Skip to main content
Log in

Calcium dobesilate prevents cisplatin-induced nephrotoxicity by modulating oxidative and histopathological changes in mice

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Cisplatin is one of the synthetic cancer medicines with nephrotoxicity being one of its major side effects. Past research shows that calcium dobesilate (CaD), as a vascular protective agent in diabetic retinopathy, has antioxidant properties. Thus, this study aims to evaluate the protective effects of CaD in cisplatin-induced nephrotoxicity in mice. A many as 28 mice, in the present experimental research, were randomly distributed into four groups, including control, cisplatin (the intraperitoneal administration of 20 mg/kg cisplatin only on the first day of the experiment), cisplatin + CaD 50 (cisplatin with the oral administration of 50 mg/kg CaD), and cisplatin + CaD 100 (cisplatin with the oral administration of 100 mg/kg CaD). The treated groups received CaD by oral gavage for 4 constitutive days. On the fifth day, the mice were sacrificed, and some biochemical (serum levels of Cr and BUN, renal tissue levels of MDA, and renal activities of SOD and GPx) and pathological parameters were evaluated. Based on the results, there was a significant decrease in the renal SOD and GPx activities; in contrast, there was a significant increase in the BUN, Cr, and renal MDA levels following administering cisplatin. However, the CaD treatment (100 mg/kg) significantly attenuated these alterations. In addition, the kidney’s histological examination of kidneys confirmed the nephroprotective effects of CaD. The findings proved the protective impact of CaD on cisplatin-induced nephrotoxicity by an improvement in the oxidative stress factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Alda O, Valero MS, Pereboom D, Serrano P, Azcona JM, Garay RP (2011) In vitro effect of calcium dobesilate on oxidative/inflammatory stress in human varicose veins. Phlebology 26(8):332–337 Eng

    Article  CAS  Google Scholar 

  • Atessahin A, Yilmaz S, Karahan I, Ceribasi AO, Karaoglu A (2005) Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats. Toxicology 212(2-3):116–123 Eng

    Article  CAS  Google Scholar 

  • Atessahin A, Ceribasi AO, Yuce A, Bulmus O, Cikim G (2007) Role of ellagic acid against cisplatin-induced nephrotoxicity and oxidative stress in rats. Basic Clin Pharmacol Toxicol 100(2):121–126 Eng

    CAS  PubMed  Google Scholar 

  • Bazmandegan G, Amirteimoury M, Kaeidi A, Shamsizadeh A, Khademalhosseini M, Nematollahi MH, Hassanipour M, Fatemi I (2019) Sumatriptan ameliorates renal injury induced by cisplatin in mice. Iran J Basic Med Sci 22(5):563

    PubMed  PubMed Central  Google Scholar 

  • Berthet P, Farine JC, Barras JP (1999) Calcium dobesilate: pharmacological profile related to its use in diabetic retinopathy. Int J Clin Pract 53(8):631–636 Eng

    CAS  PubMed  Google Scholar 

  • Bogdanov P, Solà-Adell C, Hernández C, García-Ramírez M, Sampedro J, Simó-Servat O, Valeri M, Pasquali C, Simó R (2017) Calcium dobesilate prevents the oxidative stress and inflammation induced by diabetes in the retina of db/db mice. J Diabetes Complicat 31(10):1481–1490

    Article  Google Scholar 

  • Boroushaki MT, Rajabian A, Farzadnia M, Hoseini A, Poorlashkari M, Taghavi A, Dolati K, Bazmandegan G (2015) Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat. Ren Fail 37(8):1338–1343

    Article  CAS  Google Scholar 

  • Casanova AG, Hernández-Sánchez MT, López-Hernández FJ, Martínez-Salgado C, Prieto M, Vicente-Vicente L, Morales AI (2020) Systematic review and meta-analysis of the efficacy of clinically tested protectants of cisplatin nephrotoxicity. Eur J Clin Pharmacol 76(1):23–33

    Article  CAS  Google Scholar 

  • Cerrahoglu M, Taner Kurdal A, Iskesen I, Onur E, Sirin H (2009) Calcium dobesilate reduces oxidative stress in cardiac surgery. J Cardiovasc Surg 50(5):695–701 Eng

    CAS  Google Scholar 

  • Chandrasekara N, Shahidi F (2011) Antioxidative potential of cashew phenolics in food and biological model systems as affected by roasting. Food Chem 129(4):1388–1396

    Article  CAS  Google Scholar 

  • Chirino YI, Sanchez-Gonzalez DJ, Martinez-Martinez CM, Cruz C, Pedraza-Chaverri J (2008) Protective effects of apocynin against cisplatin-induced oxidative stress and nephrotoxicity. Toxicology 245(1-2):18–23 Eng

    Article  CAS  Google Scholar 

  • Dasari S, Tchounwou PB (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 740:364–378 Eng

    Article  CAS  Google Scholar 

  • Dehnamaki F, Karimi A, Pilevarian AA, Fatemi I, Hakimizadeh E, Kaeidi A, Allahtavakoli M, Rahmani MR, Khademalhosseini M, Bazmandegan G (2019) Treatment with troxerutin protects against cisplatin-induced kidney injury in mice. Acta Chir Belg 119(1):31–37 Eng

    Article  Google Scholar 

  • Ehsani V, Amirteimoury M, Taghipour Z, Shamsizadeh A, Bazmandegan G, Rahnama A, Khajehasani F, Fatemi I (2017) Protective effect of hydroalcoholic extract of Pistacia vera against gentamicin-induced nephrotoxicity in rats. Ren Fail 39(1):519–525

    Article  CAS  Google Scholar 

  • Gao M, Liu M, Li B, Li M, Bian L, Yu G (2009) Protective effect of calcium dobesilate against early diabetic nephropathy of rat kidney. Yao Xue Xue Bao 44(2):126–133

    CAS  PubMed  Google Scholar 

  • Ghaznavi H, Fatemi I, Kalantari H, Hosseini Tabatabaei SMT, Mehrabani M, Gholamine B, Kalantar M, Mehrzadi S, Goudarzi M (2018) Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats. J Asian Nat Prod Res 20(12):1182–1193

    Article  CAS  Google Scholar 

  • Goudarzi M, Khodayar MJ, Hosseini Tabatabaei SMT, Ghaznavi H, Fatemi I, Mehrzadi S (2017a) Pre-treatment with melatonin protects against cyclophosphamide-induced oxidative stress and renal damage in mice. Fundam Clin Pharmacol 31:602–613

    Google Scholar 

  • Goudarzi M, Khodayar MJ, Hosseini Tabatabaei SMT, Ghaznavi H, Fatemi I, Mehrzadi S (2017b) Pretreatment with melatonin protects against cyclophosphamide-induced oxidative stress and renal damage in mice. Fundam Clin Pharmacol 31(6):625–635

    CAS  PubMed  Google Scholar 

  • Haller H, Ji L, Stahl K, Bertram A, Menne J (2017) Molecular mechanisms and treatment strategies in diabetic nephropathy: new avenues for calcium dobesilate-free radical scavenger and growth factor inhibition. BioMed Res Int 2017:1909258 Eng

    Article  Google Scholar 

  • Hamroun A, Lenain R, Bigna JJ, Speyer E, Bui L, Chamley P, Pottier N, Cauffiez C, Dewaeles E, Dhalluin X (2019) Prevention of cisplatin-induced acute kidney injury: a systematic review and meta-analysis. Drugs 79(14):1567–1582

  • He M, Long P, Guo L, Zhang M, Wang S, He H (2019) Fushiming capsule attenuates diabetic rat retina damage via antioxidation and anti-inflammation. Evid-Based Complement Altern Med 2019:5376439 Eng

    Google Scholar 

  • Hosseinzadeh A, Goudarzi M, Fatemi I, Khodayar MJ, Mehrzadi S, Khalili HR, Karimi MA (2020) Gemfibrozil attenuates doxorubicin induced toxicity in renal tissues of male rats by reducing the oxidative insult and inflammation. Biotech Histochem 95(7):532–539

  • Jafarey M, Ashtiyani SC, Najafi H (2014) Calcium dobesilate for prevention of gentamicin-induced nephrotoxicity in rats. Iran J Kidney Dis 8(1):46–52

  • Kaeidi A, Sahamsizadeh A, Allahtavakoli M, Fatemi I, Rahmani M, Hakimizadeh E, Hassanshahi J (2020a) The effect of oleuropein on unilateral ureteral obstruction induced-kidney injury in rats: the role of oxidative stress, inflammation and apoptosis. Mol Biol Rep 47(2):1371–1379

    Article  CAS  Google Scholar 

  • Kaeidi A, Taghipour Z, Allahtavakoli M, Fatemi I, Hakimizadeh E, Hassanshahi J (2020b) Ameliorating effect of troxerutin in unilateral ureteral obstruction induced renal oxidative stress, inflammation, and apoptosis in male rats. Naunyn Schmiedeberg’s Arch Pharmaco 393(5):879–888

  • Karimi MY, Fatemi I, Kalantari H, Mombeini MA, Mehrzadi S, Goudarzi M (2019) Ellagic acid prevents oxidative stress, inflammation, and histopathological alterations in acrylamide-induced hepatotoxicity in Wistar rats. J Diet Suppl 17(6):1–12

  • Liu C-M, Ma J-Q, Lou YJF (2010) Chronic administration of troxerutin protects mouse kidney against D-galactose-induced oxidative DNA damage. Food Chem Toxicol 48(10):2809–2817

  • Mehrzadi S, Fatemi I, Esmaeilizadeh M, Ghaznavi H, Kalantar H, Goudarzi M (2018a) Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats. Biomed Pharmacother 97:233–239 Eng

    Article  CAS  Google Scholar 

  • Mehrzadi S, Fatemi I, Malayeri AR, Khodadadi A, Mohammadi F, Mansouri E, Rashno M, Goudarzi M (2018b) Ellagic acid mitigates sodium arsenite-induced renal and hepatic toxicity in male Wistar rats. Pharmacol Rep 70(4):712–719

    Article  CAS  Google Scholar 

  • Ozkok A, Edelstein CL (2014) Pathophysiology of cisplatin-induced acute kidney injury. Biomed Res Int 2014:e967826

  • Priyamvada S, Priyadarshini M, Arivarasu N, Farooq N, Khan S, Khan SA, Khan MW, Yusufi A (2008) Studies on the protective effect of dietary fish oil on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Prostaglandins Leukot Essent Fat Acids 78(6):369–381

    Article  CAS  Google Scholar 

  • Qin L, Qin W, Wang J, Lin L (2017) Combined treatment of diabetic nephropathy with alprostadil and calcium dobesilate, Exp Ther Med. 14(5):5012–5016 Eng

  • Rasoulian B, Kaeidi A, Pourkhodadad S, Dezfoulian O, Rezaei M, Wahhabaghai H, Alirezaei M (2014) Effects of pretreatment with single-dose or intermittent oxygen on Cisplatin-induced nephrotoxicity in rats. Nephrourol Mon 6(5):e19680

  • Rota R, Chiavaroli C, Garay RP, Hannaert P (2004) Reduction of retinal albumin leakage by the antioxidant calcium dobesilate in streptozotocin-diabetic rats. Eur J Pharmacol 495(2–3):217–224

  • Saleh S, El-Demerdash E (2005) Protective effects of L-arginine against cisplatin-induced renal oxidative stress and toxicity: role of nitric oxide. Basic Clin Pharmacol Toxicol 97(2):91–97 Eng

    Article  CAS  Google Scholar 

  • Sharp CN, Siskind LJ (2017) Developing better mouse models to study cisplatin-induced kidney injury. Am J Physiol Renal Physiol 313(4):835–841

  • Solà-Adell C, Bogdanov P, Hernández C, Sampedro J, Valeri M, Garcia-Ramirez M, Pasquali C, Simó R (2017) Calcium dobesilate prevents neurodegeneration and vascular leakage in experimental diabetes. Curr Eye Res 42(9):1273–1286

  • Taghipour Z, Kaviani E, Kaeidi A, Shamsizadeh A, Fatemi I (2019) Atorvastatin attenuates D-galactose-induced hepatorenal toxicity in mice: an experimental study with histopathological evaluations. Physiol Pharmacol 23(1):36–43

  • Unal Y, Tuncal S, Kosmaz K, Kucuk B, Kismet K, Cavusoglu T, Celepli P, Senes M, Yildiz S, Hucumenoglu S (2019) The effect of calcium dobesilate on liver damage in experimental obstructive jaundice. J Invest Surg 32(3):238–244 Eng

    Article  Google Scholar 

  • Yao X, Panichpisal K, Kurtzman N, Nugent K (2007) Cisplatin nephrotoxicity: a review. Am J Med Sci 334(2):115–124

  • Zhang X, Liu W, Wu S, Jin J, Li W, Wang NJSCLS (2015) Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis. Sci China Life Sci 58(1):101–107

Download references

Acknowledgments

The authors would like to extend their thanks to the clinical research development unit in Ali-Ibn Abi-Talib Hospital, Rafsanjan University of Medical Sciences, for its support and collaboration.

Funding

This article is based on Dr. Ali Fathinejad’s thesis for obtaining a degree in general medicine from Rafsanjan University of Medical Sciences with Grant Number 97062.

Author information

Authors and Affiliations

Authors

Contributions

Conceived and designed the experiments: GB and MA. Performed the experiments: BG, AK, MK, and AF. Analyzed the data: GB and MA. Contributed reagents/materials/analysis tools: AK, GB, and IF. Wrote the paper: IF and GB. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Morteza Amirteimoury.

Ethics declarations

All experiments were performed in accordance with the guidelines set by the ethical committee under ethics code IR.RUMS.REC.1397.028.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PZFX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bazmandegan, G., Fatemi, I., Kaeidi, A. et al. Calcium dobesilate prevents cisplatin-induced nephrotoxicity by modulating oxidative and histopathological changes in mice. Naunyn-Schmiedeberg's Arch Pharmacol 394, 515–521 (2021). https://doi.org/10.1007/s00210-020-01990-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-020-01990-3

Keywords

Navigation