Advertisement

Propolis and Its Combination with Boric Acid Protect Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Oxidative Stress, Inflammation, DNA Damage, and Apoptosis in Rats

  • Fatime Geyikoglu
  • Kubra KocEmail author
  • Suat Colak
  • Huseyin Serkan Erol
  • Salim Cerig
  • Berna Kavakcioglu Yardimci
  • Ozge Cakmak
  • Muhammed Bahaeddin Dortbudak
  • Gizem Eser
  • Ferhunde Aysin
  • Nihal Simsek Ozek
  • Serkan Yildirim
Article

Abstract

Ischemia reperfusion (I/R) injury which causes kidney dysfunction is one of the most studied diseases directly linked to oxidative stress. In this regard, it is important to protect cells against damage by inducing antioxidant response. Herein, we aimed to evaluate the therapeutic roles and possible mechanisms of propolis and boric acid in kidney I/R injury based on relevant basic research and clinical studies. Sprague-Dawley rats were subjected to 50 min of ischemia followed by 3 h of reperfusion. Animals were randomly divided into a control group (the abdominal wall was just opened and closed), an I/R injury group, the propolis intervention group (200 mg/kg, intragastric administration, 1 h before ischemia), boric acid intervention group (14 mg/kg, intragastric administration 1 h before ischemia), and the propolis + boric acid intervention group (intragastric administration 1 h before ischemia). Kidney function, the antioxidant defensive system, and renal damage were assessed. In addition, the oxidative stress and inflammatory status were estimated in renal tissue. Furthermore, DNA damageand apoptosis were detected by immunohistochemistry. When compared with I/R group, propolis alone and especially propolis + boric acid groups significantly improved functional parameters. While the antioxidant response was increased, renal injury size and apoptosis were significantly decreased in both groups. Also, the MDA and TNF-α levels besides the 8-OHdG formation were downregulated. According to these outcomes, it can be said that especially propolis together with boric acid ameliorates kidney injury caused by I/R through acting as an antioxidant, anti-inflammatory, and antiapoptotic agent. In conclusion, propolis alone and its combination with boric acid could be developed as therapeutic agents against serious renal I/R injuries.

Keywords

Ischemia/reperfusion Propolis Boric acid Kidney Oxidative stress Inflammation 

Notes

Compliance with Ethical Standards

Experiments were performed according to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication No. 85-23, revised 1996). All experimental procedures in this study were approved by the Atatürk University Local Ethics Committee for Animal Experiments (No. 66, 22.03.2018).

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Ito R, Kumada Y, Ishii H, Kamoi D, Sakakibara T, Umemoto N, Takahashi H, Murohara T (2018) Clinical outcomes after isolated infrapopliteal revascularization in hemodialysis patients with critical limb ischemia: endovascular therapy versus bypass surgery. J Atheroscler Thromb 25:799–807Google Scholar
  2. 2.
    Xu Z, Dai C (2017) Ablation of FGFR2 in fibroblasts ameliorates kidney fibrosis after ischemia/reperfusion injury in mice. Kidney Dis 3:160–170CrossRefGoogle Scholar
  3. 3.
    Goetz L, Laskowski J, Renner B, Pickering MC, Kulik L, Klawitter J, Stites E, Christians U, van derVlag J, Ravichandran K, Holers VM, Thurman JM (2018) Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM. Eur J Immunol 1Google Scholar
  4. 4.
    Cheungpasitporn W, Khoury NJ, Thongprayoon C, Craici IM (2017) Is remote ischemic conditioning of benefit to patients undergoing kidney transplantation? J Investig Surg 12:1–3CrossRefGoogle Scholar
  5. 5.
    Song Y, Liu W, Ding Y, Jia YY, Zhao J, Wang F, Bai J, Cheng L, Gao K, Liu M, Yao M, Li L, Zhang Y, Wen A, He L (2018) Salvianolic acid A ameliorates renal ischemia/reperfusion injury by activating Akt/mTOR/4EBP1 signaling pathway. Am J Physiol Renal Physiol 315:F254–F262Google Scholar
  6. 6.
    Martinotti S, Bucekova M, Majtan J, Ranzato E (2018) Honey: an effective regenerative medicine product in wound management. Curr Med Chem.  https://doi.org/10.2174/0929867325666180510141824
  7. 7.
    Farooqui T, Farooqui AA (2012) Beneficial effects of propolis on human health and neurological diseases. Front Biosci (Elite Ed) 4:779–793CrossRefGoogle Scholar
  8. 8.
    Bankova V, Popova M, Trusheva B (2018) The phytochemistry of the honeybee. Phytochemistry 24(155):1–11CrossRefGoogle Scholar
  9. 9.
    Patel S (2016) Emerging adjuvant therapy for cancer: propolis and its constituents. J Diet Suppl 13(3):245–268CrossRefGoogle Scholar
  10. 10.
    Nzietchueng RM, Dousset B, Franck P, Benderdour M, Nabet P, Hess K (2002) Mechanisms implicated in the effects of boron on wound healing. J Trace Elem Med Biol 16(4):239–244CrossRefGoogle Scholar
  11. 11.
    Barranco WT, Eckhert CD (2006) Cellular changes in boric acid-treated DU-145 prostate cancer cells. Br J Cancer 94:884–890CrossRefGoogle Scholar
  12. 12.
    Hakki SS, Bozkurt BS, Hakki EE (2010) Boron regulates mineralized tissue-associated proteins in osteoblasts (MC3T3-E1). J Trace Elem Med Biol 24:243–250CrossRefGoogle Scholar
  13. 13.
    Vijay Bhasker T, Gowda NKS, Krishnamoorthy P, Pal DT, Sejian V, Awachat VB, Verma AK (2017) Boron supplementation provides hepato-protective effect and improves performance in Wistar rats fed calcium deficit diet. Indian J Anim Sci 87(10):1213–1218Google Scholar
  14. 14.
    Moseman RF (1994) Chemical disposition of boron in animals and humans. Environ Health Perspect 102:113–117PubMedPubMedCentralGoogle Scholar
  15. 15.
    WHO; Environ HealthCriteria Document No. 204 (1998): Boron (7740-42-8) p.53Google Scholar
  16. 16.
    Acar Ü, İnanan BE, Zemheri F, Kesbiç OS, Yılmaz S (2018) Acute exposure to boron in Nile tilapia (Oreochromis niloticus): median-lethal concentration (LC50), blood parameters, DNA fragmentation of blood and sperm cells. Chemosphere 213:345–350CrossRefGoogle Scholar
  17. 17.
    Gheisari A, Shahrvand S, Landy N (2017) Effect of ethanolic extract of propolis as an alternative to antibiotics as a growth promoter on broiler performance, serum biochemistry, and immune responses. Vet World 10:249–254CrossRefGoogle Scholar
  18. 18.
    Bahadoran H, Naghii MR, Mofid M, Asadi MH, Ahmadi K, Sarveazad A (2016) Protective effects of boron and vitamin E on ethylene glycol-induced renal crystal calcium deposition in rat. Endocr Regul 50(4):194–206CrossRefGoogle Scholar
  19. 19.
    Choi DE, Jeong JY, Lim BJ, Chung S, Chang YK, Lee SJ, Na KR, Kim SY, Shin YT, Lee KW (2009) Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats. Am J Physiol Renal Physiol 297(2):F362–F370CrossRefGoogle Scholar
  20. 20.
    Yıldırım S (2017) Investigation by histopathological and TUNEL method of the protective effect of resveratrol on carbon tetrachloride induced liver toxicity in rats. Ataturk Univ J Vet Sci 12:178–186Google Scholar
  21. 21.
    Bovo E, Mazurek SR, Zima AV (2018) Oxidation of ryanodine receptor following ischemia/reperfusion increases propensity of Ca2+ waves during β-adrenergic receptor stimulation. Am J Physiol Heart Circ Physiol 315(4):H1032–H1040Google Scholar
  22. 22.
    Cao H, Ou J, Chen L, Zhang Y, Szkudelski T, Delmas D, Daglia M, Xiao J (2018) Dietary polyphenols and type 2 diabetes: human study and clinical trials. Crit Rev Food Sci Nutr 11:1–19CrossRefGoogle Scholar
  23. 23.
    Puspasari A, Harijanti K, Soebadi B, Hendarti HT, Radithia D, Ernawati DS (2018) Effects of topical application of propolis extract on fibroblast growth factor-2 and fibroblast expression in the traumatic ulcers of diabetic Rattus norvegicus. J Oral Maxillofac Pathol 22(1):54–58PubMedPubMedCentralGoogle Scholar
  24. 24.
    da Costa MF, Libório AB, Teles F, Martins Cda S, Soares PM, Meneses GC, Rodrigues FA, Leal LK, Miron D, Silva AH, Martins AM (2015) Red propolis ameliorates ischemic-reperfusion acute kidney injury. Phytomedicine 22(9):787–795CrossRefGoogle Scholar
  25. 25.
    El-Marasy SA, Abdel-Rahman RF, Abd-Elsalam RM (2018) Neuroprotective effect of vildagliptin against cerebral ischemia in rats. Naunyn Schmiedeberg’s Arch Pharmacol 391(10):1133–1145Google Scholar
  26. 26.
    Tanaka A, Ito Y, Kawasaki H, Kitabayashi C, Nishioka R, Yamazato M, Ishizawa K, Nagai T, Hirayama M, Takahashi K, Yamamoto T, Araki N (2018) Effects of memantine on nitric oxide production and hydroxyl radical metabolism during cerebral ischemia and reperfusion in mice. J Stroke Cerebrovasc Dis 27(6):1609–1615CrossRefGoogle Scholar
  27. 27.
    Lungkaphin A, Pongchaidecha A, Palee S, Arjinajarn P, Pompimon W, Chattipakorn N (2015) Pinocembrin reduces cardiac arrhythmia and infarct size in rats subjected to acute myocardial ischemia/reperfusion. Appl Physiol Nutr Metab 40(10):1031–1037CrossRefGoogle Scholar
  28. 28.
    Aldahmash BA, El-Nagar DM, Ibrahim KE (2016) Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice. Nefrologia 36(6):643–652CrossRefGoogle Scholar
  29. 29.
    Mounieb F, Ramadan L, Akool ES, Balah A (2017) Propolis alleviates concanavalin A-induced hepatitis by modulating cytokine secretion and inhibition of reactive oxygen species. Naunyn Schmiedeberg's Arch Pharmacol 390(11):1105–1115CrossRefGoogle Scholar
  30. 30.
    Ince S, Keles H, Erdogan M, Hazman O, Kucukkurt I (2011) Protective effect of boric acid against carbon tetrachloride-induced hepatotoxicity in mice. Drug Chem Toxicol 15:1–8Google Scholar
  31. 31.
    Yazıcı S, Akşit H, Korkut O, Sunay B, Çelik T (2014) Effects of boric acid and 2-aminoethoxydiphenyl borate on necrotizing enterocolitis. J Pediatr Gastroenterol Nutr 58(1):61–67CrossRefGoogle Scholar
  32. 32.
    Hu X, Ma R, Lu J, Zhang K, Xu W, Jiang H, Da Y (2016) IL-23 promotes myocardial I/R injury by increasing the inflammatory responses and oxidative stress reactions. Cell Physiol Biochem 38(6):2163–2172CrossRefGoogle Scholar
  33. 33.
    Tanko Y, Kabiru A, Abdulrasak A, Mohammed KA, Salisu AI, Jimoh A, Gidado NM, Sada NM (2017) Effects of fermented ginger rhizome (Zingiber officinale) and Fenu Greek (Trigonella foenum-graceum) supplements on oxidative stress and lipid peroxidation biomarkers in Poloxamer-407 induced -hyperlipidemic Wistar rats. Niger J Physiol Sci 32(2):137–143PubMedGoogle Scholar
  34. 34.
    Mahalakshmi A, Kurian GA (2018) Evaluating the impact of diabetes and diabetic cardiomyopathy rat heart on the outcome of ischemia-reperfusion associated oxidative stress. Free Radic Biol Med 118:35–43CrossRefGoogle Scholar
  35. 35.
    Cakir S, Eren M, Senturk M, Sarica ZS (2017) The effect of boron on some biochemical parameters in experimental diabetic rats. Biol Trace Elem Res 184(1):165–172CrossRefGoogle Scholar
  36. 36.
    Luo YP, Zhang H, Hu HF, Cao ZY, Zhang XZ, Cao L, Wang ZZ, Xiao W (2017) Protective effects of Ginkgo terpene lactones meglumine injection on focal cerebral ischemia in rats. Zhongguo Zhong Yao Za Zhi 42(24):4733–4737PubMedGoogle Scholar
  37. 37.
    Cao J, Jiang L, Zhang X, Yao X, Geng C, Xue X, Zhong L (2008) Boric acid inhibits LPS-induced TNF-alpha formation through a thiol-dependent mechanism in THP-1 cells. J Trace Elem Med Biol 22(3):189–195CrossRefGoogle Scholar
  38. 38.
    Yılmaz S, Ustundag A, Cemiloglu Ulker O, Duydu Y (2016) Protective effect of boric acid on oxidative DNA damage in Chinese hamster lung fibroblast V79 cell lines. Cell J 17(4):748–754PubMedPubMedCentralGoogle Scholar
  39. 39.
    Türkez H, Geyikoğlu F, Tatar A, Keles MS, Kaplan I (2012) The effects of some boron compounds against heavy metal toxicity in human blood. Exp Toxicol Pathol 64:93–101CrossRefGoogle Scholar
  40. 40.
    Ince S, Kücükkurt I, Demirel HH, Acaröz DA, Akbel E, Ciğerci IH (2014) Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats. Chemosphere 108:197–204CrossRefGoogle Scholar
  41. 41.
    Jiang Y, Liu J, Zhou Z, Liu K, Liu C (2018) Fangchinoline protects against renal injury in diabetic nephropathy by modulating the MAPK signaling pathway. Exp Clin Endocrinol Diabetes 126:1–7Google Scholar
  42. 42.
    Castaldo S, Capasso F (2002) Propolis, an old remedy used in modern medicine. Fitoterapia 73:1–6CrossRefGoogle Scholar
  43. 43.
    Kitamura H, Saito N, Fujimoto J, Nakashima KI, Fujikura D (2018) Brazilian propolis ethanol extract and its component kaempferol induce myeloid-derived suppressor cells from macrophages of mice in vivo and in vitro. BMC Complement Altern Med 18(1):138CrossRefGoogle Scholar
  44. 44.
    Frión-Herrera Y, Díaz-García A, Ruiz-Fuentes J, Rodríguez-Sánchez H, Maurício Sforcin J (2018) Mechanisms underlying the cytotoxic effect of propolis on human laryngeal epidermoid carcinoma cells. Nat Prod Res 32(17):2085–2091CrossRefGoogle Scholar
  45. 45.
    Rauch J, Kolch W, Laurent S, Mahmoudi M (2013) Big signals from small particles: regulation of cell signaling pathways by nanoparticles. Chem Rev 113(5):3391–3406CrossRefGoogle Scholar
  46. 46.
    Durick KA, Tomita M, Hunt C, Bradley D (2005) Evidence that boron down-regulates inflammation through the NF-KB pathway. J Federation Am Soc Exp Biol 19(5):A1705Google Scholar
  47. 47.
    Armstrong TA, Spears JW, Lloyd KE (2001) Inflammatory response, growth, andthyroid hormone concentrations are affected by long-term boron supplementation in gilts. J Anim Sci 79:1549–1556CrossRefGoogle Scholar
  48. 48.
    Armstrong TA, Spears JW (2003) Effect of boron supplementation of pig diets on theproduction of tumor necrosis factor-α and interferon-γ. J Anim Sci 81:2552–2561CrossRefGoogle Scholar
  49. 49.
    Fry RS, Brown TT, Lloyd KE, Hansen SL, Legleiter LR, Robarge WP et al (2011) Effect of dietary boron on physiological responses in growing steersinoculated with bovine herpesvirus type-1. Res Vet Sci 90:78–83CrossRefGoogle Scholar
  50. 50.
    Schumer M, Colombel MC, Sawczuk IS, Gobé G, Connor J, O'Toole KM, Olsson CA, Wise GJ, Buttyan R (1992) Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia. Am J Pathol 140(4):831–838PubMedPubMedCentralGoogle Scholar
  51. 51.
    Cornara L, Biagi M, Xiao J, Burlando B (2017) Therapeutic properties of bioactive compounds from different honeybee products. Front Pharmacol 28(8):412CrossRefGoogle Scholar
  52. 52.
    Pérez-Rodríguez M, García-Mendoza E, Farfán-García ED, Das BC, Ciprés-Flores FJ, Trujillo-Ferrara JG, Tamay-Cach F, Soriano-Ursúa MA (2017) Not all boronic acids with a five-membered cycle induce tremor, neuronal damage and decreased dopamine. Neurotoxicology 62:92–99CrossRefGoogle Scholar
  53. 53.
    Ugwu DI, Okoro UC, Ahmad H (2017) New carboxamide derivatives bearing benzenesulphonamide as a selective COX-II inhibitor: design, synthesis and structure-activity relationship. PLoS One 12(9):e018380CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Fatime Geyikoglu
    • 1
  • Kubra Koc
    • 1
    Email author
  • Suat Colak
    • 2
  • Huseyin Serkan Erol
    • 3
  • Salim Cerig
    • 4
  • Berna Kavakcioglu Yardimci
    • 1
    • 5
  • Ozge Cakmak
    • 1
  • Muhammed Bahaeddin Dortbudak
    • 6
  • Gizem Eser
    • 6
  • Ferhunde Aysin
    • 1
    • 7
  • Nihal Simsek Ozek
    • 1
    • 7
  • Serkan Yildirim
    • 5
  1. 1.Department of Biology, Faculty of ScienceAtaturk UniversityErzurumTurkey
  2. 2.Department of Biology, Uzumlu VocationalErzincan UniversityErzincanTurkey
  3. 3.Department of Biochemistry, Faculty of VeterinaryAtaturk UniversityErzurumTurkey
  4. 4.Department of Biotechnology, Faculty of ScienceBartin UniversityBartinTurkey
  5. 5.Department of Chemistry, Faculty of ScienceDokuz Eylül UniversityIzmirTurkey
  6. 6.Department of Pathology, Faculty of VeterinaryAtaturk UniversityErzurumTurkey
  7. 7.East Anatolian High Technology Research and Application Center (DAYTAM)Ataturk UniversityErzurumTurkey

Personalised recommendations