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Protective role of citronellol on antioxidant enzymes and oxidative damage induced by gentamicin in experimental nephrotoxic rats

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Abstract

Background

Gentamicin leads to nephrotoxicity with increasing oxidative stress. In the present research the role of citronellol on oxidative damage induced by gentamicin in nephrotoxic rats was evaluated.

Methods and Results

Forty-twomale Wistar rats were randomly divided into seven equal groups; healthy control, gentamicin, DMSO, citronellol 50, citronellol 100, citronellol 200 and vitamin E. The animals were anesthetized after 12 days of treatment. Kidney and serum samples were received for biochemical, histological changes, and gene expression assessments. The levels of serum glutathione (GSH), serum and kidney glutathione peroxidase (GPX) and the expression of GPX gene against gentamicin group were increased in citronellol treatment groups. The levels of serum and kidney malondialdehyde (MDA), urine protein, serum creatinine and the gene expression of inflammatory factors including tumor necrosis factor-alpha (TNF-α) and Interleukin 6 (IL-6) against gentamicin group were decreased in these groups. Moreover, recuperation in histological alterations was shown in three groups receiving citronellol compared to the gentamicin group.

Conclusions

Citronellol with its antioxidant and anti-inflammatory properties can decrease kidney damage caused by nephrotoxicity induced by gentamicin.

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

References

  1. Zuk A, Bonventre JV (2016) Acute kidney injury. Annu Rev Med 67:293–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhi HJ, Li Y, Wang B, Cui XY, Zhang M, Hu ZJ (2020) Renal echography for predicting acute kidney injury in critically ill patients: a prospective observational study. Ren Fail 42(1):263–269

    Article  PubMed  PubMed Central  Google Scholar 

  3. Koratala A, Ronco C, Kazory A (2022) Multi-organ point-of-care ultrasound in acute kidney injury. Blood Purif 51(12):967–971

    Article  PubMed  Google Scholar 

  4. Okoro RN, Farate VT (2019) The use of nephrotoxic drugs in patients with chronic kidney disease. Int J Clin Pharm 41:767–775

    Article  CAS  PubMed  Google Scholar 

  5. Balakumar P, Rohilla A, Thangathirupathi A (2010) Gentamicin-induced nephrotoxicity: do we have a promising therapeutic approach to blunt it? Pharmacol Res 62(3):179–186

    Article  CAS  PubMed  Google Scholar 

  6. Valibeik A, Naderi N, Amini A, Dastjerd NT, Monfared SR, Jafaripour L et al (2020) 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. 10(3):e21

    Article  Google Scholar 

  7. Medić B, Stojanović M, Rovčanin B, Kekić D, Škodrić SR, Jovanović GB et al (2019) Pioglitazone attenuates kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats. Sci Rep 9(1):13689

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  8. Erseckin V, Mert H, İrak K, Yildirim S, Mert N (2022) Nephroprotective effect of ferulic acid on gentamicin-induced nephrotoxicity in female rats. Drug Chem Toxicol 45(2):663–669

    Article  CAS  PubMed  Google Scholar 

  9. Monfared SR, Valibeik A, Jafaripour L, Eslamifar Z, Veiskarami S, Ahmadvand H (2023) Role of cineole in alleviation of acute kidney injury and renal function recovery following gentamicin administration in rats. Iran J Basic Med Sci 26(5):504

    Google Scholar 

  10. Ahmadvand H, Babaeenezhad E, Nasri M, Jafaripour L, Khorramabadi RM (2018) Glutathione ameliorates liver markers, oxidative stress and inflammatory indices in rats with renal ischemia reperfusion injury. J Renal Inj Prev 8(2):91–97

    Article  Google Scholar 

  11. Babaeenezhad E, HadipourMoradi F, RahimiMonfared S, Fattahi MD, Nasri M, Amini A et al (2021) D-Limonene alleviates acute kidney injury following gentamicin administration in rats: role of NF-κB pathway, mitochondrial apoptosis, oxidative stress, and PCNA. Oxid Med Cell Longev 2021:1–16

    Article  Google Scholar 

  12. Georgiev T, Nikolova G, Dyakova V, Karamalakova Y, Georgieva E, Ananiev J et al (2023) Vitamin E and silymarin reduce oxidative tissue damage during gentamycin-induced nephrotoxicity. Pharmaceuticals 16(10):1365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mert H, Mert N, Yoruk M, Yoruk IH, Yildirim BA, Yilmaz HC (2022) Effect of coenzyme Q10 and vitamin E on gentamicin-induced nephrotoxicity in rats. GSC Biol Pharm Sci 21(2):033–040

    Article  CAS  Google Scholar 

  14. Janoti DS, Rana M, Rawat A (2014) Comparative antioxidant activity of essential oil of leaves of Citrus limettioides and Citrus pseudolimon of Nainital District. J Pharmacogn Phytochem 2(5):24–26

    Google Scholar 

  15. Santos MR, Moreira FV, Fraga BP, Souza DPd, Bonjardim LR, Quintans-Junior LJ (2011) Cardiovascular effects of monoterpenes: a review. Revista Brasileira de Farmacognosia. 21:764–771

    Article  CAS  Google Scholar 

  16. Munir S, Hafeez R, Younis W, Malik MNH, Munir MU, Manzoor W et al (2023) The protective effect of citronellol against doxorubicin-induced cardiotoxicity in rats. Biomedicines 11(10):2820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jayaraj RL, Azimullah S, Parekh KA, Ojha SK, Beiram R (2022) Effect of citronellol on oxidative stress, neuroinflammation and autophagy pathways in an in vivo model of Parkinson’s disease. Heliyon. 8(11):e11434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yarijani ZM, Najafi H, Madani SH (2016) Protective effect of crocin on gentamicin-induced nephrotoxicity in rats. Iran J Basic Med Sci 19(3):337

    PubMed  PubMed Central  Google Scholar 

  19. Hasanvand A, Tavafi M, Ahmadvand H, Tamjidipoor A. Effect of dimethyl sulfoxide in combat with gentamicin induced nephrotoxicity in rats. Journal of Nephropathology. 2020;9(3).

  20. Srinivasan S, Muruganathan U (2016) Antidiabetic efficacy of citronellol, a citrus monoterpene by ameliorating the hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Chem Biol Interact 250:38–46

    Article  CAS  PubMed  Google Scholar 

  21. Zheng X-b, Zhang Y-l, Li Q, Liu Y-g, Wang X-d, Yang B-l et al. (2019) Effects of 1, 8-cineole on neuropathic pain mediated by P2X2 receptor in the spinal cord dorsal horn. Sci Rep 9(1):7909

  22. Kruger NJ (2009) The Bradford method for protein quantitation. The protein protocols handbook. Human Press, pp 17–24

    Chapter  Google Scholar 

  23. Aebi H (1984) [13] Catalase in vitro. In: Methods in enzymology, vol. 105. Elsevier, pp. 121–126

  24. Coneski PN, Schoenfisch MH (2012) Nitric oxide release: part III. Measure Report Chem Soc Rev 41(10):3753–3758

    Article  CAS  PubMed  Google Scholar 

  25. Rio DC, Ares M, Hannon GJ, Nilsen TW (2010) Purification of RNA using TRIzol (TRI reagent). Cold Spring Harbor Protocols. 2010(6):pdb, prot5439

  26. Naserzadeh R, Jafaripour L, Eslamifar Z, Alizamani E, Nouryazdan N, Ahmadvand H (2021) 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 23(1)

  27. Nassan MA, Soliman MM, Aldhahrani A, Althobaiti F, Alkhedaide AQ (2021) Ameliorative impacts of Glycyrrhiza glabra root extract against nephrotoxicity induced by gentamicin in mice. Food Sci Nutr 9(7):3405–3413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Randjelovic P, Veljkovic S, Stojiljkovic N, Sokolovic D, Ilic I (2017) Gentamicin nephrotoxicity in animals: current knowledge and future perspectives. EXCLI J 16:388

    PubMed  PubMed Central  Google Scholar 

  29. Pedraza-Chaverri J, González-Orozco AE, Maldonado PD, Barrera D, Medina-Campos ON, Hernández-Pando R (2003) Diallyl disulfide ameliorates gentamicin-induced oxidative stress and nephropathy in rats. Eur J Pharmacol 473(1):71–78

    Article  CAS  PubMed  Google Scholar 

  30. Wimalawansa SJ (2008) Skeletal effects of nitric oxide: novel agent for osteoporosis. Principles of bone biology. Elsevier, pp 1273–1310

    Chapter  Google Scholar 

  31. Thomas DD, Ridnour LA, Isenberg JS, Flores-Santana W, Switzer CH, Donzelli S et al (2008) The chemical biology of nitric oxide: implications in cellular signaling. Free Radical Biol Med 45(1):18–31

    Article  CAS  Google Scholar 

  32. Kadkhodaee M, Khastar H, Faghihi M, Ghaznavi R, Zahmatkesh M (2005) Effects of co-supplementation of vitamins E and C on gentamicin-induced nephrotoxicity in rat. Exp Physiol 90(4):571–576

    Article  CAS  PubMed  Google Scholar 

  33. Sen S, Chakraborty R, Sridhar C, Reddy Y, De B (2010) Free radicals, antioxidants, diseases and phytomedicines: current status and future prospect. Int J Pharm Sci Rev Res 3(1):91–100

    CAS  Google Scholar 

  34. Masoudi R, Shahneh A, Asadzadeh N (2020) Improvement of Ram’s frozen sperm quality using glutathione antioxidant. Vet Res Biol Products 33(3):69–75

    Google Scholar 

  35. Masella R, Di Benedetto R, Varì R, Filesi C, Giovannini C (2005) Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem 16(10):577–586

    Article  CAS  PubMed  Google Scholar 

  36. Ciftci O, Ozdemir I, Tanyildizi S, Yildiz S, Oguzturk H (2011) 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 27(5):447–453

    Article  CAS  PubMed  Google Scholar 

  37. Tavafi M, Ahmadvand H, Toolabi P (2012) Inhibitory effect of olive leaf extract on gentamicin-induced nephrotoxicity in rats

  38. Jagdale AD, Kamble SP, Nalawade ML, Arvindekar AU (2015) Citronellol: A potential antioxidant and aldose reductase inhibitor from Cymbopogon citratus. Int J Pharm Pharm Sci 7:203–209

    CAS  Google Scholar 

  39. Yu W-N, Lai Y-J, Ma J-W, Ho C-T, Hung S-W, Chen Y-H et al (2019) Citronellol induces necroptosis of human lung cancer cells via TNF-α pathway and reactive oxygen species accumulation. In Vivo. 33(4):1193–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Widiyarti G, Megawati M, Hanafi M (2019) The potential use of geraniol esters from citronella oil as anticancer agents. Orient J Chem 35(3):987

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors greatly appreciate the assistance of the staff of the research laboratory, Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, for conducting this research.

Funding

Financial support for this research was provided by Razi Herbal Medicines Research Center, and Lorestan University of Medical Sciences, Iran.

Author information

Authors and Affiliations

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

    Sobhan Rahimi Monfared, Ali Valibeik & Mohammad Nabi Moradi

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

    Sobhan Rahimi Monfared & Ali Valibeik

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

    Sobhan Rahimi Monfared & Ali Valibeik

  4. Department of Medical Biotechnology, School of Allied Medical Sciences, Qazvin University of Medical Sciences, Qazvin, Iran

    Niloufar Tavakoli Dastjerd

  5. Department of Anatomy, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran

    Leila Jafaripour

  6. Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran

    Ashkan Jafarian

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

    Hassan Ahmadvand

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  1. Sobhan Rahimi Monfared
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Contributions

SRM, AV, LJ, NTD and AJ participated in data collection and drafting of the manuscript, data analysis, and performance of the interpretation. HA, MNM, SRM and AV provided conception and design of the study. SRM, AV, LJ and NTD writing an article and revision of the article. All authors reviewed the manuscript.

Corresponding author

Correspondence to Hassan Ahmadvand.

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Conflict of interest

The authors declare no conflict of interest. For the time being, we prove that, we have not submitted the article to any other journals.

Ethics approval

All animal experiments in this research are approved by the ethics committee of Lorestan University of Medical Sciences, Iran (IR.lums.REC.1396.358) based on internationally accepted guidelines for the usage of animals.

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Not applicable, because the study is experimental.

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Rahimi Monfared, S., Valibeik, A., Tavakoli Dastjerd, N. et al. Protective role of citronellol on antioxidant enzymes and oxidative damage induced by gentamicin in experimental nephrotoxic rats. Mol Biol Rep 51, 382 (2024). https://doi.org/10.1007/s11033-024-09212-2

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