Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 32722
Histopathological Alterations in Liver of Mice Exposed to Different Doses of Diclofenac Sodium

Authors: Deepak Mohan, Sushma Sharma


Diclofenac sodium, a member of the acetic acid family of non-steroidal anti-inflammatory drugs, is used to retard inflammation, arthritis pain and ankylosing spondylitis. The drug is known to cause severe injury in different tissues due to formation of reactive oxygen species. The present study is focused on the effect of different doses of diclofenac (4 mg/kg/body weight and 14 mg/kg/body weight on histoarchitecture of the liver from 7-28 days of the investigation. Diclofenac administration resulted in distorted hepatic degeneration and formation of wide areas in the form of sinusoidal gaps. Hepatic fibrosis noticed in different stages of investigation could be attributed to chronic inflammation and reactive oxygen species which results in deposition of extracellular matrix proteins. The abrupt degenerative changes observed during later stages of the experiment showed maximum damage to the liver, and there was enlargement of sinusoidal gaps accompanied by maximum necrosis in the tissues.

Keywords: Arthritis, diclofenac, histoarchitecture, sinusoidal.

Digital Object Identifier (DOI):

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 1090


[1] J. L. Oaks, M. Gilbert, M. Z. Virani, R. T. Watson, C. U. Meteyer, B. A. Rideout, H. L. Shivaprasad, S. Ahmad, M. J. Chaudhary, M. Arshad, S. Mahmood, A. Ali and A. A. Khan, “Diclofenac residues as the cause of vulture population decline in Pakistan” Nature. 427(6975): 2004 pp 596-598.
[2] D. Mohan and S. Sharma, “Biochemical changes in liver of mice after exposure to different doses of diclofenac sodium” International Journal of Biological, Biomolecular, Agricultural, Food and Biotechnological Engineering” 2(5): 2017.
[3] R. Bort, X. Pondosa, R. Jover, M. J. Gomez-Lechon and J. V. Castell “Diclofenac toxicity to hepatocytes: A role for drug metabolism in cell toxicity” J. Pharmacol. Exp. Ther. 288: 1999 pp 65-72.
[4] G. Aydin, A. Gokcimen, M. Oncu, E. Cicek, N. Karahan and O. Gokalp. “Histopathologic changes in liver and renal tissues induced by different doses of Diclofenac sodium in rats.” Turk. J. Vet. Anim. Sci. 27:2003 pp 1131-1140.
[5] G. S. Ouellette, B. E. Slitzky J. A Gates, S. Lagarde, S and A.B. West, “Reversible hepatitis associated with diclofenac.” J. Clin. Gastroenterol. 13(2): 1991 pp. 205-210.
[6] W. Tang, R. A. Stearns, S. M. Bandiera, Y. Zhang, C. Rabb, M. P. Braun, D. C. Dean, J. Rang, K. H. Leung, G. A. Doss, J. Strauss, G. Kwei, T. Rushmore, S. Chiu, and T. Baillic, “Studies on cytochrome P-450 mediated bio-activation of Diclofenac in rats and in human hepatocytes: identification of glutathione conjugated metabolites”. Drug Metab. Dispos. 27(3):1999 pp. 365-372.
[7] Z. Tomic, B. Milijasevic, A. Sabo, L. Dusan, V. Jakovljevic, M. Mikov, S. Majda, and V. Vasovic. “Diclofenac and ketoprofen liver toxicity in rat.” Eur. J. drug Metab. Pharmacokinet. 33(4): 2008 pp. 253-260.
[8] M. Moorthy, S. Fakura and H. Ithnin, “The histomorphological analysis of liver following administration of low doses of diclofenac and ibuprofen” J. Biol. Sci. 9(7): 2009 pp. 676-681.
[9] A. H. Alaaeldin, “Ameliorative effects of Moringa oleifera Lam seed extract on liver fibrosis in rats”. Food Chem. Toxicol. 48(1): 2010 pp. 345-355.
[10] F. Sigala, G. Kostopanagiotou, I. Andreadou, N. Kavatzas, E. Felekouras, P. Sigalas, E. Bastounis, and E. Papalambros, “Histological and lipid peroxidation changes after administration of 2- acetylaminofluorene in a rat liver injury model following selective periportal and pericentral damage.” Toxicol. 1196(1-2):2004 pp. 155-163
[11] Z. K. El-Maddawy, and M. I. El- Ashmawy, “Hepato-renal and haematological effects of diclofenac sodium to rats” Global J. Pharmacol. 7(2): 2013 pp. 123-132.
[12] D. A. Kertz-Romell, and U. A. Boelsterli, “Diclofenac covalent protein binding is dependent on acyl glucuronide formation and is inversely related to P 450 mediated acute cell injury in cultured rat hepatocytes”. Toxicol. Appl. Pharmacol. 120: 1993 pp. 155-161.
[13] K. P. Rao, “Recent developments of collagen based materials for medical applications and drug delivery systems”. J.Biomater. Sci. Polym.. 7(7): 1995 pp. 623-645.
[14] K. Ramalingam, and S. Subramanian, “Sex differences in delayed hypersensitivity response in Wistar rats Rattus norvegicus to CFA” Utter Pradesh J. Zool. 22(1): 2002 pp. 85-88.
[15] N. T. Taib, and B. M. Jarrar “Histochemical alterations in the spleen of rabbits induced by diclofenac sodium (Voltaren)” J. King Saud. Univ. Sci. 19(1): 2006 pp. 21-29.
[16] N. Somchit, F. Sanat, E. H. Gan, I. A. W. Saharin, and A. Zuraini. “Liver injury induced by the non-steroidal anti-inflammatory drug mefenamic acid” Singapore Med. J. 45(11):2004 pp. 530-532.