ESTABLISHMENT OF NOVEL URINARY KIDNEY DISEASE NEW BIOMARKERS AND THERAPEUTIC EFFECT OF METHANOL FRACTION OF TERMINALIA ARJUNA ON ACETAMINOPHEN INDUCED KIDNEY DISEASE IN RATS
Objective: There were main two objectives, first was the identification of best biomarkers for early screening of kidney diseases whether plasma urea and creatinine or novel urinary low molecular weight protein biomarkers Interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and cystatin-C. Second was the therapeutic efficacy of methanol fraction of Terminalia arjuna (MFTA) on urinary novel biomarkers.
Methods: A total of 35 adult male rats were divided into three Groups (n=5), Group 1 was fed normal food, Group 2, normal food with administration of acetaminophen (APAP) for 5 days, 10 days, and 15 days, and Group 3, normal food with administration of APAP and coadministration of MFTA for 5 days, 10 days, and 15 days. All rats were sacrificed at 15th day of the experiment.
Results: Results showed 5 days, 10 days, and 15 days administrations of APAP increased novel urinary biomarkers as IL-18, KIM-1 near two-folds and cystatin-C near six-folds increased than old biomarkers plasma urea and plasma creatinine. Administration of APAP with coadministration of MFTA represented the protective effect by decreasing old and new novel biomarkers with superoxide dismutase and catalase but malondialdehyde level increased. Sodium dodecyle sulphate-polyacrylamide gel electrophoresis showed new low molecular weight urinary protein bands in APAP administration rats, the protective effect of MFTA presents no band at this molecular level as normal rats.
Conclusion: MFTA is the most potent nephroprotective agent, and urinary low molecular proteins are the best thing diagnostic tools for early detection of kidney disease over common plasma urea and creatinine.
2. Das K, Roy S, Mandal S, Pradhan S, Debnath S, Ghosh D, et al. Renal protection by isolated phytocompounds from TA bark fraction on dehydration induced uremia, oxidative stress and kidney disease rats. Int J Rec Sci Res 2016;7:13787-95.
3. Das K, Ghosh D, Nandi DK. Reno-protective effect of bark extract of TA on dehydration induced uremia of rat. Int J Physiol Allied Sci 2011;65:43-58.
4. Roy S, Das K, Mandal S, Pradhan S, Patra A, Nandi DK. Crude root extract of Asparagus racemosus ameliorates acetaminophen induced uremic rats. Int J Pharm Sci Res 2013;4:3004-12.
5. Das K, Samanta TT, Samanta P, Nandi DK. Effect of extract of Withania somnifera on dehydration-induced oxidative stress-related uremia in male rats. Saudi J Kidney Dis Transpl 2010;21:75-80.
6. Pradhan S, Mandal S, Roy S, Mandal A, Das K, Nandi DK. Attenuation of uremia by orally feedingalpha – Lipoic acid on acetaminophen induced uremic male rats. Saudi Pharm J 2013;21:187-92.
7. Mandal A, Nandi DK, Roy S, Das K, Mondal KC. In vivo assessment of bacteriotherapy on acetaminophen induced uremic rats. J Nephrol 2013a;26:228-36.
8. Roy S, Pradhan S, Das K, Mandal A, Mandal S, Patra A, et al. Acetaminophen induced kidney failure in rats: A dose response study. J Biol Sci 2015;15:187-93.
9. Das K, Chakraborty PP, Ghosh D, Nandi DK. Protective effect of aqueous extract of TA against dehydrating induced oxidative stress and uremia in male rat. Iran J Pharm Res 2010a;9:153-61.
10. Bonventre JV. Kidney injury molecule-1 (KIM-1): A urinary biomarker and much more. Nephrol Dial Transplant 2009;24:3265-8.
11. Liang XL, Liu SX, Chen YH, Yan LJ, Li H, Xuan HJ, et al. Combination of urinary kidney injury molecule-1 and interleukin-18 as early biomarker for the diagnosis and progressive assessment of acute kidney injury following cardiopulmonary bypass surgery: A prospective nested case-control study. Biomarkers 2010;15:332-9.
12. Herget-Rosenthal S, Marggraf G, Hüsing J, Göring F, Pietruck F, Janssen O. Early detection of acute renal failure by serum cystatin C. Kidney Int 2004;66:1115-22.
13. Olfert ED, Cross BM, McWilliam AA, editors. Guide to the Care and Use of Experimental Animals. Ottawa, Canada: Canadian Council on Animal Care; 1993. p. 82-93.
14. Zhou H, Yuen PS, Pisitkun T, Gonzales PA, Yasuda H, Dear JW, et al. Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery. Kidney Int 2006;69:1471-6.
15. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
16. Marklund S, Marklund G. Involvement of superoxide anion radical in auto oxidation of pyrogallol and a convenient assay of superoxide dismutase. Eur J Biochem 1974;47:469-74.
17. Dinarello CA, Novick D, Puren AJ, Fantuzzi G, Shapiro L, Mühl H, et al. Overview of interleukin-18: More than an interferon-gamma inducing factor. J Leukoc Biol 1998;63:658-64.
18. Ren H, Zhou X, Dai D, Liu X, Wang L, Zhou Y, et al. Assessment of urinary kidney injury molecule-1 and interleukin-18 in the early post-burn period to predict acute kidney injury for various degrees of burn injury. BMC Nephrol 2015;16:142.
19. Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney injury molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury. Kidney Int 2002;62:237-44.
20. Jiang R, Xu C, Zhou X, Wang T, Yao G. Detection of cystatin C biomarker for clinical measurement of renal disease by developed ELISA diagnostic kits. J Transl Med 2014;12:205.
21. Dunn MJ. Gel Electrophoresis PROTEIN. Oxford: BIOS Scientific Publishers Ltd.;1993.
22. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970;227:680-5.
23. Palani S, Raja S, Kumar RP, Jayakumar S, Kumar BS. Therapeutic efficacy of Pimpinella tirupatiensis (Apiaceae) on acetaminophen induced nephrotoxicity and oxidative stress in male albino rats. Int J Pharm Tech Res 2009;1:925-34.
24. Sokal RR, Rohle FJ. Introduction to analysis of variance. In: Biometry. New York; W H Freeman and Company: 1997. p. 179-206.
25. Sirota JC, Klawitter J, Edelstein CL. Biomarkers of acute kidney injury. J Bras Nefrol 2013;35:229-36.
26. Parikh CR, Jani A, Melnikov VY, Faubel S, Edelstein CL. Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis 2004;43:405-14.
27. Lin X, Yuan J, Zhao Y, Zha Y. Urine interleukin-18 in prediction of acute kidney injury: A systemic review and meta-analysis. J Nephrol 2015;28:7-16.
28. de Geus HR, Betjes MG, Bakker J. Biomarkers for the prediction of acute kidney injury: A narrative review on current status and future challenges. Clin Kidney J 2012;5:102-8.
29. Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem 1998;273:4135-42.
30. Gong R, Rifai A, Dworkin LD. Anti-inflammatory effect of hepatocyte growth factor in chronic kidney disease: Targeting the inflamed vascular endothelium. J Am Soc Nephrol 2006;17:2464-73.
31. Abhirama BR, Shanmuga Sundaram R, Raju A. Amelioration of gentamicin-induced renal damage in rats by ethanol extract of the whole plant Biophytum sensitivum (Linn.) Dc. Int J Pharm Pharm Sci 2018;10:130-5.
32. Cirevalli P, Nimmanapalli HD, Parlapalli LK, Nuthalapati LS, Kuttiappan A, Bhotla SK. Pill burden, drug class distribution and financial burden for buying medicines in different modalities of chronic kidney disease patients: Cross-sectional study. Int J Pharm Pharm Sci 2018;10:165-70.
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