Environmental Toxicology and Pharmacology 22 (2006) 85–89 Subacute toxicity of celecoxib on thyroid and testis of rats: Hormonal and histopathological changes G¨ uldeniz Selmano˘ glu a,∗ , E. Arzu Koc ¸kaya b , M. Turan Akay a , Kemal Kismet c a Hacettepe University, Faculty of Science, Department of Biology, 06800 Beytepe Campus, Ankara, Turkey b Gazi University, The Higher Vocational School of Health Services, G¨ olba¸ sı Campus, 06830 G ¨ olba¸ sı, Ankara, Turkey c Ankara Training and Research Hospital, 4th General Surgery Clinic, Ulucanlar, Ankara, Turkey Received 17 July 2005; accepted 13 December 2005 Available online 20 January 2006 Abstract Celecoxib is an effective agent in the treatment of signs and symptoms of inflammation, rheumatoid arthritis and osteoarthritis. The purpose of this study is to assess the effects of two different doses of celecoxib on some hormones and endocrine glands of male rats. In this study, the doses of 10 and 50mg/kg/day of celecoxib were given to male rats orally for 28 days. At the end of the study, serum total triiodothyronine (T 3 ), total thyroxine (T 4 ), thyroid stimulating hormone (TSH), testosterone and luteinizing hormone (LH) levels of rats were analyzed by radioimmunoassay technique using RIA kits. Thyroid and testis tissues of male rats were examined histopathologically. While there was no a change in serum T 3 ,T 4 and LH levels of celecoxib-treated rats, there were differences in serum TSH and testosterone levels of rats treated with 50mg/kg/day celecoxib for 28 days compared with those of control rats. In histopathological examinations, celecoxib-related changes were found in thyroid glands of the rats. © 2006 Elsevier B.V. All rights reserved. Keywords: Celecoxib; Histopathology; Hormone levels; Rat; Testis; Thyroid 1. Introduction Beginning with the discovery of aspirin just over 100 years ago, nonsteroidal antiinflammatory drugs (NSAIDs) have evolved as effective analgesics, antiinflammatories and antipyretics (Lipsky, 1999). NSAIDs are prescribed for a wide variety of indications (Garnett, 2001). Commonly prescribed drugs including anticonvulsants, beta-adrenergic receptor antag- onists, steroid hormones and heparin may result in abnormal thyroid function tests without clinical features of thyroid dys- function. Many drugs have marked effects on the synthesis, transport and metabolism of thyroid hormones (Davies and Franklyn, 1991; Quin and Thomson, 1994). NSAIDs can affect thyroid function tests but rarely cause overt thyroid disease. They are known to interfere with plasma protein binding of thyroid hormones (Quin and Thomson, 1994). Testing of thyroid func- ∗ Corresponding author. Tel.: +90 312 297 64 33; fax: +90 312 299 20 28. E-mail address: guldeniz@hacettepe.edu.tr (G. Selmano ˘ glu). tion is common in clinical practice. The pathways of thyroid hormone synthesis, secretion, transport in the circulation, and metabolism offer numerous targets for drug interaction (Surks and Sievert, 1995). Measurement of serum thyroid stimulat- ing hormone (TSH) is the single best test of thyroid function, because of the sensitivity of TSH secretion to very small changes in serum total triiodothyronine (T 3 ) and total thyroxine (T 4 ) con- centrations. In addition, some drugs have direct effects on the secretion of TSH by the anterior pituitary (Davies and Franklyn, 1991). Several studies indicated that drugs interfering with prostaglandin (PG) metabolism, such as NSAIDs, might affect male reproductive functions (Barkay et al., 1984; Knuth et al., 1989; Kwan et al., 1992; Stutz et al., 2000; Tilakaratne and Soory, 2002). Barkay et al. (1984) found that the treat- ment with indomethacin and ketoprofen in oligospermic patients increased sperm count, sperm motility and fertilizing capac- ity. The radioimmunoassay examination showed an increase in plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) but a decrease in testosterone of these patients. However, in another study, Knuth et al. (1989) did not found 1382-6689/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.etap.2005.12.004