Arch Pharm Res Vol 34, No 2, 253-259, 2011 DOI 10.1007/s12272-011-0211-3 253 Effects of Celecoxib in Young Rats: Histopathological Changes in Tissues and Alterations of Oxidative Stress/Antioxidant Defense System Sumru Sozer 1 , Gulden Diniz 2 , and Ferzan Lermioglu 1 1 Department of Toxicology, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey and 2 Behcet Uz Hospital, Pathol- ogy Laboratory, Alsancak, Izmir, Turkey (Received June 13, 2010/Revised August 3, 2010/Accepted August 8, 2010) Celecoxib is increasingly being used in children with rheumatologic complaints. Although the particular concerns about the safety of the drug, there are only a small number of published studies in children. This study was performed to investigate the effects of celecoxib on oxida- tive stress and antioxidant enzyme activities as well as celecoxib-induced changes in liver, kidneys and stomach of young rats. Four weeks-old Wistar albino, female rats were used. Celecoxib was given by gavage for 14 days. Control rats received only vehicle. Blood and organs were taken under pentobarbital anesthesia. Plasma malondialdehyde levels were increased by treatment. Catalase activity was increased, while glutathione peroxidase activity was decreased. Superoxide dismutase and glucose-6-phosphate dehydrogenase activities was not changed by treatment. The reduced glutathione content of kidneys were higher, while there was no significant difference in liver content, as compared with controls. Significant changes were observed in serum parameters of rats treated with celecoxib. Histopathological evaluation of organs was done by an experienced pathologist unaware of the treatment. Results of the present study indicated the alterations of oxidant/antioxidant status and histo- pathological changes in tissues of young rats treated with celecoxib. Key words: Celecoxib, Antioxidant defense system, Young rats INTRODUCTION Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs for the treat- ment of rheumatic diseases and other musculoskeletal disorders. They reduce pain and inflammation by in- hibiting cyclooxygenase enzymes (COX), which are needed for the synthesis of prostaglandins (PGs) from arachidonic acid (Vane, 1971). The COX enzymes com- prise two structurally related isoforms, COX-1 and COX-2. COX-1 is the major COX isoform and is nor- mally expressed in the stomach, whereas COX-2 is ex- pressed at very low levels in most tissues but is rapidly induced at sites of inflammation (Vane et al., 1994; Crofford, 1997; Ferraz et al., 1997). It has been postul- ated that NSAIDs act as anti-inflammatory agents by inhibiting COX-2 and that their side effects on gastr- ointestinal tract and kidneys are due to inhibition of COX-1. Therefore, selective COX-2 inhibitors were developed to reduce the adverse effects on gastrointest- inal tract and kidneys (Arai et al., 1993; Kargman et al., 1996). Celecoxib, a NSAID, is the first FDA approved medi- cation in a new class of arthritis drugs known as COX- 2 selective inhibitors. Celecoxib is a low-solubility and highly permeable drug with good oral bioavailability and low first-pass metabolism in either the gut or liver. The apparent volume of distribution at steady state is approximately 400 L, suggesting extensive distribution into the tissues (Stempak et al., 2002). In experimental studies, the drug was distributed pri- marily to the gastrointestinal tract, but high concen- trations were also observed in other tissues including the liver. No accumulation phenomenon was observed with celecoxib (Paulson et al., 2000). Celecoxib appears to exert reduced adverse effects compared with tradi- Correspondence to: Ferzan Lermioglu, Department of Toxicol- ogy, Faculty of Pharmacy, Ege University, Bornova, Izmir, Tur- key Tel: 90 232 3739173, Fax: 90 232 3885258 E-mail: ferzan.lermioglu@ege.edu.tr or ferzush@yahoo.com