Coenzyme Q 9 Provides Cardioprotection after Converting into Coenzyme Q 10 ISTVAN LEKLI, †,‡ SOMAK DAS, † SAMARJIT DAS, † SUBHENDU MUKHERJEE, † ISTVAN BAK, ‡ BELA JUHASZ, ‡ DEBASIS BAGCHI, § GOLAKOTI TRIMURTULU, | A. V. KRISHNARAJU, | KRISHANU SENGUPTA, | ARPAD TOSAKI, †,‡ AND DIPAK K. DAS* ,†,§ Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut, Department of Pharmacy, University of Debrecen, Debrecen, Hungary, InterHealth Nutraceuticals, Benicia, California, and Laila Impex R & D Center, Vijayawada, Andhra Pradesh, India Coenzyme Q 10 (CoQ 10 ) has been extensively studied as adjunctive therapy for ischemic heart disease, and its cardioprotective ability is well-established. The mitochondrial respiratory chain contains several coenzymes, including CoQ 1 , CoQ 2 , CoQ 4 , CoQ 6 , CoQ 7 , CoQ 8 , CoQ 9 , and CoQ 10 . It is not known whether other CoQs, especially CoQ 9 , is equally cardioprotective as CoQ 10 . The present study was designed to determine if CoQ 9 could protect guinea pig hearts from ischemia reperfusion injury. Guinea pigs were randomly divided into three groups: groups I and II were fed CoQ 9 and CoQ 10 , respectively, for 30 days while group III served as control. After 30 days, the guinea pigs were sacrificed and isolated hearts were perfused via working mode were subjected to 30 min ischemia followed by 2 h of reperfusion. Cardioprotection was assessed by evaluating left ventricular function, ventricular arrhythmias, myocardial infarct size, and cardiomyocyte apoptosis. Samples of hearts were examined for the presence of CoQ 9 and CoQ 10 . The results demonstrated that both CoQ 9 and CoQ 10 were equally cardioprotective, as evidenced by their abilities to improve left ventricular performance and to reduce myocardial infarct size and cardiomyocyte apoptosis. High performance liquid chromato- graphic (HPLC) analysis revealed that a substantial portion of CoQ 9 had been converted into CoQ 10 . The results indicate that CoQ 9 by itself, or after being converted into CoQ 10 , reduced myocardial ischemia/reperfusion-induced injury. KEYWORDS: Coenzyme Q 9 ; coenzyme Q 10 ; heart; ischemic reperfusion injury INTRODUCTION Coenzyme Q 10 (CoQ 10 ), a member of the ubiquinone family, is an essential component of the mitochondrial electron transfer chain, which is required for ATP synthesis and functions as an antioxidant in cell membranes and lipoproteins (1). CoQ 10 is also a powerful antioxidant not only within the mitochondria but also in other organelle membranes containing CoQ (2). CoQ 10 is ubiquitously present in the mammalian tissues, especially in the heart. The fact that the levels of endogenous CoQ 10 in the heart decreases during ischemic heart disease including heart failure prompted clinical trials with CoQ 10 in patients that suffered from heart failure (3). Randomized, double- blind, placebo-controlled trials of oral administration of CoQ 10 have confirmed the effectiveness of CoQ 10 in improving angina episodes, arrhythmias, and left ventricular function in patients with acute myocardial infarction (4). CoQ 9 is found in rodents like mice and rats, while CoQ 6 , CoQ 7 , and CoQ 8 are found in yeast and bacteria (5, 6). The majority of CoQ 9 in rat liver is present in its reduced form (ubiquinol), which exerts its antioxidative function (7). Similar to CoQ 10 , CoQ 9 is not merely a compound responsible for energy transduction in mitochondrial membrane in rat heart; it also serves as a functional element in the cells and possesses ability for redox cycling. CoQ 9 differs from CoQ 10 with respect to the number of isoprenoid units in the tail: CoQ 9 has nine units in contrast to the presence of 10 units in CoQ 10 . Most of the CoQ 10 is found in mammalian hearts including human myocardium (7). CoQ 10 is not an essential nutrient, because it can be synthesized in the body. High amounts of CoQ 10 can also be found in several food products, including meat, fish, peanuts, and broccoli (8). Dietary intake of CoQ 10 is about 2-5 mg per day, which is inadequate for the body under physiological conditions (2). * Corresponding author. Tel: (860) 679-3687. Fax: (860) 679-4606. E-mail: DDAS@NEURON.UCHC.EDU. † University of Connecticut School of Medicine. ‡ University of Debrecen. § InterHealth Nutraceuticals. | Laila Impex R & D Center. J. Agric. Food Chem. 2008, 56, 5331–5337 5331 10.1021/jf800035f CCC: $40.75  2008 American Chemical Society Published on Web 06/11/2008