Back
 JBM  Vol.7 No.12 , December 2019
Diclofenac-Induced Kidney Damage in Wistar Rats: Involvement of Antioxidant Mechanism
Abstract: Kidney damage has been associated with administration diclofenac, a phenylacetic acid derivative belonging to the nonsteroidal anti-inflammatory drugs (NSAIDs), which is commonly used for the treatment of various diseases such as rheumatoid arthritis, ankylosing spondylitis, acute muscle pain conditions and osteoarthritis. This study investigated the exact mechanism of diclofenac in renal toxicity by determining the involvement of oxidative stress in rats. Adult male Wistar rats were divided into two groups of eight rats in each group and orogastrically treated for three days. Group 1 served as the normal control and received normal saline (0.9% w/v) and group 2 received 40 mg/kg body weight of diclofenac for three days. Administration of diclofenac caused degeneration of the kidney of rats as evidenced by significant elevation in the serum levels of creatinine, urea, albumin, uric acid, protein and electrolytes and the activities of renal-5’-nucleotidase and glucose-6-phosphate-dehydrogenase (G6PDH) compared with control. Furthermore, administration of diclofenac decreased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) and the level of glutathione with concomitant increase in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in the kidney of the diclofenac treated groups compared with control. These findings reveal that administration of diclofenac may impair kidney functions through induction of oxidative stress.
Cite this paper: Abiola, T. , Adebayo, O. and Babalola, O. (2019) Diclofenac-Induced Kidney Damage in Wistar Rats: Involvement of Antioxidant Mechanism. Journal of Biosciences and Medicines, 7, 44-57. doi: 10.4236/jbm.2019.712005.
References

[1]   Sembuling, K. and Sembuling, P. (2012) Essential of Medical Physiology. 6th Edition, New Jaypee Brothers Medical Publishers, Delhi, India.

[2]   Ungprasert, P., Cheungpasitporn, W., Crowson, C.S. and Matteson, E.L. (2015) Individual Non-Steroidal Anti-Inflammatory Drugs and Risk of Acute Kidney Injury: A Systematic Review and Meta-Analysis of Observational Studies. European Journal International Medicine, 26, 285-291.
https://doi.org/10.1016/j.ejim.2015.03.008

[3]   Zhang, X., Donnan, P.T., Bell, S., et al. (2017) Non-Steroidal Anti-Inflammatory Drug Induced Acute Kidney Injury in the Community Dwelling General Population and People with Chronic Kidney Disease: Systematic Review and Meta-Analysis. BMC Nephrology, 18, 256.
https://doi.org/10.1186/s12882-017-0673-8

[4]   Walter Horl, H. (2010) Nonsteroidal Anti-Inflammatory Drugs and the Kidney. Pharmaceuticals, 3, 2291-2321.
https://doi.org/10.3390/ph3072291

[5]   Dhanvijay, P., Arup Misra, K. and Sushil Varma, K. (2013) Diclofenac Induced Acute Renal Failure in Adecompensated Elderly Patient. Journal of Pharmacology and Pharmacothereutics, 4, 155-157.
https://doi.org/10.4103/0976-500X.110916

[6]   Bosch-Marcé, M., Clària, J., Titos, E., Masferrer, J.L., Altuna, R., Poo, J.L., et al. (1999) Selective Inhibition of Cyclooxygenase 2 Spares Renal Function and Prostaglandin Synthesis in Cirrhotic Rats with Ascites. Gastroenterology, 116, 1167-1175.
https://doi.org/10.1016/S0016-5085(99)70020-X

[7]   Blair, H.A. and Plosker, G.L. (2015) Diclofenac Sodium Injection (Akis, Dicloin): A Review of Its Use in the Management of Pain. Clinical and Drug Investigation, 35, 397-404.
https://doi.org/10.1007/s40261-015-0294-6

[8]   Hoy, S.M. (2016) Diclofenac Sodium Bolus Injection (DylojectTM): A Review in Acute Pain Management. Drugs, 76, 1213-1220.
https://doi.org/10.1007/s40265-016-0619-7

[9]   Hossain, M.K., Khatun, A., Rahman, M., Akter, M.N., Chowdhury, S.A. and Alam, S.M. (2016) Characterization of the Effect of Drug-Drug Interaction on Protein Binding in Concurrent Administration of Sulfamethoxazol and Diclofenac Sodium Using Bovine Serum Albumin. Advanced Pharmacology Bulletin, 6, 589.

[10]   Lonappan, L., Brar, S.K., Das, R.K., Verma, M. and Surampalli, R.Y. (2016) Diclofenac and Its Transformation Products: Environmental Occurrence and Toxicity—A Review. Environmental International, 96, 127-138.
https://doi.org/10.1016/j.envint.2016.09.014

[11]   Ahmed, A.Y., Gad, A.M. and El-Raouf, M.A.O. (2017) Curcumin Ameliorates Diclofenac Sodium-Induced Nephrotoxicity in Male Albino Rats. Journal of Biochemistry and Molecular Toxicology, 31, e21951.
https://doi.org/10.1002/jbt.21951

[12]   Nouri, A. and Heidarian, E. (2019) Nephroprotective Effect of Silymarin against Diclofenac-Induced Renal Damage and Oxidative Stress in Male Rats. Journal of Herbmed Pharmacology, 8, 146-152.
https://doi.org/10.15171/jhp.2019.23

[13]   Public Health Service (1996) Policy on Humane Care and Use of Laboratory Animals. US Department of Health and Human Services, Washington DC.

[14]   Fawcett, J.K. and Scott, J.E. (1960) A Rapid and Precise Method for the Determination of Urea. Journal of Clinical Pathology, 13, 156-159.
https://doi.org/10.1136/jcp.13.2.156

[15]   Henry, R.J. (1974) Clinical Chemistry, Principles and Techniques. 2nd Edition, Harper and Row, Hagerstown, MD.

[16]   Tietz., N. (1995) Clincal Guide to Laboratory Tests. 3rd Edition, WB. Saunders, Philadelphia, PA, 268-273.

[17]   Fossati, P., Prencipe, L. and Berti, G. (1980) Use of 3,5-Dichloro-2-Hydroxybenze-nesulfonic Acid/4-Aminophenazone Chromogenic System in Direct Enzymic Assay of Uric Acid in Serum and Urine. Clinical Chemistry, 26, 227-231.
https://doi.org/10.1287/mnsc.26.2.227

[18]   Webster, D. (1997) Biochemical Parameters and Its Assay. Clinical Chemistry, 23, 663-665.

[19]   George Goodland, A.J. and Catherine Clark, M. (1982) Alteration in Hepatic 5’-Nucleotidase in Tumor Bearing Rat. Enzyme, 27, 119-123.
https://doi.org/10.1159/000459035

[20]   Misra, H.P. and Fridovich, I. (1972) The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase. The Journal of Biological Chemistry, 247, 3170-3175

[21]   Aebi, H. (1984) Catalase in Vitro. Methods Enzymology, 105, 121-126.
https://doi.org/10.1016/S0076-6879(84)05016-3

[22]   Rotruck, J.T., Pope, A.L., Ganther, H.E., Swanson, A.B. and Hoekstra, W.G. (1973) Selenium: Biochemical Role as a Component of Glutathione Peroxidase. Science, 179, 588-590.
https://doi.org/10.1126/science.179.4073.588

[23]   Habig, W.H., Pabst, M.J. and Jakoby, W.B. (1974) Glutathione S-Transferase; The First Enzymatic Step Inmercapturic Acid Formation. Journal Biological Chemistry, 249, 7130-7139.

[24]   Jollow, D.J., Mitchell, J.R., Zampaglione, N. and Gillette, J.R. (1974) Bromobenzene Induced Liver Necrosis: Protective Role of Glutathione and Evidence for 3,4-Bromobenzene Oxide as the Hepatotoxic Metabolite. Pharmacology, 11, 151-169.
https://doi.org/10.1159/000136485

[25]   Buege, J.A. and Aust, S.D. (1978) Microsomal Lipid Peroxidation. Method Enzymology, 30 302-310.
https://doi.org/10.1016/S0076-6879(78)52032-6

[26]   Wolff, S.P. (1994) Ferrous Ion Oxidation in Presence of Ferric Ion Indicator Xylenol Orange for Measurement of Hydroperoxides. Methods Enzymology, 233, 182-189.
https://doi.org/10.1016/S0076-6879(94)33021-2

[27]   Gornall, A.G., Bardawill, C.J. and David, M.M. (1949) Determination of Serum Proteins by Means of the Biuret Reaction. Journal of Biological Chemistry, 177, 751-766.

[28]   Bancroft, J.D. and Gamble, M. (2008) Theory and Practice of Histology Techniques. 6th Edition, Churchill Livingstone Elsevier, London, 83-134.

[29]   Naidoo, S. (2015) Drug and Kidney. South African Medical Journal, 105, 322.
https://doi.org/10.7196/SAMJ.9537

[30]   Adedara, I.A., Teberen, R., Ebokaiwe, A.P., Ehwerhemuepha, T. and Farombi, E.O. (2012) Induction of Oxidative Stress in Liver and Kidney of Rats Exposed to Nigerian Bonny Light Crude Oil. Environmental Toxicology, 27, 372-379.
https://doi.org/10.1002/tox.20660

[31]   Komhoff, M.A., Grone, H.J., Klein, T.H., Seyberth, H.W. and Nusing, R.M. (1997) Localization of Cyclooxygenase-1 and-2 in Adult and Fetal Human Kidney: Implication for Renal Function. American Journal of Physiology-Renal Physiology, 272, F460-F468.
https://doi.org/10.1152/ajprenal.1997.272.4.F460

[32]   Fattori, V., Sergio Borghi, M., Carla Guazelli, F.S., Andressa Giroldo, C., Crespigio, J., Allan Bussmann, J.C., Coelho-Silva, L., Natasha Ludwig, G., Tania Mazzuco, G., Casagrande, R. and Waldiceu Verri Jr., A. (2017) Vinpocetine Reduces Diclofenac-Induced Acute Kidney Injury through Inhibition of Oxidative Stress, Apoptosis, Cytokine Production, and NF-κB Activation in Mice. Pharmacological Research, 120, 10-22.
https://doi.org/10.1016/j.phrs.2016.12.039

[33]   Borghi, S.M., Fattori, V., Ruiz-Miyazawa, K.W., Bertozzi, M.M., Louren-co-Gonzalez, Y., Tatakihara, R.I., et al. (2018) Pyrrolidine Dithiocarbamate Inhibits Mouse Acute Kidney Injury Induced by Diclofenac by Targeting Oxidative Damage, Cytokines and NF-κB Activity. Life Science, 208, 221-231.
https://doi.org/10.1016/j.lfs.2018.07.038

[34]   Ali Nouri, E.H. (2019) Nephroprotective Effect of Silymarin against Diclofenac-Induced Renal Damage and Oxidative Stress in Male Rats. Journal of Herbmed Pharmacology, 8, 146-152.
https://doi.org/10.15171/jhp.2019.23

[35]   Finn, W. and Porter, G. (2003) Urinary Biomarkers and Nephrotoxicity. Clinical Nephrotoxins, 2nd Edition, Kluwer Academic Publishers, Philip Drive Norwell, MA, 621-655.
https://doi.org/10.1007/1-4020-2586-6_33

[36]   Tojo, A. and Kinugasa, S. (2012) Mechanisms of Glomerular Albumin Filtration and Tubular Reabsorption. International Journal of Nephrology, 2012, Article ID: 481520.
https://doi.org/10.1155/2012/481520

[37]   Al-Snafi, A.E. (2015) Therapeutic Properties of Medicinal Plants: A Review of Their Detoxification Capacity and Protective Effects (Part 1). Asian Journal of Pharmaceutical Science and Technology, 5, 257-270.

[38]   Tremellen, K. (2008) Oxidative Stress and Male Infertility—A Clinical Perspective. Human Reproductive Update, 14, 243-258.
https://doi.org/10.1093/humupd/dmn004

[39]   Nouri, A., Heidarian, E. and Nikoukar, M. (2017) Effects of N-Acetyl Cysteine on Oxidative Stress and TNF-α Gene Expression in Diclofenac-Induced Hepatotoxicity in Rats. Toxicological Mechanism Methods, 27, 561-567.
https://doi.org/10.1080/15376516.2017.1334732

[40]   El-Maddawy, Z.K. and El-Ashmawy, I.M. (2013) Hepato-Renal and Hematological Effects of Diclofenac Sodium in Rats. Global Journal of Pharmacology, 7, 123-132.

[41]   Calabrese, E.J. and Iavicoli, I.V. (2013) Calabrese, Hormesis: Its Impact on Medicine and Health. Human Experimental Toxicology, 32, 120-152.
https://doi.org/10.1177/0960327112455069

[42]   Masella, R., Di Benedetto, R., Vari, R., Filesi, C. and Giovannini, C. (2005) Novel Mechanisms of Natural Antioxidant Compounds in Biological Systems: Involvement of Glutathione and Glutathione Related Enzymes. Journal of Nutritional Biochemistry, 16, 577-586.
https://doi.org/10.1016/j.jnutbio.2005.05.013

[43]   Bauche, F., Fouchard, M.H. and Jegou, B. (1994) Antioxidant System in Rat Testicular Cells. FEBS Letter, 349, 392-396.
https://doi.org/10.1016/0014-5793(94)00709-8

[44]   Doreswamy Muralidhara, K. (2005) Genotoxic Consequences Associated with Oxidative Damage in Testis of Mice Subjected to Iron Intoxication. Toxicology, 206, 169-178.
https://doi.org/10.1016/j.tox.2004.07.010

[45]   Klaunig, J.E., Kamendulis, L.M. and. Hocevar, B.A. (2010) Oxidative Stress and Oxidative Damage in Carcinogenesis. Toxicological Pathology, 38, 96-109.
https://doi.org/10.1177/0192623309356453

 
 
Top