THE PROTECTIVE EFFECT OF TURMERIC RHIZOMES EXTRACT FROM HEPATOTOXICITY AND NEPHROTOXICITY INDUCED BY INDOMETHACIN
DOI:
https://doi.org/10.22159/ajpcr.2026v19i1.56542Keywords:
Hepatotoxicity, Nephrotoxicity, Indomethacin, TurmericAbstract
Objective: This study was conducted to investigate the effect of the ethanolic extract of turmeric rhizomes (Curcuma longa)on reducing hepatotoxicity and nephrotoxicity induced by Indomethacin in male white mice (the Balb-c strain), and to examine its potential in mitigating the side effects of this drug.
Methods: Mice were randomly divided into four groups (10 mice/group). The first group (G1) was dosed with dimethyl sulfoxide (DMSO) 10%. The second group (G2) was given only turmeric rhizome extract dissolved in DMSO 10%. The third group (G3) was dosed with one dosage (166 mg/kg) of Indomethacin drug for 6 h. The fourth group (G4) was dosed with a dosage (300 mg/kg) of turmeric rhizome extract for 30 days then was dosed a dosage (166 mg/kg) of Indomethacin after 6 h. Serum levels of creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured, and a histological study of the livers and kidneys was performed.
Results: Results showed a significant increase in liver enzymes (AST and ALT), LDH, and creatinine in G3 (477 U/L, 942 U/L, 5323 U/L, and 1.37 mg/dl, respectively), compared to G1 (41, 48, 455, and 0.63, respectively), while observed reduction in those biochemical parameters in G4 (63, 102, 1625, and 0.82, respectively). Results also showed the ability of turmeric rhizome extract (300 mg/kg) to decrease the pathological changes induced by indomethacin in the liver and kidney, as severe degenerative changes, Necrotic single cells, and vascular congestion.
Conclusion: This study showed the important role of the ethanolic extract of turmeric rhizome in keeping the tissue structure of each liver and kidney safe from oxidative stress established by Indomethacin.
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References
1. Kleiner DE, Chalasani NP, Lee WM, Fontana RJ, Bonkovsky HL, Watkins PB, et al. Hepatic histological findings in suspected drug-induced liver injury: Systematic evaluation and clinical associations. Hepatology. 2014;59(2):661-70. doi: 10.1002/hep.26709, PMID 24037963
2. Si YC, Jiang Y, Yu HS, Yu CS. Kidney-based in vivo model for drug-induced nephrotoxicity testing. Sci Rep. 2020;10(1):1-12.
3. Perazella MA, Rosner MH. Drug-induced acute kidney injury. Clin J Am Soc Nephrol. 2022;17(8):1220-33. doi: 10.2215/CJN.11290821, PMID 35273009
4. Hassan S, Abo Elwafa S, El-Baz M, Hussein H, Gobba N. The potential protective effect of strawberry extract against indomethacin-induced liver toxicity and gastric ulceration in rats: Biochemical, histopathological and genetic studies. Int J Pharm Sci Res. 2021;12(6):3120-33.
5. Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol. 2020;180:114147. doi: 10.1016/j. bcp.2020.114147, PMID 32653589
6. Azwanida N. A review on the extraction methods use in medicinal plants, principle, strength and limitation. Med Aromat Plants 2015;4:3.
7. Orhan I. Biotechnological Production of Plant Secondary Metabolites. Sharjah: Bentham Science Publishers; 2012. p. 252.
8. Abdel-Shafy A, Alanazi S, Gabr A, Allam H, Abou-Zeina R, Masoud H, et al. Efficacy and safety of ethanol Curcuma longa extract as a treatment for sand Tampan ticks in a rabbit model. Vet World. 2020;13(4):812-20.
9. Wu H, Liu Z, Zhang Y, Gao B, Li Y, He X, et al. Chemical composition of turmeric (Curcuma longa L.) ethanol extract and its antimicrobial activities and free radical scavenging capacities. Foods. 2024;13(10):1550. doi: 10.3390/foods13101550, PMID 38790848
10. Essa R, El Sadek AM, Baset ME, Rawash MA, Sami DG, Badawy MT, et al. Effects of turmeric (Curcuma longa) Extract in streptozocin-induced diabetic model. J Food Biochem. 2019;43(9):e12988. doi: 10.1111/jfbc.12988, PMID 31489664
11. Yuliani G, Partadiredja S, Mustofa. The neuroprotective effects of an ethanolic turmeric (Curcuma longa L.) extract against trimethyltin-induced oxidative stress in rats. Nutr Neurosci. 2019;22(11):797-804.
12. Ghiamati Yazdi F, Soleimanian-Zad S, Van den Worm E, Folkerts G. Turmeric extract: Potential use as a prebiotic and anti-inflammatory compound? Plant Foods Hum Nutr. 2019;74(3):293-9. doi: 10.1007/ s11130-019-00733-x, PMID 31098880
13. Shakeri F, Soukhtanloo M, Boskabady MH. The effect of hydro-ethanolic extract of Curcuma longa rhizome and curcumin on total and differential WBC and serum oxidant, antioxidant biomarkers in rat model of asthma. Iran J Basic Med Sci. 2017;20(2):155-65. doi: 10.22038/ijbms.2017.8241, PMID 28293392
14. Dorcas MF, Gborieneomie SL, Onyije F. Histopathology and anticolon cancer effects of turmeric ethanolic extracts in Wistar Rats. ESJ. 2021;17(14):147-66.
15. Orona-Ortiz A, Medina-Torres L, Velázquez-Moyado JA, Pineda- Peña EA, Balderas-López JL, Bernad-Bernad MJ, et al. Mucoadhesive effect of Curcuma longa extract and curcumin decreases the ranitidine effect, but not bismuth subsalicylate on ethanol-induced ulcer model. Sci Rep. 2019;9(1):16622. doi: 10.1038/s41598-019-53089-2, PMID 31719599
16. Erdtman G. The acetolysis method-a revised description. Sven Bot Tidskr. 1960;54:561-4.
17. Wang L, Weller CL. Recent advances in extraction of nutraceuticals from plants. Trends Food Sci Technol. 2006;17(6):300-12. doi: 10.1016/j.tifs.2005.12.004
18. Taiwo O, Conteh V. The rodenticidal effect of indomethacin: Pathogenesis and pathology. Vet Arh. 2008;78(2):167-78.
19. Santoshkumar J, Manjunath S, Mariguddi P, Kalashetty D, Dass P, Manjunath C. Anti-diabetic effects of turmeric in alloxan induced diabetic rats. J Evol Med Dent Sci. 2013;2(11):1669-79. doi: 10.14260/ jemds/442
20. Bagheri SM, Zare-Mohazabieh F, Momeni-Asl H, Yadegari M, Mirjalili A, Anvari M. Antiulcer and hepatoprotective effects of aqueous extract of Plantago ovata seed on indomethacin-ulcerated rats. Biomed J. 2018;41(1):41-5. doi: 10.1016/j.bj.2018.01.001, PMID 29673551
21. Vernetti LA, Vogt A, Gough A, Taylor DL. Evolution of experimental models of the liver to predict human drug hepatotoxicity and efficacy. Clin Liver Dis. 2017;21(1):197-214. doi: 10.1016/j.cld.2016.08.013, PMID 27842772
22. Friedrich E, Akimova M, Huf A, Konstantinidis W, Papageorgiou D, Winkler K, et al. Drug-induced liver injury during antidepressant treatment: results of AMSP, a drug surveillance program. Int J Neuropsychopharmacol. 2016;19(4):1-9.
23. Gowda S, Desai PB, Hull VV, Math AA, Vernekar SN, Kulkarni SS. A review on laboratory liver function tests. Pan Afr Med J. 2009;3:17. PMID 21532726
24. Barnett LM, Cummings BS. Cellular and molecular mechanisms of kidney toxicity. Semin Nephrol. 2019;39(2):141-51. doi: 10.1016/j. semnephrol.2018.12.004, PMID 30827337
25. Modi S, Mody C, Patel G, Dudhatra H, Kumar M, Avale A. Toxic pathological overview of analgesic and anti-inflammatory drugs inanimals. J Appl Pharm Sci. 2012;2(1):149-57.
26. Hilal Ahmad M, Fatima M, Hossain MM, Mondal AC. Determination of potential oxidative damage, hepatotoxicity, and cytogenotoxicity in male Wistar rats: Role of indomethacin. J Biochem Mol Toxicol. 2018;32(12):e22226. doi: 10.1002/jbt.22226, PMID 30252991
27. Negi A, Mirza K. Nephroprotective and therapeutic potential of traditional medicinal plants in renal diseases. J Drug Res Ayurvedic Sci. 2020;5:177-85.
28. Sarhat S, Wadee E, Sedeeq T, Sarhat B. Biochemical and histological evaluation of indomethacin-induced hepatotoxicity in rats. Sci Transl Med. 2019;12(109) 23-35.
29. Eljafari A, Dugani M, Treesh A, Musa S. The effect of tamoxifen on indomethacin induced hepato-nephrotoxicity in rats. J Clin Exp Pharmacol. 2020;10(269):1-5.
30. Hassan N, Ibrahim G, Hjouz R, Issa H. Identification of bioactive components and its biological activities of ethanol extracts of turmeric ana Aloe vera -a GC-MS study. 2023;54:(2):163-78.
31. Stephanie O, David T, Farombi EO. Thymol reduces hepatorenal oxidative stress, inflammation and caspase-3#xd; activation in rats exposed to indomethacin. EJBAS. Egypt J Basic Appl Sci. 2022;9(1):136-50. doi: 10.1080/2314808X.2022.2050114
32. Al-Mayali ZK, Jaffat HS, Mohammed JA. Effect of the indomethacin drug on kidney histology in male albino rats. Int J Pharm Qual Assur. 2019;10(3):162-7. doi: 10.25258/ijpqa.10.3.9
33. Wadi E, Sarhat S, Sedeeq T, Sarhat B. Some biochemical and histological changes of rats kidneys (males) post indomethacin administration. Sci Adv Res. part I; 2020;15(15):1-33.
34. Basivireddy J, Jacob M, Pulimood K, Balasubramanian KA. Indomethacin-induced renal damage: Role of oxygen free radicals. Biochem Pharmacol. 2004;67(3):587-99. doi: 10.1016/j. bcp.2003.09.023, PMID 15037210
35. Türkyılmaz İ, Yanardağ R. Antioxidants prevent indomethacin-induced oxidative damage in tongue tissues of rats. Istanb J Pharm. 2023;53(1):73-9. doi: 10.26650/IstanbulJPharm.2023.98695
36. Nagano Y, Matsui H, Muramatsu M, Shimokawa O, Takeshi A, Yanaka A, et al. Rebamipide significantly inhibits indomethacin-induced mitochondrial damage, lipid peroxidation, and apoptosis in gastric epithelial RGM-1 cells. Dig Dis Sci. 2005;50 Suppl 1:S76-83. doi: 10.1007/s10620-005-2810-7, PMID 16184425
37. Wang K. Molecular mechanisms of hepatic apoptosis. Cell Death Dis. 2014;5(1):e996. doi: 10.1038/cddis.2013.499, PMID 24434519
38. Scholz M, Blobaum AL, Marnett LJ, Hey-Hawkins E. Ortho-carbaborane derivatives of indomethacin as cyclooxygenase (COX)- 2 selective inhibitors. Bioorg Med Chem. 2012;20(15):4830-7. doi: 10.1016/j.bmc.2012.05.063, PMID 22748709
39. Kotoh K, Kohjima KM, Tanaka M, Miyazaki M, Nakamura M, Enjoji K, et al. R. Lactate dehydrogenase production in hepatocytes is increased at an early stage of acute liver failure. Exp Ther Med. 2011;19(2):195-9.
40. Sedeeq B. Histological and biochemical changes of rats kidneys post indomethacin in administration. J Popul Ther Clin Pharmacol. 2023;30(3):e426-32.
41. David AO, Olatunde TF. Manganese inhibits indomethacin-induced hepatorenal oxidative stress in Wistar rats. JBCRR. 2020;29(9):79-90.
42. Khan S, Yusufi FN, Yusufi AN. Comparative effect of indomethacin (IndoM) on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in the kidney, small intestine and liver of rats. Toxicol Rep. 2019;6:389-94. doi: 10.1016/j.toxrep.2019.04.010, PMID 31080746
43. Bolat M, Selcuk D. Stereological and biochemical evaluation of diclofenac-induced acute nephrotoxicity in rats. Rev Méd Vét. 2013;6(6):290-4.
44. Nagappan AS, Varghese J, Pranesh GT, Jeyaseelan V, Jacob M. Indomethacin inhibits activation of endothelial nitric oxide synthase in the rat kidney: Possible role of this effect in the pathogenesis of indomethacin-induced renal damage. Chem-Biol Interact. 2014;221:77-87. doi: 10.1016/j.cbi.2014.07.014, PMID 25110317
45. Islam Shawon S, Nargis Reyda R, Qais N. Medicinal herbs and their metabolites with biological potential to protect and combat liver toxicity and its disorders: A review. Heliyon. 2024;10(3):e25340 doi: 10.1016/j.heliyon.2024.e25340, PMID 38356556
46. Wu JN, Wang W, Li B, Wei Z, Wei J, Jin B, et al. 7-hydroxycoumarin protects against cisplatin-induced acute kidney injury by inhibiting necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation. Phytomedicine. 2020;69:1-33.
47. Laasya S, Thakur TP, Poduri G, Joshi R. Current insights toward kidney injury: decrypting the dual role and mechanism involved of herbal drugs in inducing kidney injury and its treatment. Curr Res Biotechnol. 2020;2:161-75.
48. Ahama E, Igben VJ, Ubogu J, Ifechukwude IO, Nwabuoku US, Okwuribo P, et al. Potential nephrotoxic sequel of the kidney following exposure to turmeric extract in adult Wistar rats. J Coll Med Sci Nepal. 2023;19(4):482-8. doi: 10.3126/jcmsn.v19i4.48718
49. Nisar M, Iqbal T, Raza A. Turmeric: A promising spice for phytochemical and antimicrobial activities. Am Eurasian J Agric Environ Sci. 2015;15(7):1278-88.
50. Sharifi-Rad J, Rayess YE, Rizk AA, Sadaka C, Zgheib R, Zam W, et al. Turmeric and its major compound curcumin on health: Bioactive effects and safety profiles for food, pharmaceutical, biotechnological and medicinal applications. Front Pharmacol. 2020;11:01021. doi: 10.3389/fphar.2020.01021, PMID 33041781
51. Aggarwal BB, Yuan W, Li S, Gupta SC. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Mol Nutr Food Res. 2013;57(9):1529-42. doi: 10.1002/mnfr.201200838, PMID 23847105
52. Ibáñez M, Blázquez M. Curcuma longa L. rhizome essential oil from extraction to its Agri-food applications. A review. Plants (Basel). 2021;10:44:1-31.
53. Jayathilake M, Jayasinghe A, Walpita J. Development of ginger, turmeric oleoresins and pomegranate peel extracts incorporated pasteurized milk with pharmacologically important active compounds. Appl Food Res. 2022;2:100063.
54. Cheng JJ, Yang NB, Wu L, Lin JL, Dai GX, Zhu JY. Effects of zedoary turmeric oil on P450 activities in rats with liver cirrhosis induced by thioacetamide. Int J Clin Exp Pathol. 2014;7(11):7854-62. PMID 25550825
55. Surendran S, Qassadi F, Surendran G, Lilley D, Heinrich M. Myrcene-what are the potential health benefits of this flavouring and aroma agent? Front Nutr. 2021;8:699666. doi: 10.3389/fnut.2021.699666, PMID 34350208
56. Sarfraz H, Ullah M, Iqbal G, Shaheen R, Albalawi F, Alatawi M, et al. Antidiabetic effect of black pepper, turmeric, and ajwa date pulp, seed, and their mixtures as antioxidants in alloxan diabetic rats. J Anim Feed Sci. 2024;202(33):28-46.
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