Diclofenac sodium is a potent analgesic and anti-inflammatory drug that is extensively prescribed in treatment of rheumatoid arthritis, postoperative pain, and chronic pain associated with cancer. The present study was designed to elucidate the qualitative and quantitative changes in rough endoplasmic reticulum of hepatocytes after recommended single, double and triple therapeutic dose of Diclofenac sodium in rabbits. The aim of study is to minimize the indiscriminate use of this drug in community and among physicians. Experimental study was carried at Dow University of Health Sciences (DUHS) and Sindh Institute of Urology and Transplantation (SIUT) from March 2009 to June 2010. Eighty eight healthy animals of three months age and 900~1000 gm body weight were isolated from the animal house of DUHS. These animals were divided into four groups categorized into Group A, Group B, Group C, Group D, each containing twenty two animals. Diclofenac sodium were administered intraperitoneally with the daily doses of 2, 4, and 6 mg/kg body weight for 14 consecutive days in Groups B, C and D while the control group (Group A) received normal saline. Animals were sacrificed on day fifteen and livers were removed and fixed in 4% gluterldehyde. They were processed for electron microscopy and examined under transmission electron microscope. Data was collected and subjected for statistical analysis a ‘P’ value less than 0.05 was taken as significant. It was observed that Diclofenac sodium produces significant changes in hepatocytes. There was de-granulation and swelling of the cisternae of Rough Endoplasmic Reticulum (RER) when the dose is doubled and these changes were highly significant when the dose is increased to three times the therapeutic.
Basivireddy J, Jacob M, Pulimood AB, Balasubramanian KA. Indomethacin induced renal damage: role of oxygen free radicals. Biochem Pharmacol 2004; 67(3): 587-99. http://dx.doi.org/10.1016/j.bcp.2003.09.023
Pavelka K. A comparison of the therapeutic efficacy of diclofenac in osteoarthritis: A systematic review of randomised controlled trials. Curr Med Res Opin 2012; 28(1): 163-78. http://dx.doi.org/10.1185/03007995.2011.649848
Kaur Saini M, Kaur J, Sharma P, Nath Sanyal S. Chemopreventive response of diclofenac, a non-steroidal anti-inflammatory drug in experimental carcinogenesis. Nutr Hosp 2009; 24(6): 717-23.
Taib NT, Jarrar BM, Mubarak MM. Ultrastructural alterations in renal tissues of rabbits induced by Diclofenac sodium (Voltaren). Saudi Med J 2004; 25(10): 1360-5.
Helin-Salmivaara A, Saarelainen S, Grönroos JM, Vesalainen R, Klaukka T, Huupponen R. Risk of upper gastrointestinal events with the use of various NSAIDs: a case-control study in a general population. Scand J Gastroenterol 2007; 42(8): 923-32. http://dx.doi.org/10.1080/00365520701192326
Hussain I, Khan MZ, Khan A, Javed I, Saleemi MK. Toxicological effects of diclofenac in four avian species. Avian Pathol 2008; 37(3): 315-21. http://dx.doi.org/10.1080/03079450802056439
Masubuchi Y, Nakayama S, Horie T. Role of mitochondrial permeability transition in diclofenac induced hepatocyte injury in rats. Hepatology 2002; 35(3): 544-51. http://dx.doi.org/10.1053/jhep.2002.31871
Matveev AV, Koniaeva EI. [Diclofenac sodium in osteoarthritis. Is there risk of hepatotoxicity? A systematic review
Breen EG, McNicholl J, Cosgrove E, McCabe J, Stevens FM. Fatal hepatitis associated with diclofenac. Gut 1986; 27(11): 1390-3. http://dx.doi.org/10.1136/gut.27.11.1390
O'Connor N, Dargan PI, Jones AL. Hepatocellular damage from non-steroidal anti-inflammatory drugs. QJM 2003; 96(11): 787-91. http://dx.doi.org/10.1093/qjmed/hcg138
Manov, Motanis H, Frumin I, Iancu TC. Hepatotoxicity of anti- inflammatory and analgesic drugs: Ultrastructural aspects. Acta Pharmacol Sin 2006; 27(3): 259-72. http://dx.doi.org/10.1111/j.1745-7254.2006.00278.x
Sgro C, Clinard F, Ouazir K, Chanay H, Allard C, Guilleminet C, Lenoir C, Lemoine A, Hillon P. Incidence of drug-induced hepatic injuries: French population-based study. Hepatology 2002; 36(2): 451-5. http://dx.doi.org/10.1053/jhep.2002.34857
McCaul TF, Fagan EA, Tovey G, Portmann B, Williams R, Zuckerman AJ. Fulminant hepatitis. An ultrastructural study. J Hepatol 1986; 2(2): 276-90. http://dx.doi.org/10.1016/S0168-8278(86)80087-3
Manocha S and Venkataraman S. (2000). 6th Internet World Congress for Biomedical Sciences. [online
Hayat M. Principles and Techniques of Electron Microscopy: Biological Applications. 4 ed. Cambridge: Cambridge University Press 2000.
Yasmeen T, Siddiqui IA. Amjad Z, Shoro AA, Mirza T. Alterations in mitochondria of kidney tubules by different doses of Diclofenac sodium in rabbits. Med Forum 2014; 25(1): 22-26.
Mueller D, Müller-Vieira U, Biemel KM, Tascher G, Nüssler AK, Noor F. Biotransformation of diclofenac and effects on the metabolome of primary human hepatocytes upon repeated dose exposure. Eur J Pharm Sci 2012; 45(5): 716-24. http://dx.doi.org/10.1016/j.ejps.2012.01.014
Bort R, Ponsoda X, Jover R, Gómez-Lechón MJ, Castell JV. Diclofenac toxicity to hepatocytes: a role for drug metabolism in cell toxicity. J Pharmacol Exp Ther 1999; 288(1): 65-72.
Yapar K, Attakisi O, Uzlu E, Ciliy M, Uzun M, Erdogan HM. Revue Med Vet 2008; 159(6): 363-7.
Gulsen A, Alparslan G, Meral O, Ekeram C, Nearmin K, Osman G. Histopathological Changes in Liver and Renal Tissues Induced by Different Doses of Diclofenac Sodium in Rats. Turk J Vet Anim Sci 2003; 27: 1131-1140.
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