International Journal of Clinical Toxicology, 2013, 1, 9-17 9 E-ISSN: 2310-4007/13 © 2013 Pharma Professional Services Amelioration of Cyclophosphamide-Induced Hepatotoxicity by the Brown Seaweed Turbenaria ornata Ayman M. Mahmoud 1,* , Omnia E. Hussein 1 and Shymaa A. Ramadan 2 1 Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Egypt 2 Physiology Department, Faculty of Medicine, Beni-Suef University, Egypt Abstract: The present study was designed to investigate the possible protective effects of the brown seaweed, Turbenaria ornata, against cyclophosphamide (CP)-induced hepatotoxicity in rats. The biochemical results showed that administration of CP induced hepatic damage associated with a significant increase in the serum marker enzymes aspartate and alanine transaminases (AST, ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). In addition, CP induced oxidative stress in the liver as evident from the increased lipid peroxidation (LPO), declined glutathione (GSH) content and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. Moreover, administration of CP was associated with a significant decrease in serum adiponectin level and an increase in serum tumor necrosis factor alpha (TNF-). Concomitant administration of Turbenaria ornata extract efficiently alleviated the altered biochemical parameters. In conclusion, Turbenaria ornata extract showed a marked hepatoprotective effect against CP-induced hepatotoxicity through alleviation of the declined serum adiponectin in addition to its antioxidant and anti-inflammatory efficacies. Keywords: Cyclophosphamide, hepatotoxicity, adiponectin, oxidative stress, Seaweeds. 1. INTRODUCTION Cyclophosphamide (CP), a nitrogen mustard alkylating agent, is widely used in the treatment of variety of human malignancies and disorders like breast cancer, carcinoma of the lung [1], systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis [2,3]. However, use of CP is often restricted because of its wide adverse side effects and toxicity that includes nausea, vomiting, alopaecia, mucosal ulceration, pulmonary fibrosis, hemopoetic suppression, nephrotoxicity, urotoxicity, cardiotoxicity and hepatic toxicity [4-7]. Biotransformation of CP mediates through involvement of cyt p450 mixed function oxidases with the formation of metabolites phosphoramide mustard and acrolein which are highly toxic [8,9]. Through this pathway, CP has potential to generate superfluous reactive oxygen species (ROS) [10,11]. In addition, experimental evidence suggests that oxidative stress is responsible for CP hepatotoxicity [12-14]. Adiponectin is a protein produced and secreted almost exclusively by adipocytes [15]. First described over a decade ago, the interest in the biology of adiponectin was spurred by the discovery of measurable concentrations in plasma, its structural resemblance to complement factor C1q and the consistent finding of decreased levels in obesity [16]. *Address correspondence to this author at the Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, 62511, Beni-Suef, Egypt; Tel: +2-011-44168280; E-mails: aymano911@yahoo.com, ayman.mahmoud@science.bsu.edu.eg In humans, adiponectin is an insulin-sensitizing, vascular-protective, anti-inflammatory protein [17,18] associated with a more favourable lipoprotein subclass profile [19]. To date, most of our understanding of adiponectin has been in its association with metabolic and cardiovascular health. Hypoadiponectinaemia is associated with obesity, insulin resistance and type 2 diabetes [18], as well as atherosclerosis, hypertension and coronary artery disease [20]. The hepatoprotective and antifibrogenic effects of adiponectin have been demonstrated in animal models by numerous pharmacological, genetic, gain- and loss-of-function studies [21,22]. Over the past several decades, seaweeds have been reported to possess biological activity of potential medicinal value [23]. It was reported that seaweeds are rich source of bioactive compounds, such as terpenoids, phlorotanins, fucoidans, sterols and glycolipids, and the extracts or isolated pure components from seaweeds posses a wide range of pharmacological properties such as anticancer, antibacterial, antifungal, anti-viral, anti-inflammatory, anticoagulant, antioxidant, hypoglycaemic, hypolipi- demic, antimelanogenic, anti-bone loss, hepatopro- tective and neuroprotective activities [24,25]. Earlier reports indicated that the extracts of brown seaweeds belonging to Turbinaria spp. were found to have antioxidant and anti-inflammatory activities [26,27]. Reports regarding the protective effect and clinical significance of brown algae against CP-induced hepatotoxicity in rats are scanty in scientific literature.