Original Article POTENTIAL GENOTOXICITY AND HISTOPATHOLOGICAL ALTERATION EVALUATION OF HEPTEX® EL-MAKAWY I. AIDA 1* ABDEL-NAIM B. ASHRAF 2 BARAKAT ALAA 3 , , 1 Cell Biology Department, National Research Centre, 33 El Bohouth St. Dokki, Giza, Egypt-P O.12622. 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt, 3 Biochemistry and Biotechnology Department, Family of Pharmacy, Heliopolis University, Cairo, Egypt Email: aelmakawy@yahoo.com Received: 02 Apr 2015 Revised and Accepted: 30 May 2015 ABSTRACT Objective: The present study was performed in order to evaluate potential genotoxicity and the histopathological alteration of a traditional herbal prescription Heptex that used in the treatment of liver disease. Methods: The genotoxicity were evaluated using the in vivo chromosome aberration and micronucleus assays in bone marrow cells of male and female Sprague-Dawley rats. In addition, in vitro chromosome aberration assay in Chinese hamster ovary (CHO) cells and bacterial reverse mutations assay in Salmonella typhimurium strains and Escherichia coli (WP2-uvrA/) with and without metabolic activation system (S9 mix) were performed. Histopathological study was conducted in liver, ovary and testis tissue of Sprague-Dawley rats. Results: The genotoxicity assessment showed that Heptex did not significantly increase the number of chromosomal aberrations and frequencies of micro nucleated polychromatic erythrocytes in bone marrow cells of both male and female rats. In addition, there were no increases in the number of revertant colonies at any concentrations of Heptex used in the study. Heptex did not produce any structural aberration in CHO cells in the presence or absence of S9 mix. In addition, there were no histopathological changes induced by Heptex in rat liver, ovary and testis. Conclusion: Based on abovementioned findings, we can conclude that Heptex is generally non-toxic and does not exhibit genotoxicity or histopathological alteration. Keywords: Heptex, Genotoxicity, In vivo, In vitro, Chromosome aberrations, Micronucleus, Bacterial reverse mutation, Histopathology. INTRODUCTION Heptex® capsule consists of Dukong Anak powdered extract from aerial parts of Phyllanthus niruri and Milk thistle powdered extract from fruits of Silybum marianum (L.) and function as liver tonic and Hepatitis. for beneficial Phyllanthus niruri genus (Heptex, popular most one of the is Phyllanthaceae) Phyllanthus, family tropical and subtropical herbal plants [1]. Phyllanthus niruri is a well-known plant in Malaysian traditional medicine, locally known as Dukung anak that means carry baby; because the plants carry the fruits on their backs and underneath the feathered-like leaves [2, 3] The phytochemical compounds of many of Phyllanthus species such as tannins, ellagitannins flavonoids have been isolated and characterized [2, 4, 5]. Several studies have shown antioxidants activity of various Phyllanthus species using different solvents and methods of extractions [4, 6, 7]. The potential pharmacological effects of the many of these isolated compounds have been assessing [8, 9]. The plants of genus Phyllanthus have long been used to treat liver diseases [10]. In fact, a wide number of experimental studies have demonstrated the hepato protective potential of Phyllanthus plants in vitro and in vivo systems [11-14]. Phyllanthus niruri have been report to have hepato protective activity [7, 15], antioxidant [16] and lipid lowering activity [17]. Its actions were evaluated on various organs including liver, kidneys and testes [18]. Silymarin, an extract from the milk thistle fruit (Silybum marianum, Family Asteraceae) has been utilized for remedy of liver diseases such as sirrhosis or hepatitis for many years [19-21]. Silymarin is a mixture of flavonoids and polyphenols and it is contained several different flavonoids, like silibinin, isosilibinin, silichristin and silidianin. Silibinin is the major bioactive component of this material [22]. Silymarin has membrane-stabilizing and antioxidant activity, it promotes hepatocyte regeneration, reduces an inflammatory reaction, and inhibits fibrogenesis [23]. The pharmacological data show that Silymarin possesses fairly specific effects on cell- regulating mechanisms, beyond the well known reactive oxygen species (ROS) scavenging properties confirmed in new studies indicating a potential to reduce toxic effects of other drugs [24]. Herbal medicines are very popular in developing and underdeveloped countries. Reports indicate that the ideal herbal drugs are very safe and free from side effect is false [25]. Therefore, clear understanding of potential adverse effect of herbs used by the human population is necessary for implementing safety measures to the public. There is paucity of evidence from literature on possible genotoxicity of Phyllanthus niruri extract. Therefore, the aim of this study was to determine the genotoxicity and histopathological changes of Heptex in Sprague-Dawley rats. The in vivo genotoxicity study was conducted by using chromosome aberration assay and micronucleus test. The in vitro genotoxicity study was conduct using the chromosome aberration assay in Chinese hamster ovary cells and the bacterial reverse mutation assay. In addition, histopathological study was conducted on the liver, ovary and testis of Sprague-Dawley rats. MATERIALS AND METHODS Drug Heptex® hard gelatin vegetable origin capsule consist of 200 mg Dukong Anak powdered extract from aerial parts of Phyllanthus niruri and 100 mg Milk thistle powdered Extract from fruits of Silybum marianum (L.) as active ingredients. 100 mg of starch 1500 (inactive ingredient) was used as diluents. The extracts were obtained from TPM Biotech Sdn Bhd, Kuala Lumpur, Malaysia. Animals Fifty Sprague-Dawley male and female rats (25♀, 25♂) with a body weight ranging from 120 to 150 g for both sexes were obtained from Misr University for Science and Technology, 6 th of October, Egypt. The animals were acclimated for a period of one week before the beginning of the experiments. Rats were maintained under controlled of temperature (22±3 °C), 50-55% relative humidity and International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 7, 2015 Innovare Academic Sciences