Role of cineole in alleviation of acute kidney injury and renal function recovery following gentamicin administration in rats

Document Type : Original Article

Authors

1 azi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran

2 Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran

3 Department of Clinical Biochemistry, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran

4 Department of Anatomy, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran

5 Department of Medical Laboratory Sciences, School of Paramedical Sciences, Dezful University of Medical Sciences, Dezful, Iran

6 Lorestan Agricultural and Natural Resources Research and Education Center, Department of Animal Science, Khorramabad, Iran

7 Medical Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

Abstract

Objective(s): Gentamicin leads to kidney failure by producing free radicals and inflammation in renal tissue. Cineole as a terpenoid has antioxidant properties. Antioxidants can play an effective role in preserving the oxidant-antioxidant balance. Hence, this study investigated the effects of cineole on acute kidney injury (AKI) and renal function recovery following gentamicin administration in rats.
Materials and Methods: 36 male Wistar rats were randomly divided into 6 equal groups; healthy control, gentamicin, DMSO carriers, cineole 50, cineole 100, and vitamin E. After 12 days of treatment, the animals were anesthetized with ketamine and xylazine. Serum and kidney samples were taken for biochemical and gene expression experiments.
Results: Cineole 50 and 100 groups increased the levels of serum glutathione (GSH) (<0.05), kidney and serum glutathione peroxidase (GPX) (<0.001), kidney catalase (CAT) (<0.001), serum nitric oxide (NO) (<0.001), and the GPX gene (<0.05) compared with the gentamicin group. These treatment groups had decreased levels of kidney malondialdehyde (MDA) (<0.001), serum creatinine (<0.001), urine protein, and the Interleukin 6 (IL-6) gene (<0.05) compared with the gentamicin group. Cineole 50 increased the serum MDA (<0.001), urea, and CAT gene (>0.05) and decreased the kidney GSH (<0.05) and the tumor necrosis factor-alpha (TNF-α) gene (<0.05). Cineole 100 increased the kidney GSH (<0.05) and decreased the serum MDA (<0.001), urea, CAT gene (>0.05), and TNF-α gene (>0.05) compared with the gentamicin group. Improvement in histological alterations was displayed in cineole groups compared with the gentamicin group.
Conclusion: Cineole can reduce kidney damage caused by nephrotoxicity following gentamicin consumption through its antioxidant and anti-inflammatory properties. 

Keywords

References

1. Hussien NR, Al-Kuraishy HM, Al-Gareeb AI. Berberine and Pentoxifylline: A novel combination in amelioration of acute kidney injury. J Pak Med Assoc 2019;69:98-97.
2. Eslamifar Z, Moridnia A, Sabbagh S, Ghaffaripour R, Jafaripour L, Behzadifard M. Ameliorative effects of gallic acid on cisplatin-induced nephrotoxicity in rat variations of biochemistry, histopathology, and gene expression. Biomed Res Int 2021;2021:2195238.
3. Alkuraishy HM, Al-Gareeb AI, Al-Naimi MS. Pomegranate protects renal proximal tubules during gentamicin induced-nephrotoxicity in rats. J Contemp Med Sci 2019;5:35-40.
4. Martinez-Salgado C, López-Hernández FJ, López-Novoa JM. Glomerular nephrotoxicity of aminoglycosides. Toxicol Appl Pharmacol 2007;223:86-98.
5. Al-Kuraishy HM, Al-Gareeb AI, Al-Maiahy TJ. Concept and connotation of oxidative stress in preeclampsia. J Lab physicians 2018;10:276-282.
6. Al-Kuraishy HM, Al-Gareeb AI, Al-Nami MS. Irbesartan attenuates gentamicin-induced nephrotoxicity in rats through modulation of oxidative stress and endogenous antioxidant capacity. Int J Prev Med 2020;11:16.
7. Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity. Kidney Int 2012;79:1-23.
8. Balakumar P, Rohilla A, Thangathirupathi A. Gentamicin-induced nephrotoxicity: Do we have a promising therapeutic approach to blunt it? Pharmacol Res 2010;62:179-186.
9. Erseckin V, Mert H, İrak K, Yildirim S, Mert N. Nephroprotective effect of ferulic acid on gentamicin-induced nephrotoxicity in female rats. Drug chem Toxicol 2022;45:663-669.
10. Yu S-Y, Chiu J-H, Yang S-D, Yu H-Y, Hsieh C-C, Chen P-J, et al. Preconditioned hyperbaric oxygenation protects the liver against ischemia-reperfusion injury in rats. J Surg Res 2005;128:28-36.
11. Naserzadeh R, Jafaripour L, Eslamifar Z, Alizamani E, Nouryazdan N, Ahmadvand H. The effect of receiving l-glutamine on the reduction of renal tissue damages and renal function recovery following gentamicin-induced nephrotoxicity in rats. J Babol Univ Med Sci 2021;23:267-274.
12. Valibeik A, Naderi N, Amini A, Tavakoli Dastjerd N, Rahimi Monfared S, Jafaripour L, et al. Effect of camphor on biochemical factors and gene expression of antioxidant enzymes, inflammatory and apoptotic factors against gentamicin-induced nephrotoxicity in rats. J Renal Inj Prev 2021;10:e21.
13. Santos F, Rao V. Antiinflammatory and antinociceptive effects of 1, 8‐cineole a terpenoid oxide present in many plant essential oils. Phytother Res 2000;14:240-244.
14. Santos F, Silva R, Campos A, De Araujo R, Júnior RL, Rao V. 1, 8-cineole (eucalyptol), a monoterpene oxide attenuates the colonic damage in rats on acute TNBS-colitis. Food Chem Toxicol 2004;42:579-584.
15. Jouad H, Maghrani M, Hassani RAE, Eddouks M. Hypoglycemic activity of aqueous extract of Eucalyptus globulus in normal and streptozotocin-induced diabetic rats. J Herbs Spices Med Plants 2004;10:19-28.
16. Lahlou S, Figueiredo AF, Magalhães PJC, Leal-Cardoso JH. Cardiovascular effects of 1, 8-cineole, a terpenoid oxide present in many plant essential oils, in normotensive rats. Can J Physiol  Pharmacol 2002;80:1125-1131.
17. Yarijani ZM, Najafi H, Madani SH. Protective effect of crocin on gentamicin-induced nephrotoxicity in rats. Iran J Basic Med Sci 2016;19:337-343.
18. Ciftci O, Ozdemir I, Tanyildizi S, Yildiz S, Oguzturk H. Antioxidative effects of curcumin, β-myrcene and 1, 8-cineole against 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in rats liver. Toxicol Ind Health 2011;27:447-453.
19. Ademuyiwa O, Ngaha E, Ubah F. Vitamin E and selenium in gentamicin nephrotoxicity. Hum Exp Toxicol 1990;9:281-288.
20. Zheng X-b, Zhang Y-l, Li Q, Liu Y-g, Wang X-d, Yang B-l, et al. Effects of 1, 8-cineole on neuropathic pain mediated by P2X2 receptor in the spinal cord dorsal horn. Sci Rep 2019;9:1-8.
21. Abd-Elhakim YM, Abdel-Motal SM, Malhat SM, Mostafa HI, Ibrahim WM, Beheiry RR, et al. Curcumin attenuates gentamicin and sodium salicylate ototoxic effects by modulating the nuclear factor-kappaB and apoptotic pathways in rats. Environ Sci  Pollut Res 2022;29:89954-89968.
22. Kruger N. The Bradford method for protein quantitation, Basic Protein Pept. Protoc; 1994.
23. Aebi H. [13] Catalase in vitro.  Methods in enzymology. 105: Elsevier; 1984. p. 121-6.
24. Rotruck J, Pope A, Ganther H, Swanson A, Hafeman D, Hoekstra W. Selenium: Biochemical role as a component of glutathione peroxidase. Nutr Rev 1980;38:280-283.
25. Coneski PN, Schoenfisch MH. Nitric oxide release: Part III. Measurement and reporting. Chem Soc Rev 2012;41:3753-3758.
26. Rio DC, Ares M, Hannon GJ, Nilsen TW. Purification of RNA using TRIzol (TRI reagent). Cold Spring Harb Protoc 2010;2010:pdb. prot5439.
27. Caramelo C, Espinosa G, Manzarbeitia F, Cernadas M, Tejerizo GPr, Tan D, et al. Role of endothelium-related mechanisms in the pathophysiology of renal ischemia/reperfusion in normal rabbits. Circ Res 1996;79:1031-1038.
28. Randjelovic P, Veljkovic S, Stojiljkovic N, Sokolovic D, Ilic I. Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI J 2017;16:388-399.
29. Ungur RA, Borda IM, Codea RA, Ciortea VM, Năsui BA, Muste S, et al. A flavonoid-rich extract of sambucus nigra l. reduced lipid peroxidation in a rat experimental model of gentamicin nephrotoxicity. Materials 2022;15:772.
30. Al-Kuraishy HM, Al-Gareeb AI, Al-Naimi MS. Renoprotective effect of irbesartan in a rat model of gentamicin-induced nephrotoxicity: Role of oxidative stress. J Lab Physicians 2019;11:200-205.
31. Ince S, Kucukkurt I, Demirel HH, Arslan-Acaroz D, Varol N. Boron, a trace mineral, alleviates gentamicin-induced nephrotoxicity in rats. Biol Trace Elem Res 2020;195:515-524.
32. Polat A, Parlakpinar H, Tasdemir S, Colak C, Vardi N, Ucar M, et al. Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats. Acta Histochem 2006;108:365-371.
33. Li C, Liu J, Saavedra JE, Keefer LK, Waalkes MP. The nitric oxide donor, V-PYRRO/NO, protects against acetaminophen-induced nephrotoxicity in mice. Toxicology 2003;189:173-180.
34. Soliman M, Alhaithloul HA, Hakeem KR, Alharbi BM, El-Esawi M, Elkelish A. Exogenous nitric oxide mitigates nickel-induced oxidative damage in eggplant by upregulating antioxidants, osmolyte metabolism, and glyoxalase systems. Plants 2019;8:562.
35. Moon HK, Kang P, Lee HS, Min SS, Seol GH. Effects of 1, 8-cineole on hypertension induced by chronic exposure to nicotine in rats. J Pharm Pharmacol 2014;66:688-693.
36. Al-Kuraishy HM, Al-Gareeb AI. Potential effects of pomegranate on lipid peroxidation and pro-inflammatory changes in daunorubicin-induced cardiotoxicity in rats. Int J Prev Med 2016;7:85.
37. Al-Kuraishy HM, Al-Gareeb AI, Al-Nami MS. Vinpocetine improves oxidative stress and pro-inflammatory mediators in acute kidney injury. Int J Prev Med 2019;10:142.
38. Jafaripour L, Naserzadeh R, Alizamani E, Mashhadi SMJ, Moghadam ER, Nouryazdan N, et al. Effects of rosmarinic acid on methotrexate-induced nephrotoxicity and hepatotoxicity in wistar rats. Indian J Nephrol 2021;31:218-224.
39. Jafaripour L, Naserzadeh R, Ahmadvand H, Hadipour Moradi F, Ghobadi K, Alizamani E, et al. Effects of L-glutamine on oxidative stress in gentamicin induced hepatotoxicity rats. J  Kerman Univ Med Sci 2019;26:36-42.
40. Rodenak-Kladniew B, Castro A, Stärkel P, Galle M, Crespo R. 1, 8-Cineole promotes G0/G1 cell cycle arrest and oxidative stress-induced senescence in HepG2 cells and sensitizes cells to anti-senescence drugs. Life sci 2020;243:117271.
41. Ryu S, Park H, Seol GH, Choi I-Y. 1, 8-Cineole ameliorates oxygen-glucose deprivation/reoxygenation-induced ischaemic injury by reducing oxidative stress in rat cortical neuron/glia. J Pharm Pharmacol 2014;66:1818-1826.
42. Dougnon G, Ito M. Inhalation administration of the bicyclic ethers 1, 8-and 1, 4-cineole prevent anxiety and depressive-like behaviours in mice. Molecules 2020;25:1884.
43. Juergens UR, Dethlefsen U, Steinkamp G, Gillissen A, Repges R, Vetter H. Anti-inflammatory activity of 1.8-cineol (eucalyptol) in bronchial asthma: A double-blind placebo-controlled trial. Respir Med 2003;97:250-256.
44. Cai Z-M, Peng J-Q, Chen Y, Tao L, Zhang Y-Y, Fu L-Y, et al. 1, 8-Cineole: A review of source, biological activities, and application. J Asian Nat Prod Res 2021;23:938-954.
45. Mahdavifard S, Nakhjavani M. 1, 8 cineole protects type 2 diabetic rats against diabetic nephropathy via inducing the activity of glyoxalase-I and lowering the level of transforming growth factor-1β. J Diabetes Metab Disord 2022;21:1-6.
46. Alatawi KA, Ravishankar D, Patra PH, Bye AP, Stainer AR, Patel K, et al. 1, 8-Cineole affects agonists-induced platelet activation, thrombus formation and haemostasis. Cells 2021;10:2616.
47. Xu J, Hu Z-Q, Wang C, Yin Z-Q, Wei Q, Zhou L-J, et al. Acute and subacute toxicity study of 1, 8-cineole in mice. Int J Clin Exp Pathol 2014;7:1495.
48. Farivar M, Hooshmandi Z, Setorki M, Amini S. Effect of Elettaria cardamomum essential oil and its main component (1, 8‐cineole) on brain damage caused by cerebral hypoperfusion by suppressing apoptosis and inflammation in rats. Iran Red Crescent Med J 2020;22:1-8.
Iranian Journal of Basic Medical Sciences
Volume 26, Issue 5
May 2023
Pages 504-510

Files

Share

How to cite

Statistics