2 Current Drug Therapy, 2009, 4, 2-6 1574-8855/09 $55.00+.00 ©2009 Bentham Science Publishers Ltd. Anti Oxidant Property of New Cephalosporin-Aminoglycoside Fixed Dose Combination Manu Chaudhary, Arvind Soni, Vivek Kumar Dwivedi * and Rajesh Sehgal Intellectual Scientific Division, Venus Medicine Research Centre, Hill Top Industrial Estate, Bhatoli Kalan, Baddi, H.P.- 173205, India Abstract: Aminoglycosides are known to cause oxidative stress related toxicities and tissue injuries. Present study was planned to evaluate the effect of aminoglycosides on blood oxidative stress parameters in mice and free radical scaveng- ing potential of cephalosporins, when combined as a single injection with aminoglycosides using chemical vector medi- ated technology. Mus musculus mice were divided into five groups: Control group animals (treated with normal saline), amikacin treated group, tobramycin treated group, cefepime + amikacin treated group and ceftazidime + tobramycin treated group. A significant improvement in superoxide dismutase (SOD), catalase activities, along with malonaldialde- hyde (MDA) levels and creatinine levels were observed in fixed dose combination of cephalosporins and aminoglycosides treated groups as compared to aminoglycosides alone (amikacin and tobramycin) treated groups. These findings indicate that on combining cephalosporins with aminoglycosides using chemical vector mediated technology prevents oxidative stress related tissues injury induced by aminoglycosides. Key Words: Cephalosporin, aminoglycoside, free radicals, catalase, superoxide dismutase, malonaldialdehyde. INTRODUCTION Aminoglycosides are important drugs in clinical use, but these antibiotics are potentially ototoxic and nephrotoxic at levels only slightly above therapeutic range [1,2]. Approxi- mately 5-10% of the people, who are treated with aminogly- cosides experience such toxic effects. The toxicity of amino- glycosides has been widely studied [3]. These aminoglyco- sides are polycationic in nature that cause oxidative stress in living cells [4]. Free radicals play an important role in drug- induced damage to the liver, kidneys and other organs [5]. There are various reports suggesting that aminoglycosides causes ototoxicity [6] and nephrotoxicity [7] due to oxidative stress. The binding of aminoglycosides in vivo as well as in vitro with negatively charged membranes is associated with impairment of phospholipid catabolism, change in membrane permeability, membrane aggregation [8] and reduces the activities of phospholipases [9,10]. The adverse effect of aminoglycosides has been attributed to the development of an array of alterations in proximal tubule epithelium fol- lowed by its destruction, thereby causing kidney dysfunction [11]. Aminoglycosides in combination with cephalosporins synergistically kill various pathogens and broaden the bacte- ricidal spectrum against Gram positive and gram negative bacteria. Cefepime and ceftazidime are cephalosporin class of antibiotics and having free radical scavenging potential [12]. Chemical vector mediated technology is used to pro- vide compatibility of cephalosporins and aminoglycosides without interfering in the pharmacokinetic property of drug component and prevents the oxidation of methionine group and thiazolidine and dihyrothiazine present in antibiotics [13]. The component(s) of chemical vector possess free radi- *Address correspondence to this author at the Venus Medicine Research Centre, Hill Top Industrial Estate, Bhatoli Kalan, Baddi, H.P. - 173205 India; Tel: 91-1795-302127; Fax: 91-1795 302133; E-mail: vivekdwivedi@venusremedies.com cal scavenging potential that leads to reduction in oxidative stress. The objective of the present study was to evaluate the effect of aminoglycosides on blood oxidative stress parame- ters in mice and free radical scavenging potential of cepha- losporins, when combined as a single injection with amino- glycosides using chemical vector mediated technology. MATERIALS AND METHODS Chemicals All the biochemicals used in the present study were pro- cured from Sigma, St. Louis, MO, USA. Other chemicals purchased locally were of analytical grade. All the antibiotics such as amikacin, tobramycin, cefepime plus amikacin (Po- tentox) and ceftazidime plus tobramycin (Tobracef) were obtained from Venus Remedies Ltd. India. The ratio of fixed dose combination of cefepime + amikacin and cefetazidime + tobramycin were 4:1 and 11:1 respectively. Animals and Treatments Twenty Mus musculus mice (age 3.5 to 4.0 months; weighing 30 ± 5 g) were used in the experiment. The mice were fed standard pelleted diet and sterile water ad libitum. The mice were divided into five groups of four mice each as given below. Control group (isotonic saline treated group) Amikacin sulphate treated group (28.5 mg/Kg body weight/ day) Tobramycinsulphate treated group (4.0 mg//Kg body weight/ day) Ceftazidime plus Tobramycin treated group (34.1mg/Kg body weight/day) Cefepime plus Amikacin fixed dose combination treated group (35.7mg/Kg body weight/day)