JOURNAL OF MEDICINAL FOOD J Med Food 11 (4) 2008, 733–740 © Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition DOI: 10.1089/jmf.2007.0130 Terminalia arjuna Protects Mouse Hearts Against Sodium Fluoride-Induced Oxidative Stress Mahua Sinha,* Prasenjit Manna,* and Parames C. Sil Department of Chemistry, Bose Institute, Kolkata, India ABSTRACT Fluoride is a ubiquitous environmental pollutant. In the current study we have investigated the antioxidative properties of an ethanol extract of the bark of Terminalia arjuna (T. arjuna ethanol extract [TAEE]) against sodium fluoride (NaF)-induced oxidative stress in murine heart. Experimental mice were divided into four groups. The first group served as the normal control. The second group received NaF at a dose of 600 ppm through drinking water for 1 week and served as the toxin control. The third group was exposed to TAEE (at a dose of 50 mg/kg of body weight for 1 week) prior to NaF in- toxication, and the last group was treated with vitamin C at a dose of 100 mg/kg body weight for 1 week prior to NaF in- toxication and served as the positive control in the study. The activities of various antioxidant enzymes (superoxide dismu- tase, catalase, and glutathione S-transferase), levels of cellular metabolites, reduced glutathione, and oxidized glutathione, levels of lipid peroxidation end products, and protein carbonyl contents were determined in the cardiac tissues of all the ex- perimental animals. NaF intoxication significantly altered all the indices related to the prooxidant–antioxidant status of the heart; treatment with the active constituents prior to NaF administration, however, prevented these alterations. In addition, the ferric reducing/antioxidant power assay revealed that TAEE enhanced the cardiac intracellular antioxidant activity. Histolog- ical studies also demonstrated a cardioprotective action of TAEE. The combined results suggest that TAEE protects murine hearts from NaF-induced oxidative stress, probably via its antioxidant properties. KEY WORDS: • antioxidant • cardiac oxidative stress • cardiac protection • reactive oxygen species • sodium fluoride • Terminalia arjuna 733 INTRODUCTION H ERBAL MEDICINE (PHYTOTHERAPY) is the oldest form of medicine known to mankind. It uses specific medicinal plants or their products for the healing properties that pro- mote health and body resistance to disease. Medicinal uses of many plants have been reported in the literature. Termi- nalia arjuna, belonging to the family Combretaceae, has held a reputed position in Ayurvedic medicine since ancient times. 1 It is used as a functional ingredient in water and other beverages to maintain good health. 2,3 Experimental and clin- ical studies have confirmed the beneficial effects of this plant in human pathophysiology. 4,5 Satyanarayana et al. 6 re- ported that chronic administration of a 70% alcoholic ex- tract of the bark of T. arjuna reduced the platelet count in dogs. A dose-dependent decrease in heart pulse rate and blood pressure was noted in dogs given an alcoholic extract of T. arjuna bark extract intravenously. 7 The herbal formu- lation of T. arjuna can also be used in the treatment of hy- percholesterolemia. 8 A previous experiment in our labora- tory showed that the aqueous extract of T. arjuna bark is protective against carbon tetrachloride- and sodium fluoride (NaF)-induced hepato- and nephrotoxicities. 9,10 Fluoride in varying concentration induces various health problems in people and in animals living in the area of en- demic fluorosis. 11 It has been found that about 62 million people in India in 17 states are affected with dental, skele- tal, and nonskeletal fluorosis. 12 In addition to dental and skeletal problems, fluorosis can adversely affect tissues and organs as exhibited by pathological changes. 13,14 Knowl- edge on the toxic effects of fluoride on heart is limited. 15,16 Shashi and Thapar 17 reported that chronic and acute fluo- ride intoxication caused myocardial damage in albino rab- bits. The present study was undertaken to assess the cardio- protective effect of T. arjuna ethanol extract (TAEE) against NaF-induced cardiac disorders. In vitro antioxidant power of TAEE was measured by the ferric reducing/antioxidant power (FRAP) assay. The extent of cardiac damage and the protective effect of TAEE were evaluated by measuring (1) the extent of lipid peroxidation, (2) the activities of the an- tioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), (3) the levels of cellular metabolites, reduced glutathione (GSH), and ox- Manuscript received 13 June 2007. Revision accepted 13 September 2007. Address reprint requests to: Dr. Parames C. Sil, Reader, Department of Chemistry, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata-700009, West Bengal, India, E- mail: parames@bosemain.boseinst.ac.in or parames_95@yahoo.co.in *Both of these authors contributed equally to the study.