Carvacrol attenuates amikacin-induced nephrotoxicity in the rats

Abstract

Objective: Amikacin (AK) is a wide-spectrum antibiotic routinely used to treat gram-negative and some gram-positive bacterial infections. However, its use is limited due to its potential to cause nephrotoxicity due to an increase in reactive oxygen radicals. The main goal of this study was to investigate the effect of carvacrol (CAR) on AK-induced nephrotoxicity in rats. Methods: Thirty-two Sprague Dawley rats were randomly separated into four groups: the control (0.9% NaCl solution and sunflower oil), AK (400 mg/kg), CAR+AK (80 mg/kg CAR+400 mg/kg AK), and AK+CAR (400 mg/kg AK+80 mg/kg CAR) groups. AK and CAR were administered intramuscularly and orally, respectively for 7 days. Blood and kidney tissue samples were collected at the end of the experiment. The level of catalase, superoxide dismutase, malondialdehyde, and reduced glutathione, which are parameters of oxidative stress, were detected while comparing renal function and histopathological changes. Results: Histopathological findings (necrotic changes, dilatation and inflammatory cell infiltration) were significantly greater in the AK group than in the control group. Additionally, significant weight loss was detected in the rats in the AK group. CAR treatment, both before and after AK administration, significantly improved nephrotoxicity histopathologically (p<.05). However, the same improvement was not identified biochemically. Conclusion: CAR treatment significantly improved nephrotoxicity both before and after AK administration, suggesting that carvacrol has a protective effect against AK-induced kidney damage at the histopathological level. Keywords: Antioxidant, amikacin, carvacrol, nephrotoxicity, oxidative stress, rat

Keywords

• Antioxidant
• amikacin
• carvacrol
• nephrotoxicity
• oxidative stress
• rat

References

1. Abd El-Kader, M., & Taha, R. I. (2020). Comparative nephroprotective effects of curcumin and etoricoxib against cisplatin-induced acute kidney injury in rats. Acta Histochem, 122(4), 151534.
2. Abdel-Daim, M. M., Batiha, G. E.-S., Othman, E. M., & Abdel-Wahhab, M. A. (2019). Influence of Spirulina platensis and ascorbic acid on amikacin-induced nephrotoxicity in rabbits. Environmental Science and Pollution Research International, 26(8), 8080–8086.
3. Abdel-Gayoum, A. A., El-Kahtany, M. A., & Abdelhamid, S. A. (2015). The ameliorative effects of virgin olive oil and olive leaf extract on amikacin-induced nephrotoxicity in the rat. Toxicology Reports, 2, 1327–1333.
4. Abdelhamid, A. M., El-Kasaby, M. M., & Shaheen, H. M. (2020). Protective effect of cerium oxide nanoparticles on cisplatin and oxaliplatin primary toxicities in male albino rats. Naunyn-Schmiedeberg’s Archives of Pharmacology, 393(12), 2411–2425.
5. Ahmed, S., Mehmood, R., & Khan, M. N. (2020). Retention of antibiotic activity against resistant bacteria harbouring aminoglycoside-N-acetyltransferase enzyme by adjuvants: A combination of in-silico and in-vitro study. Scientific Reports, 10(1), 19381.
6. Ahmed, Z. S. O., Khedher, N. B., & Ali, M. M. (2021). Evaluation of the effect of methotrexate on the hippocampus, cerebellum, liver, and kidneys of adult male albino rat: Histopathological, immunohistochemical and biochemical studies. Acta Histochem, 123(2), 151682.
7. Al-Kuraishy, H. M., Al-Gareeb, A., & Hussien, N. R. (2019). Betterment of diclofenac-induced nephrotoxicity by pentoxifylline through modulation of inflammatory biomarkers. Asian Journal of Pharmaceutical and Clinical Research, 12(3), 433–437.
8. Arigesavan, K., & Sudhandiran, G. (2015). Carvacrol exhibits antioxidant and anti-inflammatory effects against 1,2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats. Biochemical and Biophysical Research Communications, 461(2), 314–320.

9. Arslan, A., Kucuk, A., & Genc, H. (2018). WSSPAS: Web-based sample size & power analysis software. Turkiye Klinikleri Journal of Biostatistics, 3, 1–34.
10. Asci, H., Yilmaz, A., & Bozkurt, M. (2015). The impact of alpha-lipoic acid on amikacin-induced nephrotoxicity. Renal Failure, 37(1), 117–121.
11. Baltaci, A. K., Mogulkoc, R., & Kizir, M. A. (2019). The effects of resveratrol administration on lipid oxidation in experimental renal ischemia-reperfusion injury in rats. Biotechnology & Histochemistry, 94(8), 592–599.
12. Banji, O. J., Banji, D., & Rai, V. (2014). Combination of carvacrol with methotrexate suppresses Complete Freund's Adjuvant induced synovial inflammation with reduced hepatotoxicity in rats. European Journal of Pharmacology, 723, 91–98.
13. Bulut, G., Yalçın, M., & Arslan, M. (2016). Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model. Renal Failure, 38(5), 751–758.
14. Çolak, C., & Parlakpınar, H. (2012). Hayvan deneyleri: In vivo denemelerin bildirimi: ARRIVE Kılavuzu-Derleme. da Silva Lima, M., da Silva, L. C., & da Silva, J. M. (2013). Anti-inflammatory effects of carvacrol: Evidence for a key role of interleukin-10. European Journal of Pharmacology, 699(1–3), 112–117.
15. El-Kashef, D. H., Sayed, R. M., & El-Sayed, H. S. (2015). Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats. Naunyn-Schmiedeberg’s Archives of Pharmacology, 388(12), 1305–1315.
16. Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82(1), 70–77.
17. Garcia, D., da Silva, R. S., & Vieira, J. A. (2020). Decreased malondialdehyde levels in fish (Astyanax altiparanae) exposed to diesel: Evidence of metabolism by aldehyde dehydrogenase in the liver and excretion in water. Ecotoxicology and Environmental Safety, 190, 110107.
18. Ghorani, V., Hedayati, M., & Davoodvandi, A. (2021). Safety and tolerability of carvacrol in healthy subjects: A phase I clinical study. Drug and Chemical Toxicology, 44(2), 177–189.
19. Gunata, M., & Parlakpinar, H. (2020). A review of myocardial ischemia/reperfusion injury: Pathophysiology, experimental models, biomarkers, genetics and pharmacological treatment. Cell Biochemistry and Function.
20. Hiller, A., Greif, R. L., & Beckman, W. W. (1948). Determination of protein in urine by the biuret method. Journal of Biological Chemistry, 176(3), 1421–1429.
21. Hoste, E. A., Kellum, J. A., & Ronco, C. (2015). Epidemiology of acute kidney injury in critically ill patients: The multinational AKI-EPI study. Intensive Care Medicine, 41(8), 1411–1423.
22. Ili, P., & Keskin, N. (2013). A histochemical study of ultraviolet B irradiation and Origanum hypericifolium oil applied to the skin of mice. Biotechnology & Histochemistry, 88(5), 272–279.
23. Jenkins, R. R. (2000). Exercise and oxidative stress methodology: A critique. The American Journal of Clinical Nutrition, 72(2), 670S–674S.
24. Kamendulis, L. M., Kline, K., & Monks, T. J. (1999). Induction of oxidative stress and oxidative damage in rat glial cells by acrylonitrile. Carcinogenesis, 20(8), 1555–1560.
25. Kang, K. Y., Ryu, J. C., & Lee, K. H. (2011). Calretinin immunoreactivity in normal and carbon tetrachloride-induced nephrotoxic rats. Acta Histochem, 113(7), 712–716.
26. Kapucu, A. (2021). Crocin ameliorates oxidative stress and suppresses renal damage in streptozotocin induced diabetic male rats. Biotechnology & Histochemistry, 96(2), 153–160.
27. Kara, A., Yalçın, A., & Altuntas, I. (2016). Amikacin induced renal damage and the role of the antioxidants on neonatal rats. Renal Failure, 38(5), 671–677.
28. Khosravi, A. R., & Erle, D. J. (2016). Chitin-induced airway epithelial cell innate immune responses are inhibited by carvacrol/thymol. PLoS One, 11(7), e0159459.
29. Kose, E., Yilmaz, A., & Kose, A. (2012). The effects of montelukast against amikacin-induced acute renal damage. European Review for Medical and Pharmacological Sciences, 16(4), 503–511.
30. Krause, K. M., Zong, J., & Kellerman, M. (2016). Aminoglycosides: An overview. Cold Spring Harbor Perspectives in Medicine, 6(6), a027029.
31. Lima, D., Silva, F. A., & Oliveira, S. (2019). Stress responses in Crassostrea gasar exposed to combined effects of acute pH changes and phenanthrene. Science of The Total Environment, 678, 585–593.
32. Liu, X., Zhang, S., & Wang, J. (2020). MicroRNA as an early diagnostic biomarker for contrast-induced acute kidney injury. Drug and Chemical Toxicology, 1–6.
33. Lopez-Novoa, J. M., Morales, A. I., & Martínez, R. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity: An integrative point of view. Kidney International, 79(1), 33–45.
34. Luck, H. (1974). Estimation of catalase activity. In Methods of Enzymology (Vol. 885). Academic Press.
35. Ma’rifah, F., Anwar, A., & Hasan, M. (2019). The change of metallothionein and oxidative response in gills of the Oreochromis niloticus after exposure to copper. Animals, 9(6), 353.
36. McGrath, L., Wang, Q., & Zhang, Q. (2001). Increased oxidative stress in Alzheimer's disease as assessed with 4‐hydroxynonenal but not malondialdehyde. QJM: An International Journal of Medicine, 94(9), 485–490.
37. McWilliam, S. J., & Coombes, J. D. (2017). Aminoglycoside-induced nephrotoxicity in children. Pediatric Nephrology, 32(11), 2015–2025.
38. Melo, F. H., de Almeida, M., & Silva, A. (2011). Antidepressant-like effect of carvacrol (5-isopropyl-2-methylphenol) in mice: Involvement of dopaminergic system. Fundamental & Clinical Pharmacology, 25(3), 362–367.
39. Mirazi, N., Gharaghani, M., & Jahangir, M. (2021). Treatment with human umbilical cord blood serum in a gentamicin-induced nephrotoxicity model in rats. Drug and Chemical Toxicology, 1–7.
40. Mishra, A. P., & Suman, J. (2018). Programmed cell death, from a cancer perspective: An overview. Molecular Diagnosis & Therapy, 22(3), 281–295.
41. Ohta, Y., & Nishida, K. (2003). Protective effect of coadministered superoxide dismutase and catalase against stress-induced gastric mucosal lesions. Clinical and Experimental Pharmacology and Physiology, 30(8), 545–550.
42. Oliveira, I. S., Lima, C. M., & Barbosa, R. M. (2012). Gastroprotective activity of carvacrol on experimentally induced gastric lesions in rodents. Naunyn-Schmiedeberg’s Archives of Pharmacology, 385(9), 899–908.
43. Ozer, M. K., Ozer, F., & Erdal, M. (2020). Thymoquinone protection from amikacin induced renal injury in rats. Biotechnology & Histochemistry, 95(2), 129–136.
44. Ozturk, H., Avci, A., & Aydin, M. (2018). Carvacrol attenuates histopathologic and functional impairments induced by bilateral renal ischemia/reperfusion in rats. Biomedicine & Pharmacotherapy, 98, 656–661.
45. Parlakpinar, H., Sener, G., & Cakir, S. (2004). Protective effect of aminoguanidine against nephrotoxicity induced by amikacin in rats. Urological Research, 32(4), 278–282.
46. Parlakpinar, H., Polat, A., & Aslan, M. (2003). Amikacin-induced acute renal injury in rats: Protective role of melatonin. Journal of Pineal Research, 35(2), 85–90.
47. Parlakpinar, H., Yildirim, A., & Turkmen, N. (2006). Protective effects of caffeic acid phenethyl ester (CAPE) on amikacin-induced nephrotoxicity in rats. Cell Biochemistry and Function, 24(4), 363–367.
48. Peasley, K., & VandeBerg, J. L. (2021). Sirtuins play critical and diverse roles in acute kidney injury. Pediatric Nephrology, 1–8.
49. Perazella, M. A. (2018). Pharmacology behind common drug nephrotoxicities. Clinical Journal of the American Society of Nephrology, 13(12), 1897–1908.
50. Polat, A., Yilmaz, N., & Yilmaz, O. (2006). Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats. Acta Histochemica, 108(5), 365–371.
51. Potočnjak, I., & Domitrović, R. (2016). Carvacrol attenuates acute kidney injury induced by cisplatin through suppression of ERK and PI3K/Akt activation. Food and Chemical Toxicology, 98, 251–261.
52. Raeeszadeh, M., & Sadeghi, M. (2021). The comparison of the effect of Origanum vulgare L. extract and vitamin C on the gentamycin-induced nephrotoxicity in rats. Drug and Chemical Toxicology, 1–8.
53. Rehman, M. U., & Pasha, I. (2014). Alleviation of hepatic injury by chrysin in cisplatin administered rats: Probable role of oxidative and inflammatory markers. Pharmacological Reports, 66(6), 1050–1059.
54. Ronco, C., Bellomo, R., & Kellum, J. A. (2019). Acute kidney injury. The Lancet, 394(10212), 1949–1964.
55. Sahay, M., Kalra, S., & Bandgar, T. (2012). Renal endocrinology: The new frontier. Indian Journal of Endocrinology and Metabolism, 16(2), 154–155.
56. Samarghandian, S., Moghaddam, H. R., & Azimi-Nezhad, M. (2016). Protective effects of carvacrol against oxidative stress induced by chronic stress in rat's brain, liver, and kidney. Biochemical Research International, 2016, 2645237.
57. Selim, A., & Khan, M. (2017). Evaluation of the possible nephroprotective effects of vitamin E and rosuvastatin in amikacin-induced renal injury in rats. Journal of Biochemical and Molecular Toxicology, 31(11), e21957.
58. Shahrokhi Raeini, A., & Naseri, R. (2020). Carvacrol suppresses learning and memory dysfunction and hippocampal damages caused by chronic cerebral hypoperfusion. Naunyn-Schmiedeberg’s Archives of Pharmacology, 393(4), 581–589.
59. Sharma, S., & Sood, S. (2021). Betaine attenuates sodium arsenite-induced renal dysfunction in rats. Drug and Chemical Toxicology, 1–8.
60. Sun, Y., Oberley, L. W., & Li, Y. (1988). A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 34(3), 497–500.
61. Suntres, Z. E., Coccimiglio, J., & Alipour, M. (2015). The bioactivity and toxicological actions of carvacrol. Critical Reviews in Food Science and Nutrition, 55(3), 304–318.
62. Suo, L., Yang, F., & Xu, G. (2014). Carvacrol alleviates ischemia reperfusion injury by regulating the PI3K-Akt pathway in rats. PLoS One, 9(8), e104043.
63. Sweileh, W. M. (2009). A prospective comparative study of gentamicin- and amikacin-induced nephrotoxicity in patients with normal baseline renal function. Fundamental & Clinical Pharmacology, 23(4), 515–520.
64. Szczepanik, W., Kaczmarek, P., & Jezowska-Bojczuk, M. (2004). Oxidative activity of copper(II) complexes with aminoglycoside antibiotics as implication to the toxicity of these drugs. Bioinorganic Chemistry and Applications, 2(1–2), 55–68.
65. Ubani-Rex, O. A., Saliu, J. K., & Bello, T. H. (2017). Biochemical effects of the toxic interaction of copper, lead, and cadmium on Clarias gariepinus. Journal of Health and Pollution, 7(16), 38–48.
66. Uchiyama, M., & Mihara, M. (1978). Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Analytical Biochemistry, 86(1), 271–278.
67. Ultee, A., Kets, E. P. W., & Smid, E. J. (1999). Mechanisms of action of carvacrol on the food-borne pathogen Bacillus cereus. Applied and Environmental Microbiology, 65(10), 4606–4610.
68. Ulusoy, S., & Karaoglu, H. (2012). The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy. Renal Failure, 34(2), 227–234.
69. Wargo, K. A., & Edwards, J. D. (2014). Aminoglycoside-induced nephrotoxicity. Journal of Pharmacy Practice, 27(6), 573–577.
70. Xiong, S., Wang, S., & Zhang, X. (2015). PGC-1alpha modulates telomere function and DNA damage in protecting against aging-related chronic diseases. Cell Reports, 12(8), 1391–1399.
71. Yang, L. H., Zhang, X., & Wei, X. (2017). Protective role of piceatannol in amikacin-induced renal damage in neonatal rats. Biomedical Research (India), 28(3), 1142–1147.
72. Yılmaz, F. Ö., Altıok, A., & Sönmez, A. (2018). Protective effect of humic substances against oxidative stress caused by lead in liver of Nile tilapia, Oreochromis niloticus (Linnaeus, 1758). Turkish Journal of Agriculture and Food Science and Technology, 6(8), 1015–1021.
73. Zare Mehrjerdi, F., & Parsa, M. (2020). Carvacrol reduces hippocampal cell death and improves learning and memory deficits following lead-induced neurotoxicity via antioxidant activity. Naunyn-Schmiedeberg’s Archives of Pharmacology, 393(7), 1229–1237.