle. Various genotoxicity bioassays of silymarin were performed using mice. First, the bone marrow cell proliferation was estimated by calculating mitotic index. Second, the chromosomal abnormalities in mice bone marrow cells were studied. Third, micronucleated polychromatic erythrocytes (MPE) test and in vivo activation of sister chromatid exchanges (SCEs) were carried out in mice bone marrow cells. Finally, primary spermatocytes were analyzed to estimate genotoxic effect of silymarin on germ cells.

          RESULTS:

          We found that silymarin is capable of inducing a significant increase ( P ≤ 0.05) in cell proliferation of bone marrow cells. There is no increase in chromosomal aberrations following silymarin treatments. Results clearly showed that it significantly ( P ≤ 0.05) decreased the MPE. Likewise, it was found to be a negative inducer of SCEs. It decreased in total abnormal metaphase, SCEs, MPE, and aberrant diakinesis.

          CONCLUSION:

          The results demonstrated that silymarin has a strong anticlastogenic activity upon mice genome in somatic and germ cells, indicating its safe use as a medicinal substance. Furthermore, it is not only safe but also has protective effect from clastogens.

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          Most cited references28

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          Milk thistle in liver diseases: past, present, future.

          Silybum marianum or milk thistle (MT) is the most well-researched plant in the treatment of liver disease. The active complex of MT is a lipophilic extract from the seeds of the plant and is composed of three isomer flavonolignans (silybin, silydianin, and silychristin) collectively known as silymarin. Silybin is a component with the greatest degree of biological activity and makes up 50% to 70% of silymarin. Silymarin is found in the entire plant but it is concentrated in the fruit and seeds. Silymarin acts as an antioxidant by reducing free radical production and lipid peroxidation, has antifibrotic activity and may act as a toxin blockade agent by inhibiting binding of toxins to the hepatocyte cell membrane receptors. In animals, silymarin reduces liver injury caused by acetaminophen, carbon tetrachloride, radiation, iron overload, phenylhydrazine, alcohol, cold ischaemia and Amanita phalloides. Silymarin has been used to treat alcoholic liver disease, acute and chronic viral hepatitis and toxin-induced liver diseases. Copyright © 2010 John Wiley & Sons, Ltd.
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            “Silymarin”, a Promising Pharmacological Agent for Treatment of Diseases

            Widespread use of herbal drugs because of their protective effects on different organs toxicity has been shown in many studies. These protective effects have been illustrated in the fields of nephrotoxicity, hepatotoxicity, viral hepatitis, cancer, in vitro fertilization, neurotoxicity, depression, lung diseases, prostate diseases etc. Silymarin has cytoprotection activities due to its antioxidant activity and radical scavenging. The possible known mechanisms of action of silymarin protection are blockade and adjustment of cell transporters, p-glycoprotein, estrogenic and nuclear receptors. Moreover, silymarin anti-inflammatory effects through reduction of TNF-α, protective effects on erythrocyte lysis and cisplatin-induced acute nephrotoxicity have been indicated in some studies. Silymarin has also inhibited apoptosis and follicular development in patients undergoing IVF. Basis on such data, silymarin can be served as a novel medication in complementary medicine.
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              Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

              The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Indian J Pharmacol
                Indian J Pharmacol
                IJPharm
                Indian Journal of Pharmacology
                Medknow Publications & Media Pvt Ltd (India )
                0253-7613
                1998-3751
                May-Jun 2018
                : 50
                : 3
                : 108-115
                Affiliations
                [1] Department of Medicinal Chemistry, Pharmacology and Toxicology unit, College of Clinical Pharmacy, Albaha University, Albaha, Kingdom of Saudi Arabia
                [1 ] Department of Biochemistry , Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
                [2 ] School of Pharmacy, Monash University Malaysia, Jalan lagoon selatan, Petaling Jaya, Selangor Darul Ehsan, Malaysia
                [3 ] Canadian Academy of Sciences, Toronto, Ontario M5S1Z6, Canada
                Author notes
                Address for correspondence: Dr. Sirajudheen Anwar, Department of Medicinal Chemistry, Pharmacology and Toxicology unit, College of Clinical Pharmacy, Albaha University, Albaha, Kingdom of Saudi Arabia. E-mail: clinsiraj@ 123456gmail.com
                Article
                IJPharm-50-108
                10.4103/ijp.IJP_660_16
                6106120
                30166747
                f1c5657c-d9c1-452c-ae1f-85705dc0ff14
                Copyright: © 2018 Indian Journal of Pharmacology

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 20 November 2016
                : 06 July 2018
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                bone marrow micronucleus test,clastogenic,genotoxicity,milk thistle,silybum marianum,silymarin,sister chromatid exchange

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