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Boron, a Trace Mineral, Alleviates Gentamicin-Induced Nephrotoxicity in Rats

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Abstract

The present study was considered to assess the protective effects of boron (B) on gentamicin-induced oxidative stress, proinflammatory cytokines, and histopathological changes in rat kidneys. Rats were split into eight equal groups which were as follows: control (fed with low-boron diet); gentamicin group (100 mg/kg, i.p.); B5, B10, and B20 (5, 10, and 20 mg/kg B, i.p.) groups; gentamicin (100 mg/kg, i.p.) plus B5, B10, and B20 (5, 10, and 20 mg/kg B, i.p.) groups. B was given to rats 4 days before the gentamicin treatment and B administration was completed on the 14th day. Gentamicin administration was started on the 4th day and finished on the 12th day. Gentamicin increased malondialdehyde levels, while reduced glutathione levels in the blood and kidney. Furthermore, superoxide dismutase and catalase activities of erythrocyte were decreased. Besides, serum and kidney nitric oxide and 8-dihydroxyguanidine levels were increased by gentamicin. Additionally, serum levels and kidney mRNA expressions of TNF-α, NFκB, IL-1β, and IFN-γ were found to be the highest in the gentamicin group. Histopathologically, interstitial hemorrhage and tubular necrosis were detected in the kidneys of the gentamicin group. Nonetheless, B administration reversed gentamicin-induced lipid peroxidation, antioxidant status, and inflammation. In conclusion, B has a preventive effect against gentamicin-induced nephrotoxicity and ameliorates kidney tissues of the rat.

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References

  1. Lode H, Kemmerich B, Koeppe P (2012) Comparative clinical pharmacology of gentamicin, sisomicin, and tobramycin. Antimicrob Agents Chemother 8:396–401

    Google Scholar 

  2. Martin J, Barras M, Ah Yui N, Kirkpatrick C, Kubler P, Norris R (2012) Gentamicin monitoring practices in teaching hospitals–time to undertake the necessary randomised controlled trial. J Clin Toxicol 2(8):1–5

    Google Scholar 

  3. Karahan I, Ateşşahin A, Yilmaz S, Ceribaşi AO, Sakin F (2005) Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats. Toxicology 215:198–204

    CAS  PubMed  Google Scholar 

  4. Khan SA, Priyamvada S, Farooq N, Khan S, Khan MW, Yusufi AN (2009) Protective effect of green tea extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Pharmacol Res 59:254–262

    CAS  PubMed  Google Scholar 

  5. Lee IC, Kim SH, Lee SM, Baek HS, Moon C, Kim SH, Park SC, Kim HC, Kim JC (2012) Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats. Arch Toxicol 86:1527–1536

    CAS  PubMed  Google Scholar 

  6. Randjelovic P, Veljkovic S, Stojiljkovic N, Jankovic-Velickovic L, Sokolovic D, Stoiljkovic M, Ilic I (2012) Salicylic acid attenuates gentamicin-induced nephrotoxicity in rats. Sci World J 2012:1–6

    Google Scholar 

  7. Park JW, Bae EH, Kim IJ, Ma SK, Choi C, Lee J, Kim SW (2010) Renoprotective effects of paricalcitol on gentamicin-induced kidney injury in rats. Am J Physiol Physiol 298:301–313

    Google Scholar 

  8. Bae EH, Kim IJ, Joo SY, Kim EY, Choi JS, Kim CS, Ma SK, Lee J, Kim SW (2014) Renoprotective effects of the direct renin inhibitor aliskiren on gentamicin-induced nephrotoxicity in rats. J Renin-Angiotensin-Aldosterone Syst 15:348–361

    PubMed  Google Scholar 

  9. Nielsen FH (2018) Boron in aging and longevity. In: Trace elements and minerals in health and longevity. Springer, Cham, pp 163–177

    Google Scholar 

  10. Ince S, Erdogan M, Demirel HH, Agca Y, Dal G, Uguz C (2018) Boron enhances early embryonic gene expressions and improves fetal development of rats. J Trace Elem Med Biol 50:34–46

    CAS  PubMed  Google Scholar 

  11. Kucukkurt I, Akbel E, Karabag F, Ince S (2015) The effects of dietary boron compounds in supplemented diet on hormonal activity and some biochemical parameters in rats. Toxicol Ind Health 31:255–260

    CAS  PubMed  Google Scholar 

  12. Türkez H, Geyikoğlu F, Tatar A, Keleş S, Özkan A (2007) Effects of some boron compounds on peripheral human blood. Zeitschrift fur Naturforsch - Sect C J Biosci 62:889–896

    Google Scholar 

  13. Ince S, Kucukkurt I, Cigerci IH, Fidan AF, Eryavuz A (2010) The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats. J Trace Elem Med Biol 24:161–164

    CAS  PubMed  Google Scholar 

  14. Çelikezen FÇ, Toğar B, Özgeriş FB, Izgi MS, Türkez H (2016) Cytogenetic and oxidative alterations after exposure of cultured human whole blood cells to lithium metaborate dehydrate. Cytotechnology 68(4):821–827

    PubMed  Google Scholar 

  15. Coban FK, Ince S, Kucukkurt I, Demirel HH, Hazman O (2015) Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats. Drug Chem Toxicol 38:391–399

    CAS  PubMed  Google Scholar 

  16. Acaroz U, Ince S, Arslan-Acaroz D, Gurler Z, Demirel HH, Kucukkurt I, Eryavuz A, Kara R, Varol N, Zhu K (2019) Bisphenol-A induced oxidative stress, inflammatory gene expression, and metabolic and histopathological changes in male Wistar albino rats: Protective role of boron. Toxicol Res 8:262–269

    CAS  Google Scholar 

  17. Ince S, Kucukkurt I, Acaroz U, Arslan-Acaroz D, Varol N (2019) Boron ameliorates arsenic-induced DNA damage, proinflammatory cytokine gene expressions, oxidant/antioxidant status, and biochemical parameters in rats. J Biochem Mol Toxicol 33:1–7

    Google Scholar 

  18. Yildirim S, Celikezen FC, Oto G, Sengul E, Bulduk M, Tasdemir M, Cinar DA (2018) An investigation of protective effects of litium borate on blood and histopathological parameters in acute cadmium-induced rats. Biol Trace Elem Res 182(2):287–294

    CAS  PubMed  Google Scholar 

  19. Acaroz U, Ince S, Arslan-Acaroz D, Gurler Z, Kucukkurt I, Demirel HH, Arslan HO, Varol N, Zhu K (2018) The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats. Food Chem Toxicol 118:745–752

    CAS  PubMed  Google Scholar 

  20. Hunt CD (1996) In: Watson RR (ed) Dietary boron deficiency and supplementation. CRC Press, Inc, New York, pp 229–254

    Google Scholar 

  21. Ince S, Kucukkurt I, Demirel HH, Acaroz DA, Akbel E, Cigerci IH (2014) Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats. Chemosphere 108:197–204

    CAS  PubMed  Google Scholar 

  22. Ateşşahin A, Karahan I, Yilmaz S, Çeribaşi AO, Princci I (2003) The effect of manganese chloride on gentamicin-induced nephrotoxicity in rats. Pharmacol Res 48:637–642

    PubMed  Google Scholar 

  23. Winterbourn CC, Hawkins RE, Brain M, Carrell RW (1975) The estimation of red cell superoxide activity. J Lab Clin Med 55:337–341

    Google Scholar 

  24. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    CAS  PubMed  Google Scholar 

  25. Draper HH, Hardley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431

    CAS  PubMed  Google Scholar 

  26. Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  PubMed  Google Scholar 

  27. Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxidase dismutase. Clin Chem 34:497–500

    CAS  PubMed  Google Scholar 

  28. Luck H (1955) Methods in analysis. In: Methods in analysis. Academy Press, London

    Google Scholar 

  29. Aebi H (1974) Catalase. In: Methods of enzymatic analysis, pp 673–677

    Google Scholar 

  30. Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide Biol Chem 5:62–71

    CAS  Google Scholar 

  31. Lowry O, Rosebrough N, Farr A, Randall R (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  32. Drabkin DL, Austin JH (1935) Spectrophotometric studies. II. Preparations from washed 112, blood cells; nitric oxide hemoglobin and sulfhemoglobin. J Biol Chem:51–65

  33. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Salem EA, Salem NA, Kamel M, Maarouf AM, Bissada NK, Hellstrom WJ, El-Adl M (2010) Amelioration of gentamicin nephrotoxicity by green tea extract in uninephrectomized rats as a model of progressive renal failure. Ren Fail 32:1210–1215

    CAS  PubMed  Google Scholar 

  35. Abdelsameea AA, Mohamed AM, Amer MG, Attia SM (2016) Cilostazol attenuates gentamicin-induced nephrotoxicity in rats. Exp Toxicol Pathol 68:247–253

    CAS  PubMed  Google Scholar 

  36. Kuhad A, Tirkey N, Pilkhwal S, Chopra K (2006) Effect of Spirulina, a blue green algae, on gentamicin-induced oxidative stres and renal dysfunction in rats. Fundam Clin Pharmacol 20:121–128

    CAS  PubMed  Google Scholar 

  37. Dungca NT (2016) Protective effect of the methanolic leaf extract of Eclipta alba (L.) Hassk. (Asteraceae) against gentamicin-induced nephrotoxicity in Sprague Dawley rats. J Ethnopharmacol 184:18–21

    CAS  PubMed  Google Scholar 

  38. Kasztan M, Jankowski M (2016) Involvement of P2 receptors in regulation of glomerular permeability to albumin by extracellular nucleotides of intra-/extra-glomerular origins. J Physiol Pharmacol 67:177–183

    CAS  PubMed  Google Scholar 

  39. Moreira MA, Nascimento MA, Bozzo TA, Cintra A, da Silva SM, Dalboni MA, Mouro MG, Higa EM (2014) Ascorbic acid reduces gentamicin-induced nephrotoxicity in rats through the control of reactive oxygen species. Clin Nutr 33:296–301

    CAS  PubMed  Google Scholar 

  40. Parlakpinar H, Tasdemir S, Polat A, Bay-Karabulut A, Vardi N, Ucar M, Acet A (2005) Protective role of caffeic acid phenethyl ester (cape) on gentamicin-induced acute renal toxicity in rats. Toxicology 207:169–177

    CAS  PubMed  Google Scholar 

  41. Yaman I, Balikci E (2010) Protective effects of nigella sativa against gentamicin-induced nephrotoxicity in rats. Exp Toxicol Pathol 62:183–190

    PubMed  Google Scholar 

  42. Samarghandian S, Azimi-Nezhad M, Mehrad-Majd H, Mirhafez SR (2015) Thymoquinone ameliorates acute renal failure in gentamicin-treated adult male rats. Pharmacology 96:112–117

    CAS  PubMed  Google Scholar 

  43. Mahmoud AM, Ahmed OM, Galaly SR (2014) Thymoquinone and curcumin attenuate gentamicininduced renal oxidative stress, inflammation and apoptosis in rats. EXCLI J 13:98–110

    PubMed  PubMed Central  Google Scholar 

  44. Fouad AA, Albualib WH, Zahranc A, Gomaa W (2014) Protective effect of naringenin against gentamicin-induced nephrotoxicity in rats. Environ Toxicol Pharmacol 38:420–429

    CAS  PubMed  Google Scholar 

  45. Yoshioka N, Nakashima H, Hosoda K, Eitaki Y, Shimada N, Omae K (2008) Urinary excretion of an oxidative stress marker, 8-hydroxyguanine (8-OH-GUA), among nickel-cadmium battery workers. J Occup Health 50:229–235

    CAS  PubMed  Google Scholar 

  46. Gałazyn-Sidorczuk M, Brzóska MM, Jurczuk M, Moniuszko-Jakoniuk J (2009) Oxidative damage to proteins and DNA in rats exposed to cadmium and/or ethanol. Chem Biol Interact 180:31–38

    PubMed  Google Scholar 

  47. Iqbal M, Okazaki Y, Okada S (2009) Curcumin attenuates oxidative damage in animals treated with a renal carcinogen, ferric nitrilotriacetate (Fe-NTA): Implications for cancer prevention. Mol Cell Biochem 324:157–164

    CAS  PubMed  Google Scholar 

  48. Li Z, Piao F, Liu S, Wang Y, Qu S (2010) Subchronic exposure to arsenic trioxide-induced oxidative DNA damage in kidney tissue of mice. Exp Toxicol Pathol 62:543–547

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  50. Sahu BD, Tatireddy S, Koneru M, Borkar RM, Kumar JM, Kuncha M, Srinivas R, Shyam-Sunder R, Sistla R (2014) Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection. Toxicol Appl Pharmacol 277:8–20

    CAS  PubMed  Google Scholar 

  51. Subramanian P, Anandan R, Jayapalan JJ, Hashim OH (2015) Hesperidin protects gentamicin-induced nephrotoxicity via Nrf2/HO-1 signaling and inhibits inflammation mediated by NF-κB in rats. J Funct Foods 13:89–99

    CAS  Google Scholar 

  52. Veljković M, Pavlović DR, Stojiljković N, Ilić S, Petrović A, Jovanović I, Radenković M (2016) Morphological and morphometric study of protective effect of green tea in gentamicin-induced nephrotoxicity in rats. Life Sci 147:85–91

    PubMed  Google Scholar 

  53. Quirós Y, Blanco-Gozaloa V, Sanchez-Gallegoa JI, López-Hernandez FJ, Ruize J, Perez de Obanose MP, López-Novoab JM (2016) Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicityin rats. Pharmacol Res 107:137–146

    PubMed  Google Scholar 

  54. Armstrong TA, Spears JW (2003) Effect of boron supplementation of pig diets on the production of tumor necrosis factor-α and interferon-γ. J Anim Sci 81:2552–2561

    CAS  PubMed  Google Scholar 

  55. Hegazy AMS, Mosaed MM, Elshafey SH, Bayomy NA (2016) 6-Gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats. Tissue Cell 48:208–216

    CAS  PubMed  Google Scholar 

  56. Stojiljkovic N, Stoiljkovic M, Randjelovic P, Veljkovic S, Mihailovic D (2012) Cytoprotective effect of vitamin C against gentamicin-induced acute kidney injury in rats. Exp Toxicol Pathol 64:69–74

    CAS  PubMed  Google Scholar 

  57. Sun X, Zhang B, Hong X, Zhang X, Kong X (2013) Histone deacetylase inhibitor, sodium butyrate, attenuates gentamicin-induced nephrotoxicity by increasing prohibitin protein expression in rats. Eur J Pharmacol 707:147–154

    CAS  PubMed  Google Scholar 

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Acknowledgment

Also, this study orally presented at 3rd International Turkic World Conference on Chemical Sciences and Technologies (ITWCCST 2017).

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This study was financially supported by a grant (Project Number: 214O661) from the Scientific and Technological Research Council of Turkey.

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Correspondence to Sinan Ince.

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Ince, S., Kucukkurt, I., Demirel, H.H. et al. Boron, a Trace Mineral, Alleviates Gentamicin-Induced Nephrotoxicity in Rats. Biol Trace Elem Res 195, 515–524 (2020). https://doi.org/10.1007/s12011-019-01875-4

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