Biomedicine & Preventive Nutrition 2 (2012) 9–15 Available online at www.sciencedirect.com Original article Attenuation of mitochondrial oxidative stress by morin during chemical carcinogen-mediated mammary carcinogenesis Nandhakumar Ramadass , Salini Kombiyil , Nirmal Kumar Kasinathan , Niranjali Devaraj Sivasithamparam ∗ Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India a r t i c l e i n f o Article history: Received 30 September 2011 Accepted 4 November 2011 Keywords: Mammary cancer Citric acid cycle enzymes Respiratory chain enzymes a b s t r a c t In this study we evaluated the effects of morin on the mitochondrial functions with reference to mito- chondrial citric acid cycle enzymes, respiratory chain complex enzymes, membrane bound ATPases and protein-bound carbohydrates in mammary tissues of 7,12-dimethyl benz(a)-anthracene (DMBA)- induced mammary carcinoma of Sprague-Dawley rats. Adult female Sprague-Dawley rats were induced mammary carcinoma by administration of DMBA (25 mg/kg b.wt.) orally. The normal and cancer-induced rats were treated with morin (50 mg/kg b.wt.) for three times per week for 13 weeks. Cancer-induced rats showed a significantly increased level of lipid peroxidation (LPO) products and protein-bound carbohy- drates with concomitant decreased levels of nonenzymic antioxidants (vitamin C, reduced glutathione [GSH]) and vitamin E and enzymic antioxidants (superoxide dismutase [SOD]), catalase (CAT) and glu- tathione peroxidase (GPx) in the mammary tissue. Decreased levels of ATPases, citric acid cycle enzymes and respiratory chain enzymes were observed in the mammary tissue of tumor bearing group of rats. Treatment with morin brought back lipid peroxidation products, nonenzymic and enzymic antioxidants to near normalcy. Since morin treatment decreases lipid peroxidation and enhances antioxidants and enzymes involved in the biochemical pathways, it may play a critical role in oxidative stress-related changes in cancer-induced rats and may possess a potent antioxidant potential to protect subcellular organelles being damaged by oxidative stress. © 2011 Elsevier Masson SAS. All rights reserved. 1. Introduction Management of cancer is directed towards the development of naturally occurring compounds for chemotherapeutics [1]. An anticancer drug should exterminate or incapacitate cancer cells without damaging normal cells. It is vital to develop chemopreven- tive strategies to prevent the severity and magnitude of the cancer by exploiting pharmacological or natural agents to obstruct initia- tion or to arrest progression in premalignant cells. Fruits, vegetables and plant-derived beverages such as grape-fruit juice, tea and red wine possess the most abundant polyphenolic compounds called flavonoids [2], which claims to be a pharmaco-intrusion in the pre- vention of a variety of diseases, including allergies, cardiovascular disease, certain forms of cancer, hepatic diseases, and inflammation [3]. Morin (3,5,7,20,40-pentahydroxyflavone), a member of flavonols, is a yellowish pigment found in almond [4], red wine [5], the old fustic (Chlorophora tinctoria) and osage ∗ Corresponding author. Tel.: +91 44 22351269 ext 231; fax: +91 44 22352494. E-mail address: niranjali@yahoo.com (N.D. Sivasithamparam). orange (Maclura pomifera) as well as in many Chinese herbs [6]. Morin displays a variety of biological actions such as anti- allergic, anti-inflammatory, antiperoxidative, anti-mutagenic and anti-carcinogenic effects [7–11]. Frequent production of free radicals and non-radical oxidiz- ing species in animals treated with carcinogens cause free radicals and electrophiles mediated oxidative stress favoring the progres- sion of carcinogenesis and tumorogenesis. These highly reactive species (ROS) causes oxidative modification of DNA, proteins, lipids and small intracellular molecules [12]. Membrane phospholipids peroxidation causes loss of lipid milieu and structural as well as functional integrity of cell membrane bound enzymes. Mito- chondria are an important cellular source of oxygen radical which represents a preferred intracellular target for free radical attack [13]. Thus, the study of mitochondrial status and functions during carcinoma is of particular interest. Glycoconjugates are major components of cellular membranes which are ubiquitous in mammalian cells. Glycopeptides having diverse immunological properties are present in the plasma mem- brane of erythrocytes and fibroblasts and plays a major role in cell-to-cell contact, growth regulation and acts as a binding site for hormones [14]. Due to the increased activity of glycosyltransferases 2210-5239/$ – see front matter © 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.bionut.2011.11.004