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Clinical Cancer Drugs

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ISSN (Print): 2212-697X
ISSN (Online): 2212-6988

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Research Article

Coenzyme Q10 Attenuates Cisplatin-induced Nephrotoxicity Through Counteracting Oxidative Stress and Inflammation

Author(s): Hala S. Bash and Ihsan S. Rabeea*

Volume 6, Issue 1, 2019

Page: [41 - 47] Pages: 7

DOI: 10.2174/2212697X06666190701113043

Abstract

Background: Cisplatin is an anticancer drug used in the management of solid tumors, however, dose-related nephrotoxicity is one of its major problems. Agents having antioxidants, antiinflammatory and/or antiapoptotic activities may thus represent potential therapeutic options to avoid cisplatin-induced nephrotoxicity. Among these agents, coenzyme Q10 has several pharmacological properties including antioxidant, anti-inflammatory and/or anti-apoptotic effects.

Objective: The current study aimed to examine whether coenzyme Q10 could attenuate cisplatininduced nephrotoxicity or not.

Methods: 24 adult rats were randomly separated into three groups (8 rats per group). The first one was the control group, rats receiving vehicle (olive oil) intraperitoneally. The second group was Cisplatin treated group, rats were receiving 13 mg/kg of Cisplatin intraperitoneally as a single dose. The third group (Cisplatin + Coenzyme Q10), rats were receiving 13 mg/kg as a single intraperitoneal dose of Cisplatin and coenzyme Q10 daily for six consecutive days (10 mg/kg intraperitoneally).

Results: Cisplatin caused significant increases in serum creatinine and severe histological lesions. Cisplatin treated group also showed a significant elevation in renal malondialdehyde concentration as a marker of oxidative stress; renal tumor necrosis factor-alpha concentration as a marker of inflammation; and Kidney injury molecule -1 concentration. Coenzyme Q10 significantly attenuated cisplatininduced nephrotoxicity through lowering serum creatinine and improving nephrotoxicity histological scores. Coenzyme Q10 also significantly reduced the renal concentration of MDA, TNF-α and KIM-1 relative to cisplatin treated group.

Conclusions: Coenzyme Q10 has a potential nephroprotective effect against cisplatin-induced nephrotoxicity that was demonstrated by biochemical and histopathological analysis.

Keywords: Cisplatin, renal toxicity, KIM-1, TNF-α, CoQ10, oxidative stress.

Graphical Abstract

[1]
Eljack ND, Ma H-YM, Drucker J, et al. Mechanisms of cell uptake and toxicity of the anticancer drug cisplatin. Metallomics 2014; 6(11): 2126-33.
[http://dx.doi.org/10.1039/C4MT00238E] [PMID: 25306996]
[2]
Momeni A, Hajigholami A, Geshnizjani S, Kheiri S. Effect of silymarin in the prevention of Cisplatin nephrotoxicity, a clinical trial study. J Clin Diagn Res 2015; 9(4): OC11-3.
[http://dx.doi.org/10.7860/JCDR/2015/12776.5789] [PMID: 26046020]
[3]
Chtourou Y, Aouey B, Kebieche M, Fetoui H. Protective role of naringin against cisplatin induced oxidative stress, inflammatory response and apoptosis in rat striatum via suppressing ROS-mediated NF-κB and P53 signaling pathways. Chem Biol Interact 2015; 239: 76-86.
[http://dx.doi.org/10.1016/j.cbi.2015.06.036] [PMID: 26120027]
[4]
Tomar A, Vasisth S, Khan SI, et al. Galangin ameliorates cisplatin induced nephrotoxicity in vivo by modulation of oxidative stress, apoptosis and inflammation through interplay of MAPK signaling cascade. Phytomedicine 2017; 34: 154-61.
[http://dx.doi.org/10.1016/j.phymed.2017.05.007] [PMID: 28899498]
[5]
Domitrović R, Cvijanović O, Pernjak-Pugel E, Škoda M, Mikelić L, Crnčević-Orlić Z. Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis. Food Chem Toxicol 2013; 62: 397-406.
[http://dx.doi.org/10.1016/j.fct.2013.09.003] [PMID: 24025684]
[6]
Laredj LN, Licitra F, Puccio HM. The molecular genetics of coenzyme Q biosynthesis in health and disease. Biochimie 2014; 100: 78-87.
[http://dx.doi.org/10.1016/j.biochi.2013.12.006] [PMID: 24355204]
[7]
Eftekhari A, Ahmadian E, Azarmi Y, Parvizpur A, Hamishehkar H, Eghbal MA. In vitro/vivo studies towards mechanisms of risperidone-induced oxidative stress and the protective role of coenzyme Q10 and N- acetylcysteine. Toxicol Mech Methods 2016; 26(7): 520-8.
[8]
Mirmalek SA, Gholamrezaei BA, Yavari H, et al. Antioxidant and anti-inflammatory effects of coenzyme Q10 on L-arginine-induced acute pancreatitis in rat. Oxid Med Cell Longev 2016; 20165818479
[http://dx.doi.org/10.1155/2016/5818479] [PMID: 27190575]
[9]
El-Sheikh AAK, Morsy MA, Mahmoud MM, Rifaai RA, Abdelrahman AM. Effect of coenzyme-Q10 on doxorubicin-induced nephrotoxicity in rats. Adv Pharmacol Sci 2012; 981461: 1-8.
[10]
Humanes B, Lazaro A, Camano S, et al. Cilastatin protects against cisplatin-induced nephrotoxicity without compromising its anticancer efficiency in rats. Kidney Int 2012; 82(6): 652-63.
[http://dx.doi.org/10.1038/ki.2012.199] [PMID: 22718191]
[11]
Ekinci Akdemir FN, Albayrak M, Çalik M, Bayir Y, Gülçin İ. The protective effects of p-coumaric acid on acute liver and kidney damages induced by cisplatin. Biomedicines 2017; 5(2): 18.
[http://dx.doi.org/10.3390/biomedicines5020018] [PMID: 28536361]
[12]
Salama AS. Are mice and rats good experimental models to explore novel compounds against cisplatin induced nephrotoxicity? Int J Nephrol Kidney Failure 2015; 1(2)
[http://dx.doi.org/10.16966/2380-5498.107]
[13]
Domitrović R, Potočnjak I, Crnčević-Orlić Z, Škoda M. Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice Food Chem Toxicol 2014; 66: 321-8.
[http://dx.doi.org/10.1016/j.fct.2014.02.002] [PMID: 24518541]
[14]
Shaker RA, Abboud SH, Assad HC, Hadi N. Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. BMC Pharmacol Toxicol 2018; 19(1): 3.
[http://dx.doi.org/10.1186/s40360-017-0184-z] [PMID: 29321061]
[15]
Fouad AA, Al-Sultan AI, Refaie SM, Yacoubi MT. Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice. Toxicology 2010; 274(1-3): 49-56.
[http://dx.doi.org/10.1016/j.tox.2010.05.007] [PMID: 20510337]
[16]
Hussein AA, Assad HC, Rabeea IS. Antihyperlipidemic, antioxidant and anti-inflammatory effects of ginkgo biloba in high cholesterol fed rabbits. J Pharm Sci Res 2017; 9(11): 2163-7.
[17]
Verma PK, Raina R, Sultana M, Singh M, Kumar P. Total antioxidant and oxidant status of plasma and renal tissue of cisplatin-induced nephrotoxic rats: protection by floral extracts of Calendula officinalis Linn. Ren Fail 2016; 38(1): 142-50.
[http://dx.doi.org/10.3109/0886022X.2015.1103585] [PMID: 26513373]
[18]
Ross MH, Reith EJ, Romrell LJ. Histology-A Text and Atlas (ki sp k). Baltimore, MD: Williams and Wilkins 1981.
[19]
Forgionne GA, Hoenjet KM, Dagnelie PC, et al. Bovine cartilage, coenzyme Q10, and wheat grass therapy for primary peritoneal cancer. J Altern Complement Med 2005; 11(1): 161-5.
[http://dx.doi.org/10.1089/acm.2005.11.161] [PMID: 15750376]
[20]
Hertz N, Lister RE. Improved survival in patients with end-stage cancer treated with coenzyme Q10 and other antioxidants: A pilot study. J Int Med Res 2009; 37: 1961-71.
[21]
Soni A, Verma M, Kaushal V, Ghalaut V. Coenzyme Q10 therapy in current clinical practice. Int J Res Med Sci 2015; 3(4): 817-25.
[http://dx.doi.org/10.5455/2320-6012.ijrms20150401]
[22]
Mercantepe F, Mercantepe T, Topcu A, Yılmaz A, Tumkaya L. Protective effects of amifostine, curcumin, and melatonin against cisplatin-induced acute kidney injury. Naunyn Schmiedebergs Arch Pharmacol 2018; 391(9): 915-31.
[http://dx.doi.org/10.1007/s00210-018-1514-4] [PMID: 29860655]
[23]
Manohar S, Leung N. Cisplatin nephrotoxicity : A review of the literature 2017.
[24]
Ilić S, Stojiljković N, Veljković M, Veljković S, Stojanović G. Protective effect of quercetin on cisplatin-induced nephrotoxicity in rats. Igaku To Seibutsugaku 2014; 16(2): 71-5.
[25]
Sharma A, Patnai P, Mehta N, Dalwadi P. Effect of coenzyme Q10 alone and it’s combination with pentoxifylline in cisplatin-induced nephrotoxicity in rats. J Pharm Sci Bioscientific Res 2016; 6(6): 790-800.
[26]
Dasari S, Bernard Tchounwou P. Cisplatin in cancer therapy : Molecular mechanisms of action. Eur J Pharmacol 2014; 1-15.
[27]
Zirak MR, Rahimian R, Ghazi-Khansari M, et al. Tropisetron attenuates cisplatin-induced nephrotoxicity in mice. Eur J Pharmacol 2014; 738: 222-9.
[http://dx.doi.org/10.1016/j.ejphar.2014.05.050] [PMID: 24905858]
[28]
Kilic U, Kilic E, Tuzcu Z, et al. Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway. Nutr Metab (Lond) 2013; 10(1): 7.
[http://dx.doi.org/10.1186/1743-7075-10-7] [PMID: 23311701]
[29]
Helmy MM, Hashim AA, Mouneir SM. Zileuton alleviates acute cisplatin nephrotoxicity: Inhibition of lipoxygenase pathway favorably modulates the renal oxidative/inflammatory/caspase-3 axis. Prostaglandins Other Lipid Mediat 2018; 135: 1-10.
[http://dx.doi.org/10.1016/j.prostaglandins.2018.01.001] [PMID: 29355720]
[30]
Gluba A, Banach M, Hannam S, Mikhailidis DP, Sakowicz A, Rysz J. The role of Toll-like receptors in renal diseases. Nat Rev Nephrol 2010; 6(4): 224-35.
[http://dx.doi.org/10.1038/nrneph.2010.16] [PMID: 20177402]
[31]
Ma X, Yan L, Zhu Q, Shao F. Puerarin attenuates cisplatin-induced rat nephrotoxicity: The involvement of TLR4/NF-κB signaling pathway. PLoS One 2017; 12(2)e0171612
[http://dx.doi.org/10.1371/journal.pone.0171612] [PMID: 28182789]
[32]
Hagar H, Medany A, El Salam R, Medany G, El Nayal OA. Betaine supplementation mitigates cisplatin-induced nephrotoxicity by abrogation of oxidative/nitrosative stress and suppression of inflammation and apoptosis in rats. Experimental and Toxicologic Pathology. Elsevier GmbH 2014; pp. 1-9.

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