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Protective Effect of Hesperidin on Sodium Arsenite-Induced Nephrotoxicity and Hepatotoxicity in Rats

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Abstract

The present study was conducted to investigate the protective effects of hesperidin (HSP) against sodium arsenite (SA)-induced nephrotoxicity and hepatotoxicity in rats. Thirty-five male Sprague Dawley rats were divided into five groups as follows: control, HSP, SA, SA + HSP 100, and SA + HSP 200. Rats were orally gavaged with SA (10 mg/kg body weight) and HSP (100 and 200 mg/kg body weight) for 15 days. SA increased oxidative damage by decreasing antioxidant enzyme activities, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and glutathione (GSH) level and increasing malondialdehyde (MDA) level in the kidney and liver tissues. In addition, it increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and serum urea and creatinine levels. Furthermore, SA caused inflammation, apoptosis, and oxidative DNA damage by increasing tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), cysteine aspartate-specific protease-3 (caspase-3), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in the kidney and liver tissues and by increasing liver p53 and kidney interleukin-6 (IL-6) expressions. In other words, HSP administration reduced apoptosis, oxidative stress, inflammation, and oxidative DNA damage significantly in SA-induced kidney and liver tissues depending on dose. In this study, it was seen that HSP showed a protective effect against SA-induced kidney and liver toxicity.

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References

  1. El-Demerdash FM, Yousef MI, Radwan FME (2009) Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs. Food Chem Toxicol 47:249–254. https://doi.org/10.1016/j.fct.2008.11.013

    Article  CAS  PubMed  Google Scholar 

  2. Akanda MR, Tae HJ, Kim IS et al (2017) Hepatoprotective role of Hydrangea macrophylla against sodium arsenite-induced mitochondrial-dependent oxidative stress via the inhibition of MAPK/caspase-3 pathways. Int J Mol Sci 18:1482. https://doi.org/10.3390/ijms18071482

    Article  CAS  PubMed Central  Google Scholar 

  3. Saha S, Rashid K, Sadhukhan P et al (2016) Attenuative role of mangiferin in oxidative stress-mediated liver dysfunction in arsenic-intoxicated murines. BioFactors 42:515–532. https://doi.org/10.1002/biof.1276

    Article  CAS  PubMed  Google Scholar 

  4. Fouad AA, Al-Mulhim AS, Jresat I (2012) Telmisartan treatment attenuates arsenic-induced hepatotoxicity in mice. Toxicology 300:149–157. https://doi.org/10.1016/j.tox.2012.06.015

    Article  CAS  PubMed  Google Scholar 

  5. Dash M, Maity M, Dey A et al (2018) The consequence of NAC on sodium arsenite-induced uterine oxidative stress. Toxicol Reports 5:278–287. https://doi.org/10.1016/j.toxrep.2018.02.003

    Article  CAS  Google Scholar 

  6. Adil M, Kandhare AD, Visnagri A, Bodhankar SL (2015) Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, caspase-3, TGF-β, and TNF-α. Ren Fail 37:1396–1407. https://doi.org/10.3109/0886022X.2015.1074462

    Article  CAS  PubMed  Google Scholar 

  7. Kim Y-J, Kim J-M (2015) Arsenic toxicity in male reproduction and development. Dev Reprod 19:167–180. https://doi.org/10.12717/DR.2015.19.4.167

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lin A, Zhang X, Zhu Y-G, Zhao F-J (2008) Arsenate-induced toxicity: effects on antioxidative enzymes and DNA damage in Vicia faba. Environ Toxicol Chem 27:413. https://doi.org/10.1897/07-266R.1

    Article  CAS  PubMed  Google Scholar 

  9. Gülçin İ (2012) Antioxidant activity of food constituents: an overview. Arch Toxicol 86:345–391. https://doi.org/10.1007/s00204-011-0774-2

    Article  CAS  Google Scholar 

  10. Kandemir FM, Kucukler S, Eldutar E, et al (2017) Chrysin protects rat kidney from paracetamol-induced oxidative stress, inflammation, apoptosis, and autophagy: a multi-biomarker approach. Sci Pharm 85. doi: https://doi.org/10.3390/scipharm85010004

  11. Kandemir FM, Ozkaraca M, Küçükler S et al (2017) Preventive effects of hesperidin on diabetic nephropathy induced by streptozotocin via modulating TGF-β1 and oxidative DNA damage. Toxin Rev:1–7. https://doi.org/10.1080/15569543.2017.1364268

  12. Taslimi P, Caglayan C, Gulcin İ (2017) The impact of some natural phenolic compounds on carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α-glycosidase enzymes: an antidiabetic, anticholinergic, and antiepileptic study. J Biochem Mol Toxicol 31:e21995. https://doi.org/10.1002/jbt.21995

    Article  CAS  Google Scholar 

  13. Mishra K (2013) Structure-activity relationship of antioxidative property of hesperidin. Int J Pharm Erud 2:40

    Google Scholar 

  14. Hamdy SM, Shabaan AM, Abdel Latif AKM et al (2017) Protective effect of hesperidin and tiger nut against acrylamide toxicity in female rats. Exp Toxicol Pathol 69:580–588. https://doi.org/10.1016/j.etp.2017.05.004

    Article  CAS  PubMed  Google Scholar 

  15. Ahmad ST, Arjumand W, Nafees S (2012) Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation. Toxicol Lett 208:149–161. https://doi.org/10.1016/j.toxlet.2011.10.023

    Article  CAS  PubMed  Google Scholar 

  16. Placer ZA, Cushman LL, Johnson BC (1966) Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem 16:359–364. https://doi.org/10.1016/0003-2697(66)90167-9

    Article  CAS  PubMed  Google Scholar 

  17. Aebi H (1983) Catalase. Methods Enzym Anal 3:273

    CAS  Google Scholar 

  18. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  20. Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958. https://doi.org/10.1016/0006-291X(76)90747-6

    Article  CAS  PubMed  Google Scholar 

  21. Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  22. Majhi CR, Khan S, Leo MDM et al (2011) Effects of acetaminophen on reactive oxygen species and nitric oxide redox signaling in kidney of arsenic-exposed rats. Food Chem Toxicol 49:974–982. https://doi.org/10.1016/j.fct.2011.01.003

    Article  CAS  PubMed  Google Scholar 

  23. Yousef MI, El-Demerdash FM, Radwan FME (2008) Sodium arsenite induced biochemical perturbations in rats: ameliorating effect of curcumin. Food Chem Toxicol 46:3506–3511. https://doi.org/10.1016/J.FCT.2008.08.031

    Article  CAS  PubMed  Google Scholar 

  24. Brunati AM, Pagano MA, Bindoli A, Rigobello MP (2010) Thiol redox systems and protein kinases in hepatic stellate cell regulatory processes. Free Radic Res 44:363–378. https://doi.org/10.3109/10715760903555836

    Article  CAS  PubMed  Google Scholar 

  25. Mershiba SD, Dassprakash MV, Saraswathy SD (2013) Protective effect of naringenin on hepatic and renal dysfunction and oxidative stress in arsenic intoxicated rats. Mol Biol Rep 40:3681–3691. https://doi.org/10.1007/s11033-012-2444-8

    Article  CAS  PubMed  Google Scholar 

  26. Flora SJS (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51:257–281. https://doi.org/10.1016/j.freeradbiomed.2011.04.008

    Article  CAS  PubMed  Google Scholar 

  27. Maiti S, Chatterjee AK (2001) Effects on levels of glutathione and some related enzymes in tissues after an acute arsenic exposure in rats and their relationship to dietary protein deficiency. Arch Toxicol 75:531–537

    Article  CAS  PubMed  Google Scholar 

  28. Flora SJS, Chouhan S, Kannan GM et al (2008) Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats. Oxidative Med Cell Longev 1:39–45

    Article  Google Scholar 

  29. Mishra D, Mehta A, Flora SJS (2008) Reversal of arsenic-induced hepatic apoptosis with combined administration of DMSA and its analogues in guinea pigs: role of glutathione and linked enzymes. Chem Res Toxicol 21:400–407. https://doi.org/10.1021/tx700315a

    Article  CAS  PubMed  Google Scholar 

  30. Shi H, Shi X, Liu KJ (2004) Oxidative mechanism of arsenic toxicity and carcinogenesis. Mol Cell Biochem 255:67–78. https://doi.org/10.1023/B:MCBI.0000007262.26044.e8

    Article  CAS  PubMed  Google Scholar 

  31. Kirici M, Turk C, Caglayan C, Kirici M (2017) Toxic effects of copper sulphate pentahydrate on antioxidant enzyme activities and lipid peroxidation of freshwater fish Capoeta umbla (Heckel, 1843) tissues. Appl Ecol Environ Res 15:1685–1696

    Article  Google Scholar 

  32. Ogun M, Ozcan A, Karaman M et al (2016) Oleuropein ameliorates arsenic induced oxidative stress in mice. J Trace Elem Med Biol 36:1–6. https://doi.org/10.1016/j.jtemb.2016.03.006

    Article  CAS  PubMed  Google Scholar 

  33. Kandemir FM, Küçükler S, Çağlayan C (2017) Beneficial effects of silymarin and naringin against methotrexate-induced hepatotoxicity in rats. Bil Derg 12:167–177. https://doi.org/10.17094/ataunivbd.347970

    Article  Google Scholar 

  34. El-Maraghy SA, Rizk SM, El-Sawalhi MM (2009) Hepatoprotective potential of crocin and curcumin against iron overload-induced biochemical alterations in rat. Afr J Biochem Res 3:215–221

    CAS  Google Scholar 

  35. Pari L, Karthikeyan A, Karthika P, Rathinam A (2015) Protective effects of hesperidin on oxidative stress, dyslipidaemia and histological changes in iron-induced hepatic and renal toxicity in rats. Toxicol Reports 2:46–55. https://doi.org/10.1016/j.toxrep.2014.11.003

    Article  CAS  Google Scholar 

  36. Kandemir FM, Yildirim S, Kucukler S et al (2018) Therapeutic efficacy of zingerone against vancomycin-induced oxidative stress, inflammation, apoptosis and aquaporin 1 permeability in rat kidney. Biomed Pharmacother 105:981–991. https://doi.org/10.1016/j.biopha.2018.06.048

    Article  CAS  PubMed  Google Scholar 

  37. Jagadeesan G, Bharathi E (2014) In vivo restoration of hepatic and nephro protective potential of hesperidin and ellagic acid against mercuric chloride intoxicated rats. Biomed Aging Pathol 4:219–222. https://doi.org/10.1016/j.biomag.2014.01.008

    Article  CAS  Google Scholar 

  38. Roussel RR, Barchowsky A (2000) Arsenic inhibits NF-κB-mediated gene transcription by blocking IκB kinase activity and IκBα phosphorylation and degradation. Arch Biochem Biophys 377:204–212. https://doi.org/10.1006/ABBI.2000.1770

    Article  CAS  PubMed  Google Scholar 

  39. Benzer F, Kandemir FM, Kucukler S et al (2018) Chemoprotective effects of curcumin on doxorubicin-induced nephrotoxicity in Wistar rats: by modulating inflammatory cytokines, apoptosis, oxidative stress and oxidative DNA damage. Arch Physiol Biochem 0:1–10. https://doi.org/10.1080/13813455.2017.1422766

    Article  CAS  Google Scholar 

  40. Kandemir FM, Kucukler S, Caglayan C et al (2017) Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties. J Food Biochem 41:e12398. https://doi.org/10.1111/jfbc.12398

    Article  CAS  Google Scholar 

  41. Jing H, Shen G, Wang G et al (2012) MG132 alleviates liver injury induced by intestinal ischemia/reperfusion in rats: involvement of the AhR and NFκB pathways. J Surg Res 176:63–73. https://doi.org/10.1016/j.jss.2011.09.001

    Article  CAS  PubMed  Google Scholar 

  42. Ruiz-Ramos R, Lopez-Carrillo L, Rios-Perez AD et al (2009) Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-κB activation and cell proliferation in human breast cancer MCF-7 cells. Mutat Res Toxicol Environ Mutagen 674:109–115. https://doi.org/10.1016/j.mrgentox.2008.09.021

    Article  CAS  Google Scholar 

  43. Eldutar E, Kandemir FM, Kucukler S, Caglayan C (2017) Restorative effects of Chrysin pretreatment on oxidant-antioxidant status, inflammatory cytokine production, and apoptotic and autophagic markers in acute paracetamol-induced hepatotoxicity in rats: an experimental and biochemical study. J Biochem Mol Toxicol 31:e21960. https://doi.org/10.1002/jbt.21960

    Article  CAS  Google Scholar 

  44. Donnahoo KK, Shames BD, Harken AH, Meldrum DR (1999) Review article: the role of tumor necrosis factor in renal ischemia-reperfusion injury. J Urol 162:196–203. https://doi.org/10.1097/00005392-199907000-00068

    Article  CAS  PubMed  Google Scholar 

  45. Bae Y, Lee S, Kim S-H (2011) Chrysin suppresses mast cell-mediated allergic inflammation: involvement of calcium, caspase-1 and nuclear factor-κB. Toxicol Appl Pharmacol 254:56–64. https://doi.org/10.1016/j.taap.2011.04.008

    Article  CAS  PubMed  Google Scholar 

  46. Adil M, Visnagri A, Shiva Kuma V et al (2014) Protective effect of naringin on sodium arsenite induced testicular toxicity via modulation of biochemical perturbations in experimental rats. Pharmacologia 5:222–234. https://doi.org/10.5567/pharmacologia.2014.222.234

    Article  CAS  Google Scholar 

  47. Bali İ, Bilir B, Emir S et al (2016) The effects of melatonin on liver functions in arsenic-induced liver damage. Ulus cerrahi Derg 32:233–237. https://doi.org/10.5152/UCD.2015.3224

    Article  PubMed  PubMed Central  Google Scholar 

  48. Ola MS, Nawaz M, Ahsan H (2011) Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 351:41–58. https://doi.org/10.1007/s11010-010-0709-x

    Article  CAS  PubMed  Google Scholar 

  49. Othman MS, Safwat G, Aboulkhair M, Abdel Moneim AE (2014) The potential effect of berberine in mercury-induced hepatorenal toxicity in albino rats. Food Chem Toxicol 69:175–181. https://doi.org/10.1016/j.fct.2014.04.012

    Article  CAS  PubMed  Google Scholar 

  50. Wang B, Xiao Z, Ko HL, Ren E-C (2010) The p53 response element and transcriptional repression. Cell Cycle 9:870–879. https://doi.org/10.4161/cc.9.5.10825

    Article  CAS  PubMed  Google Scholar 

  51. Chen J, Wang J, Li H et al (2016) p53 activates miR-192-5p to mediate vancomycin induced AKI. Sci Rep 6:38868. https://doi.org/10.1038/srep38868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chou R-H, Huang H (2002) Restoration of p53 tumor suppressor pathway in human cervical carcinoma cells by sodium arsenite. Biochem Biophys Res Commun 293:298–306. https://doi.org/10.1016/S0006-291X(02)00212-7

    Article  CAS  PubMed  Google Scholar 

  53. Vogt BL, Rossman TG (2001) Effects of arsenite on p53, p21 and cyclin D expression in normal human fibroblasts—a possible mechanism for arsenite’s comutagenicity. Mutat Res 478:159–168

    Article  CAS  PubMed  Google Scholar 

  54. Ueno M, Masutani H, Arai RJ et al (1999) Thioredoxin-dependent redox regulation of p53-mediated p21 activation. J Biol Chem 274:35809–35815

    Article  CAS  PubMed  Google Scholar 

  55. Benzer F, Kandemir FM, Ozkaraca M, et al (2018) Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats. J Biochem Mol Toxicol 32. doi: https://doi.org/10.1002/jbt.22030

  56. Kaygusuzoglu E, Caglayan C, Kandemir FM et al (2018) Zingerone ameliorates cisplatin-induced ovarian and uterine toxicity via suppression of sex hormone imbalances, oxidative stress, inflammation and apoptosis in female Wistar rats. Biomed Pharmacother 102:517–530. https://doi.org/10.1016/j.biopha.2018.03.119

    Article  CAS  PubMed  Google Scholar 

  57. Banerjee N, Banerjee M, Ganguly S et al (2008) Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individuals. Toxicology 246:101–111. https://doi.org/10.1016/j.tox.2007.12.029

    Article  CAS  PubMed  Google Scholar 

  58. Cetin AA, Çetin A, Çiftçi O, Otlu A (2016) Protective effect of hesperidin on oxidative and histological liver damage following carbon tetrachloride administration in Wistar rats. Arch Med Sci 12:486–493. https://doi.org/10.5114/aoms.2015.49484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sahu BD, Kuncha M, Sindhura GJ, Sistla R (2013) Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage. Phytomedicine 20:453–460. https://doi.org/10.1016/j.phymed.2012.12.001

    Article  CAS  PubMed  Google Scholar 

  60. Pan H, Zhang L, Guo M et al (2010) The oxidative stress status in diabetes mellitus and diabetic nephropathy. Acta Diabetol 47:71–76. https://doi.org/10.1007/s00592-009-0128-1

    Article  CAS  PubMed  Google Scholar 

  61. Caglayan C, Temel Y, Kandemir FM et al (2018) Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environ Sci Pollut Res:1–17. https://doi.org/10.1007/s11356-018-2242-5

  62. Sinha D, Roy M (2011) Antagonistic role of tea against sodium arsenite-induced oxidative DNA damage and inhibition of DNA repair in Swiss Albino mice. J Environ Pathol Toxicol Oncol 30:311–322. https://doi.org/10.1615/JEnvironPatholToxicolOncol.v30.i4.40

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by the Unit of Scientific Research Projects of the University of Ağrı İbrahim Çeçen (Project number ECZF.17.002).

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Authors and Affiliations

  1. Department of Pharmacy Professional Sciences, Faculty of Pharmacy, Agri Ibrahim Cecen University, 04100, Ağrı, Turkey

    Erdinç Turk

  2. Department of Biochemistry, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey

    Fatih Mehmet Kandemir & Sefa Kucukler

  3. Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey

    Serkan Yildirim

  4. Department of Biochemistry, Faculty of Veterinary Medicine, Bingol University, Bingol, Turkey

    Cuneyt Caglayan

  5. Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Agri Ibrahim Cecen University, Agri, Turkey

    Muslum Kuzu

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  1. Erdinç Turk
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Correspondence to Erdinç Turk.

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Turk, E., Kandemir, F.M., Yildirim, S. et al. Protective Effect of Hesperidin on Sodium Arsenite-Induced Nephrotoxicity and Hepatotoxicity in Rats. Biol Trace Elem Res 189, 95–108 (2019). https://doi.org/10.1007/s12011-018-1443-6

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