EFFECTS OF VITAMIN E AND COENZYME Q10 SUPPLEMENTATION AGAINST DOXORUBICIN-INDUCED NEUROTOXICITY IN RATS:ROLE OF APOPTOSIS

Authors

  • Manal Abdulkhaliq Ibrahim Department of Pharmacology and Toxicology, College of Pharmacy, University of Basra, Basra, Iraq.
  • Nada Naji Al-shawi Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

DOI:

https://doi.org/10.22159/ajpcr.2018.v11i9.27851

Keywords:

Vitamin E, Coenzyme Q10, Doxorubicin, Neurotoxicity, TUNEL-assay, caspase-3

Abstract

Objective: This work was designed to investigate the effect of Vitamin E and the coenzyme Q10 (CoQ10) supplementation on neurotoxicity induced by doxorubicin (DOX) in rats.

Methods: Forty-nine adult Albino rats of both sexes were utilized in this study; animals were randomly enrolled into seven groups of seven animals each. Group I: Control (rats administered corn oil); Group II: Vitamin E at a dose of 100 mg/kg/day for 3 weeks; Group III: CoQ10 at a dose of 50 mg/kg/day for 3 weeks; Group IV: DOX (2.5 mg/kg) intraperitoneally (IP) injected every other day for 2 weeks; Group V: Vitamin E (100 mg/kg/day) orally administered for 3 weeks prior to a DOX 2.5 mg/kg IP injected every other day for 2 weeks; Group VI: CoQ10 (50 mg/kg/day) for 3 weeks orally administered prior to an IP dose of DOX 2.5 mg/kg every other day for 2 weeks; and Group VII: CoQ10 (50 mg/kg/day), Vitamin E (100 mg/kg) for 3 weeks orally administered prior to an IP dose of DOX 2.5 mg/kg every other day for 2 weeks. Twenty-four hour after the end of the treatment duration, brain of each animal was excised and part of it to be utilized to prepare homogenate for the estimation of caspase-3 (CASP-3), and the remaining part is used for immunohistochemistry examination and to estimate the percent of apoptotic index by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay.

Results: Vitamin E and CoQ10 significantly (p<0.05) reduced CASP-3, reduced the percent apoptotic index of TUNEL-assay, and there was an improvement in the immunohistochemistry of rats' brain in Groups V, Group VI, and group VII by reducing number of apoptotic cells compared to Group IV.

Conclusion: Both Vitamin E and CoQ10 may have a protective effect against DOX-induced neurotoxicity in rats.

Downloads

Download data is not yet available.

Author Biography

Manal Abdulkhaliq Ibrahim, Department of Pharmacology and Toxicology, College of Pharmacy, University of Basra, Basra, Iraq.

department pharmacology and toxicology

References

Sener SF, Grey N. The global burden of cancer. J Surg Oncol 2005;92:1-3.

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.

Urruticoechea A, Alemany R, Balart J, Villanueva A, Viñals F, Capellá G, et al. Recent advances in cancer therapy: An overview. Curr Pharm Des 2010;16:3-10.

Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 2004;4:423-36.

Maria A. Mitry, John G. Doxorubicin induced heart failure: Phenotype and molecular mechanisms.IJC Heart Vasc 2016;10:17-24.

Cutts SM, Swift LP, Rephaeli A, Nudelman A, Phillips DR. Sequence specificity of adriamycin-DNA adducts in human tumor cells. Mol Cancer Ther 2003;2:661-70.

Jansen CE, Dodd MJ, Miaskowski CA, Dowling GA, Kramer J. Preliminary results of a longitudinal study of changes in cognitive function in breast cancer patients undergoing chemotherapy with doxorubicin and cyclophosphamide. Psychooncology 2008;17:1189-95.

Merzoug S, Toumi ML, Boukhris N, Baudin B, Tahraoui A. Adriamycin-related anxiety-like behavior, brain oxidative stress and myelotoxicity in male wistar rats. Pharmacol Biochem Behav 2011;99:639-47.

Banks WA, Erickson MA. The blood-brain barrier and immune function and dysfunction. Neurobiol Dis 2010;37:26-32.

Kipnis J, Derecki NC, Yang C, Scrable H. Immunity and cognition: What do age-related dementia, HIV-dementia and chemo-brain†have in common? Trends Immunol 2008;29:455-63.

Schlatter MC, Cameron LD. Emotional suppression tendencies as predictors of symptoms, mood, and coping appraisals during AC chemotherapy for breast cancer treatment. Ann Behav Med 2010;40:15-29.

Packer L, Weber SU, Rimbach G. Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. J Nutr 2001;131:369S-73S.

Imounan F, Bouslam N, Aasfara J, Alaoui KE, Regragui W, Haddou EA, et al Vitamin E in ataxia and neurodegenerative diseases: A review. World J Neurosci 2012;2:217-22.

Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr 2001;20:591-8.

Overvad K, Diamant B, Holm L, Holmer G, Mortensen SA, Stender S, et al. Coenzyme Q10 in health and disease. Eur J Clin Nutr 1999;53:764-70.

Chapidze G, Kapanadze S, Dolidze N, Bachutashvili Z, Latsabidze N. Prevention of coronary atherosclerosis by the use of combination therapy with antioxidant coenzyme Q10 and statins. Georgian Med News 2005;118:20-5.

Rosenfeldt F, Hilton D, Pepe S, Krum H. Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure. Biofactors 2003;18:91-100.

Sarter B. Coenzyme Q10 and cardiovascular disease: A review. J Cardiovasc Nurs 2002;16:9-20.

Galal MK, Khalaf AA, Ogaly HA, Ibrahim MA. Vitamin E attenuates neurotoxicity induced by deltamethrin in rats. BMC Complement Altern Med 2014;14:458.

Kandhare A, Ghosh P, Ghule A, Bodhankar S. Elucidation of molecular mechanism involved in neuroprotective effect of coenzyme Q10 in alcohol-induced neuropathic pain. Fundam Clin Pharmacol 2013;27:603-22.

Mohamed RH, Karam RA, Amer MG. Epicatechin attenuates doxorubicin-induced brain toxicity: Critical role of TNF-α, iNOS and NF-κB. Brain Res Bull 2011;86:22-8.

Kreisel T, Frank MG, Licht T, Reshef R, Ben-Menachem-Zidon O, Baratta MV, et al. Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis. Mol Psychiatry 2014;19:699-709.

Post A, Rücker M, Ohl F, Uhr M, Holsboer F, Almeida OF, et al. Mechanisms underlying the protective potential of alpha-tocopherol (vitamin E) against haloperidol-associated neurotoxicity. Neuropsychopharmacology 2002;26:397-407.

Haendeler J, Zeiher AM, Dimmeler S. Vitamin C and E prevent lipopolysaccharide-induced apoptosis in human endothelial cells by modulation of bcl-2 and bax. Eur J Pharmacol 1996;317:407-11.

Siler-Marsiglio KI, Shaw G, Heaton MB. Pycnogenol and vitamin E inhibit ethanol-induced apoptosis in rat cerebellar granule cells. J Neurobiol 2004;59:261-71.

Tawfik MK. Coenzyme Q10 enhances the anticonvulsant effect of phenytoin in pilocarpine-induced seizures in rats and ameliorates phenytoin-induced cognitive impairment and oxidative stress. Epilepsy Behav 2011;22:671-7.

Li H, Chen G, Ma W, Li PA. Water-soluble coenzyme q10 inhibits nuclear translocation of apoptosis inducing factor and cell death caused by mitochondrial complex I inhibition. Int J Mol Sci 2014;15:13388-400.

Hwang JY, Min SW, Jeon YT, Hwang JW, Park SH, Kim JH, et al. Effect of coenzyme Q10 on spinal cord ischemia-reperfusion injury. J Neurosurg Spine 2015;22:432-8.

Published

07-09-2018

How to Cite

Ibrahim, M. A., and N. N. Al-shawi. “EFFECTS OF VITAMIN E AND COENZYME Q10 SUPPLEMENTATION AGAINST DOXORUBICIN-INDUCED NEUROTOXICITY IN RATS:ROLE OF APOPTOSIS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 11, no. 9, Sept. 2018, pp. 402-6, doi:10.22159/ajpcr.2018.v11i9.27851.

Issue

Section

Original Article(s)