EVALUATION OF HEPATOTOXIC AND NEPHROTOXIC EFFECTS OF PIROXICAM SULFONATED DERIVATIVES

Authors

  • Asif Ali , Assistant Professor of Pathology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan
  • Ghazala Shaheen Institute of Basic Medical Sciences, Khyber Medical University
  • Shafiq Ahmad Tariq Institute of Basic Medical Sciences, Khyber Medical University
  • Safi Ullah Department of Pharmacy, University of Peshawar
  • Nuzhat Sultana Khyber Medical College, Peshawar, Pakistan
  • Naeem Khan Institute of Basic Medical Sciences, Khyber Medical University
  • Inayat Shah Institute of Basic Medical Sciences, Khyber Medical University
  • Syed Muhammad Ashad Halimi Department of Pharmacy, University of Peshawar
  • Muhammad Saeed Department of Pharmacy, University of Peshawar
  • Syed Hamid Habib Institute of Basic Medical Sciences, Khyber Medical University

DOI:

https://doi.org/10.69656/pjp.v13i4.282

Keywords:

Nephrotoxicity, Piroxicam, Hepatotoxicity

Abstract

Background: Pain management requires new pharmacotherapy with good efficacy and less side effects. Piroxicam is used routinely in clinical practice but it is associated with side effects. To minimize the chances of adverse effects, sulfonated piroxicam derivatives (SPD) have been introduced. We sought to find hepatotoxic and nephrotoxic effects of SPD in Albino rats. Methods: An experimental study on SPD was carried out at the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar. Healthy 24 albino rats were divided into 5 groups. One control group and four experimental groups (compound I and II, each with a dose of 10mg/kg and 20mg/kg) received treatment for 7 days. Liver function tests (LFTs), renal function tests (RFTs) and histology of liver and kidney specimens was performed after culling rats. The difference between median values of samples was assessed using Kruskal-Wallis test with post-hoc (for LFTs and RFTs). SPSS-21 was used for all statistical analysis and p≤0.05 was considered statistically significant. Results: The alanine aminotransferase (ALT) values were significantly high in the 20 mg/Kg group than control for both compounds (p=0.03, p=0.001 respectively). The aspartate aminotransferase (AST) values were significantly high in the 10 mg/Kg and 20 mg/Kg group than control for compounds II (p=0.01, p=0.0001 respectively). The alkaline phosphatase (ALP) values were significantly high in the 20 mg/Kg group than control for compounds II (p=0.002). The blood urea values were significantly high in the 20 mg/Kg group than control for compounds II (p=0.008). The mean final score of liver injury in all experimental groups (mean range 5–7) was less suggesting that the damage in liver was less pronounced. Renal injury was more pronounced in the 20 mg/Kg dose for both compound I and compound II (mean score 7) compared to 10 mg/Kg dose (mean score 4). Conclusion: Piroxicam sulfonated derivatives can cause focal changes in liver and kidney which might be reversible. The changes are less pronounced for compound I with a low dose.

Pak J Physiol 2017;13(4):18–22

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References

1. Lumley MA, Cohen JL, Borszcz GS, Cano A, Radcliffe AM, Porter LS, et al. Pain and emotion: a biopsychosocial review of recent research. J Clin Psychol 2011;67(9):942–68.
2. Veehof MM, Oskam M-J, Schreurs KM, Bohlmeijer ET. Acceptance-based interventions for the treatment of chronic pain: a systematic review and meta-analysis. Pain 2011;152(3):533–42.
3. Borsook D, Hargreaves R, Bountra C, Porreca F. Lost but making progress—Where will new analgesic drugs come from? Sci Transl Med 2014;6(249):249sr3–sr3.
4. Moore A, Derry S, Eccleston C, Kalso E. Expect analgesic failure; pursue analgesic success. BMJ 2013;346.
5. Brune K, Patrignani P. New insights into the use of currently available non-steroidal anti-inflammatory drugs. J Pain Res 2015;8:105.
6. Trivedi M. Spectroscopic characterization of disulfiram and nicotinic acid after biofield treatment. J Anal Bioanal Tech 2015;6:265.
7. Laine L. NSAID-associated gastrointestinal bleeding: assessing the role of concomitant medications. Gastroenterology 2014;147(4):730–3.
8. Roubille C, Martel-Pelletier J, Davy J-M, Haraoui B, Pelletier J-P. Cardiovascular adverse effects of anti-inflammatory drugs. Antiinflamm Antiallergy Agents Med Chem 2013;12(1):55–67.
9. Kowalski ML, Makowska J, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti‐inflammatory drugs (NSAIDs)―classification, diagnosis and management: review of the EAACI/ENDA and GA2LEN/HANNA. Allergy 2011;66(7):818–29.
10. Buer JK. Origins and impact of the term ‘NSAID’. Inflammopharmacology 2014;22(5):263–7.
11. van Esch RW, Kool MM, van As S. NSAIDs can have adverse effects on bone healing. Med Hypotheses 2013;81(2):343–6.
12. Ilic S, Drmic D, Franjic S, Kolenc D, Coric M, Brcic L, et al. Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions. Life Sci 2011;88(11):535–42.
13. Möller B, Pruijm M, Adler S, Scherer A, Villiger PM, Finckh A. Chronic NSAID use and long-term decline of renal function in a prospective rheumatoid arthritis cohort study. Ann Rheum Dis 2015;74(4):718–23.
14. Jiang Y, Gu L, Zhang R, Zhang Y, Zhang L, Ju P, et al. Evaluation of the indicative roles of seven potential biomarkers on hepato-nephrotoxicity induced by Genkwa Flos. J Ethnopharmacol 2014;158:317–24.
15. Ullah S, Saeed M, Halimi SMA, Fakhri MI, Khan KM, Khan I, et al. Piroxicam sulfonates biology-oriented drug synthesis (BIODS), characterization and anti-nociceptive screening. Med Chem Res 2016;25(7):1468–75.
16. Mehren KG. Exotic Companion Medicine Handbook for Veterinarians. Can Vet J 1999;40(4):275–6.
17. Gökakın AK, Atabey M, Deveci K, Sancakdar E, Tuzcu M, Duger C, et al. The effects of sildenafil in liver and kidney injury in a rat model of severe scald burn: a biochemical and histopathological study. Ulus Travma Acil Cerrahi Derg 2014;20(5):319–27.
18. Wilk W, Zimmermann TJ, Kaiser M, Waldmann H. Principles, implementation, and application of biology-oriented synthesis (BIOS). Biol Chem 2010;391(5):491–7.
19. Manohara C, Sanganal S, Prem K, Swamy K, Phani A. Improved dissolution rate of Piroxicam by fusion solid dispersion technique. Sci Tech Arts Res J 2014;3(1):44–7.
20. Yadav N, Dixit V. Hepatoprotective activity of leaves of Kalanchoe pinnata Pers. J Ethnopharmacol 2003;86(2):197–202.
21. Sureshkumar S, Mishra S. PHCOG MAG. Research Article Hepatoprotective activity of extracts from Pergularia daemia Forsk against carbon tetrachloride-induced toxicity in rats. Phcog Mag 2007;3(11):187.
22. Eidi A, Mortazavi P, Bazargan M, Zaringhalam J. Hepatoprotective activity of cinnamon ethanolic extract against CCI4-induced liver injury in rats. Excli J 2012;11:495.
23. Farooq Y, Khan MA, Farooq MA. Liver function tests, red cell indices and oxidative stress in healthy male Sprague Dawley rats. Pak J Physiol 2015;11(3):10–3.
24. Mossalam HH, yhtaF Yousuf A. Hepatotoxic potential of leflunomide drug in adult male albino rats. AAMJ 2013;11:284–309.
25. Mershiba SD, Dassprakash MV, Saraswathy SD. Protective effect of naringenin on hepatic and renal dysfunction and oxidative stress in arsenic intoxicated rats. Mol Biol Rep 2013;40(5):3681–91.
26. Berger K, Moeller MJ, editors. Mechanisms of epithelial repair and regeneration after acute kidney injury. Semin Nephrol 2014;34(4):394–403.

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Published

31-12-2017

How to Cite

1.
Ali A, Shaheen G, Tariq SA, Ullah S, Sultana N, Khan N, et al. EVALUATION OF HEPATOTOXIC AND NEPHROTOXIC EFFECTS OF PIROXICAM SULFONATED DERIVATIVES. Pak J Phsyiol [Internet]. 2017 Dec. 31 [cited 2024 Oct. 5];13(4):18-22. Available from: https://pjp.pps.org.pk/index.php/PJP/article/view/282