Meghana Bhat M., Vinutha R Bhat, Amrita Parida, Sushma R K, Basavaraj Poojar, Manju V.
Meghana Bhat M.1, Vinutha R Bhat1, Amrita Parida2*, Sushma R K3, Basavaraj Poojar4, Manju V.5
1Department of Biochemistry, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka -576104. India.
2Department of Pharmacology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka -576104. India.
3Department of Anatomy, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka -576104. India.
4Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka -575001. India.
5Department of Paediatrics, Dr. TMA Pai Rotary Hospital, Karkala, Manipal Academy of Higher Education, Manipal, Karnataka -575001. India.
Volume - 16,
Issue - 5,
Year - 2023
Gentamicin, an aminoglycoside, is a commonly given antibiotic in cases of severe infections caused by gram-negative bacteria. Though being a very effective drug against gram negative organisms, its potential to cause nephrotoxicity restricts its use. The current study shows the effect of vortioxetine in gentamicin induced nephrotoxicity. Twenty-four female wistar albino rats weighing 180-220g, 8-10-week old were selected for the study and randomly assigned to 4 groups. Group 1: normal control, received only distilled water; Group 2: gentamicin 80mg/kg b.w. for 8 days; Group 3: vortioxetine 10mg/kg b.w., pre-treatment for 5 days followed by gentamicin 80mg/kg b.w. for 8 days; Group 4: vortioxetine 20mg/kg b.w., pre-treatment for 5 days followed by gentamicin 80mg/kg b.w. for 8 days. At the end of the experiment, serum urea, serum creatinine, tissue malondialdehyde (MDA) and tissue glutathione (GSH) were estimated and histological examination of kidneys was performed. One-way ANOVA and post hoc Tukey’s tests were performed. Serum urea and serum creatinine and tissue MDA increased markedly in the gentamicin group with a p-value < 0.001, and tissue GSH reduced significantly (p < 0.001). Treatment with vortioxetine had ameliorated gentamicin induced kidney damage. This was corroborated by reduced serum urea, serum creatinine, and MDA levels (p< 0.001), and elevated GSH levels (p< 0.001). In conclusion, vortioxetine has protective effective on gentamicin-induced nephrotoxicity in rats.
Cite this article:
Meghana Bhat M., Vinutha R Bhat, Amrita Parida, Sushma R K, Basavaraj Poojar, Manju V. Evaluation of Nephroprotective Effect of Vortioxetine in Gentamicin-Induced Renotoxicity in Wistar rats. Research Journal of Pharmacy and Technology 2023; 16(5):2223-8. doi: 10.52711/0974-360X.2023.00365
Meghana Bhat M., Vinutha R Bhat, Amrita Parida, Sushma R K, Basavaraj Poojar, Manju V. Evaluation of Nephroprotective Effect of Vortioxetine in Gentamicin-Induced Renotoxicity in Wistar rats. Research Journal of Pharmacy and Technology 2023; 16(5):2223-8. doi: 10.52711/0974-360X.2023.00365 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-5-24
1. Randjelovic P, Veljkovic S, Stojiljkovic N, Sokolovic D, Ilic I. Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI J. 2017 Mar 24;16:388-399. doi: 10.17179/excli2017-165. 2. Udupa V, Prakash V. Gentamicin induced acute renal damage and its evaluation using urinary biomarkers in rats. Toxicol Rep. 2018 Nov 30;6:91-99. doi: 10.1016/j.toxrep.2018.11.015.
2. Basnakian AG, Kaushal GP, Shah S V. Apoptotic pathways of oxidative damage to renal tubular epithelial cells. Antioxidants Redox Signal. 2002;4(6):915–24.
3. Famurewa AC, Maduagwuna EK, Folawiyo AM, Besong EE, Eteudo AN, Famurewa OA, et al. Antioxidant, anti-inflammatory, and antiapoptotic effects of virgin coconut oil against antibiotic drug gentamicin-induced nephrotoxicity via the suppression of oxidative stress and modulation of iNOS/NF-ĸB/caspase-3 signaling pathway in Wistar rats. J Food Biochem. 2020;44(1):1–10.
4. Ateşşahin A, Yilmaz S, Karahan I, Pirinçci I, Taşdemir B. The effects of vitamin E and selenium on cypermethrin-induced oxidative stress in rats ahmet. Turkish J Vet Anim Sci. 2005;29(2):385–91.
5. Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Di Paola R, Britti D, et al. A role for superoxide in gentamicin-mediated nephropathy in rats. Eur J Pharmacol. 2002;450(1):67–76.
6. Apaydin Yildirim B, Kordali S, Terim Kapakin KA, Yildirim F, Aktas Senocak E, Altun S. Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats. J Zhejiang Univ Sci B. 2017;18(6):501-511. doi:10.1631/jzus.B1500291
7. Chen G, Højer AM, Areberg J, Nomikos G. Vortioxetine: Clinical Pharmacokinetics and Drug Interactions. Clin Pharmacokinet. 2018;57(6):673-686. doi:10.1007/s40262-017-0612-7
8. Talmon M, Rossi S, Pastore A, Cattaneo CI, Brunelleschi S, Fresu LG. Vortioxetine exerts anti-inflammatory and immunomodulatory effects on human monocytes/macrophages. Br J Pharmacol. 2018;175(1):113–24.
9. Stocks J, Dormandy TL. The Autoxidation of Human Red Cell Lipids Induced by Hydrogen Peroxide. Br J Haematol. 1971;20(1):95–111.
10. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70-7. doi: 10.1016/0003-9861(59)90090-6. PMID: 13650640.
11. Kuraeiad S, Kotepui M. Blood Lead Level and Renal Impairment among Adults: A Meta-Analysis. Int J Environ Res Public Health. 2021 Apr 15;18(8):4174. doi: 10.3390/ijerph18084174.
12. Doi, K., Nishida, O., Shigematsu, T. et al. The Japanese Clinical Practice Guideline for acute kidney injury 2016. j intensive care 6, 48 (2018). https://doi.org/10.1186/s40560-018-0308-6
13. Bashan L, Bashan P, Seçilmis MA, Singirik E. Protective effect of L-arginine on gentamicin-induced nephrotoxicity in rats. Indian J Pharmacol. 2014;46(6):608–12.
14. Passey RB, Gillum RL, Fuller JB, Urry FM, Baron ML. Evaluation of three methods for the measurement of urea nitrogen in serum as used on six instruments. Am J Clin Pathol. 1980;73(3):362–8.
15. Wong HS, Chen JH, Leong PK, Leung HY, Chan WM, Ko KM. β-sitosterol protects against carbon tetrachloride hepatotoxicity but not gentamicin nephrotoxicity in rats via the induction of mitochondrial glutathione redox cycling. Molecules. 2014;19(11):17649-17662. doi:10.3390/molecules191117649
16. Ullah N, Khan MA, Khan T, Asif AH, Ahmad W. Mentha piperita in nephrotoxicity - A possible intervention to ameliorate renal derangements associated with Gentamicin. Indian J Pharmacol. 2014;46(2):166–70.
17. Randjelovic P, Veljkovic S, Stojiljkovic N, et al. Salicylic acid attenuates gentamicin-induced nephrotoxicity in rats. Scientific World Journal. 2012;2012:390613. doi:10.1100/2012/390613
18. Delanghe JR, Speeckaert MM. Creatinine determination according to Jaffe-what does it stand for?. NDT Plus. 2011;4(2):83-86. doi:10.1093/ndtplus/sfq211
19. El-Kashef DH, El-Kenawi AE, Suddek GM, Salem HA. Protective effect of allicin against gentamicin-induced nephrotoxicity in rats. Int Immunopharmacol. 2015 Dec;29(2):679-686. doi: 10.1016/j.intimp.2015.09.010
20. Veljković M, Pavlović DR, Stojiljković N, Ilić S, Petrović A, Jovanović I, Radenković M. Morphological and morphometric study of protective effect of green tea in gentamicin-induced nephrotoxicity in rats. Life Sci. 2016 Feb 15;147:85-91. doi: 10.1016/j.lfs.2016.01.035.
21. Seema Kashyap, Malti Sao, Harish Sharma, Amrendra Pratap Yadav, Mohan Lal Kori. Nephroprotective Effect of Luteolin against Gentamicin-induced Nephrotoxicity in Albino Rats. Res. J. Pharma. Dosage Forms and Tech.2019; 11(4):253-256
22. Nadira Noushida, Preethi J. Shenoy, Rashmi R. Rao, S. Teerthanath, Sudhishma. Nephroprotective activity of betulinic acid in gentamicin induced murine model of Renotoxicity. Research J. Pharm. and Tech 2020; 13(3):1391-1396.
23. Gyory1 AZ, Edwards KDG, Stewart JH, Whyte HM. Comprehensive one-day renal function testing in man. Journal of Clinical Pathology 1974;27:382-391.
24. Nitin M, Ifthekar S. Nephroprotective activity of Vigna mungo (Linn.) Hepper on gentamicin-induced renal damage in albino rats. Research J. Pharmacology and Pharmacodynamics. 2012; 4(5): 299-303.
25. Wen Y, Parikh CR. The aftermath of AKI: Recurrent AKI, acute kidney disease, and CKD progression. J Am Soc Nephrol. 2021;32(1):2–4.
26. Aarif Wani, Jasmine Chaudhary, Akash Jain. A Study to Evaluate the combined effect of cromolyn Sodium and Fenofibrate in Gentamicin induced Nephropathy. Research J. Pharm. and Tech. 2020; 13(7): 3215-3220.
27. Breshears MA, Confer AW. The Urinary System. Pathol Basis Vet Dis Expert Consult. 2017;617-681.e1.
28. Dileep Bharati, Swapnil Goyal, Anirbandeep Bose. Nephroprotective Activity of Dichloromethane Extract of Leaves of Alstonia scholaris Linn. in Gentamycin Induced Nephrotoxicity in Rats: Preventive Study. Research J. Pharm. and Tech. 2021; 14(2):1055-1058.
29. McKeever WP. Acute Renal Tubular Necrosis. Jama. 1967;200(2):174.
30. Nakhla J, de la Garza Ramos R, Bhashyam N, Kobets A, Nasser R, Echt M, Lang G, Navarro-Ramirez R, Jada A, Kinon M, Yassari R. The Impact of Kidney Disease on Acute Tubular Necrosis and Surgical Site Infection After Lumbar Fusion. World Neurosurg. 2017 Sep;105:498-502. doi: 10.1016/j.wneu.2017.05.088.