Coenzyme Q10 and resveratrol protect against paclitaxel-induced nephrotoxicity in rats

Document Type : Original Article

Authors

1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Nigeria

2 Department of Pharmacology/Toxicology. Faculty of Pharmacy, Niger Delta University, Bayelsa State, Nigeria

Abstract

The clinical use of paclitaxel (PCL) may cause nephrotoxicity. Antioxidants have shown potential benefits in some disease conditions. This study examined the protective abilities of coenzyme Q10 (CoQ10) and resveratrol (RSV) against PCL-induced nephrotoxicity in albino rats. Adult male albino rats (n=45) were divided into 9 groups of n=5. The rats were supplemented orally with CoQ10 (20mg/kg), RSV (20mg/kg) and CoQ10+RSV (ip) daily for 5 days respectively before the administration a dose of PCL (20mg/kg) i.p on day 5. The rats were euthanized; blood samples were collected and assessed for serum biochemical markers. Kidneys were assessed for melondialdehyde, antioxidants (superoxide dismutase, glutathione, glutathione peroxidase and catalase) and histology. Body and kidney weights were normal (p>0.05) in PCL administered rats when compared to control. Serum total protein, albumin, potassium, chloride, sodium, bicarbonate and kidney malondialdehyde levels were significantly (p <0.001) decreased whereas serum creatinine, urea, uric acid and kidney antioxidants levels were significantly (p <0.001) increased in PCL administered rats when compared to control. Hypercellular glomerulus with mesangial proliferation and tubular necrosis were observed in the kidneys of PCL administered rats. However, the aforementioned alterations were significantly reversed in CoQ10 (p <0.05), RSV (p <0.01) and CoQ10+RSV (p <0.001) supplemented rats when compared to PCL. Conclusion: CoQ10 and RSV may clinically protect against PCL-induced nephrotoxicity

Keywords


1. Pizzino G, Irrera N, Cucinotta M, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763. doi:10.1155/2017/8416763
2. Palipoch S. A review of oxidative stress in acute kidney injury: protective role of medicinal plants-derived antioxidants. Afr J Tradit Complement Altern Med. 2013;10(4):88-93. Published 2013 May 16. doi:10.4314/ajtcam.v10i4.15
3. Ozbek E. Devil's Triangle in Kidney Diseases: Oxidative Stress, Mediators, and Inflammation Induction of Oxidative Stress in Kidney, Int J Nephrol. 2012; Volume 2012, 465897, 1-9
4. Barnett LMA, Cummings BS. Nephrotoxicity and Renal Pathophysiology: A Contemporary Perspective. Toxicol Sci. 2018 Aug 1;164(2):379-390. doi: 10.1093/toxsci/kfy159. PMID: 29939355.
5. Cristol JP, Thiemermann C, Guérin MC, Torreilles J, de Paulet AC. L-Arginine infusion after ischaemia-reperfusion of rat kidney enhances lipid peroxidation. J Lipid Mediat Cell Signal. 1996 Jan;13(1):9-17. doi: 10.1016/0929-7855(95)00010-0. PMID: 8821807.
6. Kampan NC, Madondo MT, McNally OM, Quinn M, Plebanski M. Paclitaxel and Its Evolving Role in the Management of Ovarian Cancer. Biomed Res Int. 2015;2015:413076. doi: 10.1155/2015/413076. Epub 2015 Jun 7. PMID: 26137480; PMCID: PMC4475536.
7. Kubota T, Matsuzaki SW, Hoshiya Y, Watanabe M, Kitajima M, Asanuma F, et al. Antitumor activity of paclitaxel against human breast carcinoma xenografts serially transplanted into nude mice. J Surg Oncol. 1997 Feb;64(2):115-21. doi: 10.1002/(sici)1096-9098(199702)64:23.0.co;2-e. PMID: 9047247.
8. Kolomeichuk SN, Terrano DT, Lyle CS, Sabapathy K, Chambers TC. Distinct signaling pathways of microtubule inhibitors--vinblastine and Taxol induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent mechanisms, respectively. FEBS J. 2008 Apr;275(8):1889-99. doi: 10.1111/j.1742-4658.2008.06349.x. Epub 2008 Mar 13. PMID: 18341588.
9. Taxol (paclitaxel) injection label - FDA
10. Merouani A, Davidson SA, Schrier RW. Increased nephrotoxicity of combination taxol and cisplatin chemotherapy in gynecologic cancers as compared to cisplatin alone. Am J Nephrol. 1997;17(1):53-8. doi: 10.1159/000169072. PMID: 9057954.
11. Rabah SO. Acute Taxol nephrotoxicity: Histological and ultrastructural studies of mice kidney parenchyma. Saudi J Biol Sci. 2010 Apr;17(2):105-14. doi: 10.1016/j.sjbs.2010.02.003. Epub 2010 Feb 24. PMID: 23961065; PMCID: PMC3730725.
12. Motohashi N, Gallagher R, Anuradha V, Gollapudi R. Co-enzyme Q10 (Ubiquinone): It’s Implication in Improving the Life Style of the Elderly. Med Clin Rev. 2017;3:10. doi: 10.21767/2471-299X.1000052
13. Hodgson JM, Watts GF, Playford DA, Burke V, Croft KD Coenzyme Q10 improves blood pressure and glycaemic control: A controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr. 2002; 56: 1137-1142.
14. Schmelzer C, Lindner I, Rimbach G, Niklowitz P, Menke T, Döring F. Functions of coenzyme Q10 in inflammation and gene expression. Biofactors. 2008;32(1-4):179-83. doi: 10.1002/biof.5520320121. PMID: 19096114.
15. Villalba JM, Parrado C, Santos-Gonzalez M, Alcain FJ. Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations. Expert Opin Investig Drugs. 2010 Apr;19(4):535-54. doi: 10.1517/13543781003727495. PMID: 20367194.
16. Amal M. Mahfoz. Renal Protective Effects of Coenzyme Q10 Against Chromate Induced Nephrotoxicity in Rats. J App Sci. 2019, 19: 453-458.
17. Salman MI, Rashied RM, Hamad HM, Hamad HSH. The protective effect of coenzyme Q10 on experimental diabetic nephropathy in male rats. Eurasia J Biosci. 2020; 14: 6883-6888.
18. El-Sheikh AA, Morsy MA, Mahmoud MM, Rifaai RA, Abdelrahman AM. Effect of coenzyme-q10 on Doxorubicin-induced nephrotoxicity in rats. Adv Pharmacol Sci. 2012;2012:981461. doi: 10.1155/2012/981461. Epub 2012 Dec 17. PMID: 23346106; PMCID: PMC3533995.
19. Cordova-Gomez M, Galano A, Raul J, Alvarez-Idaboy JR. Piceatannol, a better peroxyl radical scavenger than resveratrol. RSC Advan. 2013; 3: 20209-20218
20. Kavas GO, Ayral PA, Elhan AH. The effects of resveratrol on oxidant/antioxidant systems and their cofactors in rats. Adv Clin Exp Med. 2013 Mar-Apr;22(2):151-5. PMID: 23709370.
21. Delmas D, Jannin B, Latruffe N. Resveratrol: preventing properties against vascular alterations and ageing. Mol Nutr Food Res. 2005 May;49(5):377-95. doi: 10.1002/mnfr.200400098. PMID: 15830334.
22. Koushki M, Amiri-Dashatan N, Ahmadi N, Abbaszadeh HA, Rezaei-Tavirani M. Resveratrol: A miraculous natural compound for diseases treatment. Food Sci Nutr. 2018;6(8):2473-2490. Published 2018 Oct 26. doi:10.1002/fsn3.855
23. Rafati A, Hoseini L, Babai A, Noorafshan A, Haghbin H, Karbalay-Doust S. Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study. Prev Nutr Food Sci. 2015 Dec;20(4):266-75. doi: 10.3746/pnf.2015.20.4.266. Epub 2015 Dec 31. PMID: 26770914; PMCID: PMC4700916.
24. Adikwu E, Biradee I, Ogungbaike TO. Therapeutic Benefit of resveratrol on 5-fluorouracil-induced nephrotoxicity in rats. J Biomed Res. 2019;6(2):11-16
25. Hu J, Zhang BO, Du L, Chen J , Lu Q. Resveratrol ameliorates cadmium induced renal oxidative damage and inflammation. Int J Clin Exp Med. 2017;10(5):7563-7572
26. Subramania P. Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2–Keap1 signaling. Biochim Biophys Acta Mol Basis Dis BBA-MOL BASIS DIS. 2011; 1812(7):719-731
27. Bash H, Ridha M. Coenzyme q10 amelorates cisplatin-induced nephrotoxicity in rats. Pharm Onl. 2018;3:49-56
28. Zendeboodi S, Esmaili A, Movahed A, Fatemikia H, Jamshidi A, Nazari M, et al. The attenuative effects of oral resveratrol on renal changes induced by vanadium injection in rats. J Renal Inj Prev. 2019;8(2):127-132.
29. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968 Oct 24;25(1):192-205. doi: 10.1016/0003-2697(68)90092-4. PMID: 4973948.
30. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973 Feb 9;179(4073):588-90. doi: 10.1126/science.179.4073.588. PMID: 4686466.
31. Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-6. doi: 10.1016/s0076-6879(84)05016-3. PMID: 6727660.
32. Sun M, Zigman S. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Anal Biochem. 1978 Oct 1;90(1):81-9. doi: 10.1016/0003-2697(78)90010-6. PMID: 727489.
33. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-10. doi: 10.1016/s0076-6879(78)52032-6. PMID: 672633.
34. Lameire N, Kruse V, Rottey S. Nephrotoxicity of anticancer drugs--an underestimated problem? Acta Clin Belg. 2011 Sep-Oct;66(5):337-45. doi: 10.2143/ACB.66.5.2062585. PMID: 22145268.
35. Arneson W. Electrolytes: The Salts of the Earth. Lab Med. 2014;45(1):11-15,
36. Holkar S, Vaishnav D , Hivre M. Study of Serum Electrolytes Levels in Patients with Diabetic Ketoacidosis IJHSR. 2014;9:154-157.
37. Al-Sayed E, Martiskainen O, Seif el-Din SH, Sabra AN, Hammam OA, El-Lakkany NM, Abdel-Daim MM. Hepatoprotective and antioxidant effect of Bauhinia hookeri extract against carbon tetrachloride-induced hepatotoxicity in mice and characterization of its bioactive compounds by HPLC-PDA-ESI-MS/MS. Biomed Res Int. 2014;2014:245171. doi: 10.1155/2014/245171. Epub 2014 May 14. PMID: 24955350; PMCID: PMC4053259.
38. Eldahshan OA, Abdel-Daim MM. Phytochemical study, cytotoxic, analgesic, antipyretic and anti-inflammatory activities of Strychnos nux-vomica. Cytotechnology. 2015 Oct;67(5):831-44. doi: 10.1007/s10616-014-9723-2. Epub 2014 Apr 8. PMID: 24711053; PMCID: PMC4545432.
39. Pandey KB, Rizvi S I .Anti-oxidative action of resveratrol: Implications for human health Arab J Chem. 2011,4(3):293-298.
40. Azab S, Abdel-Daim M, Eldahshan O. Phytochemical, cytotoxic, hepatoprotective and antioxidant properties of Delonix regialeaves extract. Med Chem Res. 2013;22(9):4269-4277.
41. Sato T, Ishikawa A, Homma Y. Effect of reduced form of coenzyme Q10 on cyclosporine nephrotoxicity. Exp Clin Transplant. 2013 Feb;11(1):17-20. doi: 10.6002/ect.2012.0126. Epub 2012 Nov 28. PMID: 23194328.
42. Silan C, Uzun O, Comunoğlu NU, Gokçen S, Bedirhan S, Cengiz M. Gentamicin-induced nephrotoxicity in rats ameliorated and healing effects of resveratrol. Biol Pharm Bull. 2007 Jan;30(1):79-83. doi: 10.1248/bpb.30.79. PMID: 17202664.
43. Tadolini B, Juliano C, Piu L, Franconi F, Cabrini L. Resveratrol inhibition of lipid peroxidation. Free Radic Res. 2000 Jul;33(1):105-14. doi: 10.1080/10715760000300661. PMID: 10826926.
44. Spanier G, Xu H, Xia N, Tobias S, Deng S, Wojnowski L, Forstermann U, Li H. Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol. 2009 Oct;60 Suppl 4:111-6. PMID: 20083859.
45. Eybl V, Kotyzová D, Cerná P, Koutensky J. Effect of melatonin, curcumin, quercetin, and resveratrol on acute ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative damage in rats. Hum Exp Toxicol. 2008 Apr;27(4):347-53. doi: 10.1177/0960327108094508. PMID: 18684806.
46. Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007 Sep;37(1):31-7. doi: 10.1007/s12033-007-0052-y. PMID: 17914161.
47. Gutierrez-Mariscal FM, Yubero-Serrano EM, Villalba JM, Lopez-Miranda J. Coenzyme Q10: From bench to clinic in aging diseases, a translational review. Crit Rev Food Sci Nutr. 2019;59(14):2240-2257. doi: 10.1080/10408398.2018.1442316. Epub 2018 Mar 13. PMID: 29451807.
48. Blatt T, Littarru GP. Biochemical rationale and experimental data on the antiaging properties of CoQ (10) at skin level. BioFactors. 2011;37: 381-5.