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Research Article

The Impact of L-Carnitine and Coenzyme Q10 as Protection Against Busulfan-Oxidative Stress in the Liver of Adult Rats

Author(s): Areeg M. Abdelrazek* and Shimaa A. Haredy*

Volume 10, Issue 5, 2020

Page: [578 - 586] Pages: 9

DOI: 10.2174/2210315509666190723131511

Price: $65

Abstract

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu.

Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues.

Material and Methods: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily.

Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10.

Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

Keywords: Busulfan, CoQ10, L-carnitine, oxidative stress, Caspase-3, hepatotoxicity.

Graphical Abstract

[1]
Abd-Elrazek, A.M.; Ahmed-Farid, O.A.H. Protective effect of Lcarnitine and L-arginine against busulfan-induced oligo-spermia in adult rat.Andrologia; , 2017, 50, . (1), p.e12806.
[PMID: 28444774]
[2]
Calléja, F.; Jansen, J.G.; Vrieling, H.; Laval, F.; van Zeeland, A.A. Modulation of the toxic and mutagenic effects induced by methyl methanesulfonate in Chinese hamster ovary cells by overexpression of the rat N-alkylpurine-DNA glycosylase. Mutat. Res., 1999, 425(2), 185-194.
[http://dx.doi.org/10.1016/S0027-5107(99)00034-2 ] [PMID: 10216211]
[3]
Sajedianfard, J.; Nazifi, S.; Izadi, A.; Chahardahcherik, M. Effect of various doses of silymarin on the oxidative stress induced by busulfan administration in the different organs of rats. Turk. J. Pharm. Sci., 2016, 13, 233-240.
[4]
Longo, N.; Amat di San Filippo, C.; Pasquali, M. Disorders of carnitine transport and the carnitine cycle. Am. J. Med. Genet. C. Semin. Med. Genet., 2006, 142C(2), 77-85.
[http://dx.doi.org/10.1002/ajmg.c.30087 ] [PMID: 16602102]
[5]
Longo, N.; Frigeni, M.; Pasquali, M. Carnitine transport and fatty acid oxidation. Biochim. Biophys. Acta, 2016, 1863(10), 2422-2435.
[http://dx.doi.org/10.1016/j.bbamcr.2016.01.023 ] [PMID: 26828774]
[6]
Sohet, F.M.; Neyrinck, A.M.; Pachikian, B.D.; de Backer, F.C.; Bindels, L.B.; Niklowitz, P.; Menke, T.; Cani, P.D.; Delzenne, N.M. Coenzyme Q10 supplementation lowers hepatic oxidative stress and inflammation associated with diet-induced obesity in mice. Biochem. Pharmacol., 2009, 78(11), 1391-1400.
[http://dx.doi.org/10.1016/j.bcp.2009.07.008 ] [PMID: 19632207]
[7]
Demiroren, K.; Dogan, Y.; Kocamaz, H.; Ozercan, I.H.; Ilhan, S.; Ustundag, B.; Bahcecioglu, I.H. Protective effects of L-carnitine, N-acetylcysteine and genistein in an experimental model of liver fibrosis. Clin. Res. Hepatol. Gastroenterol., 2014, 38(1), 63-72.
[http://dx.doi.org/10.1016/j.clinre.2013.08.014 ] [PMID: 24239319]
[8]
Reitman, S.; Frankel, S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am. J. Clin. Pathol., 1957, 28(1), 56-63.http://www.ncbi.nlm.nih.gov/pubmed/13458125
[http://dx.doi.org/10.1093/ajcp/28.1.56 ] [PMID: 13458125]
[9]
Papadoyannis, I.N.; Samanidou, V.F.; Nitsos, C.C. Simultaneous determination of nitrite and nitrate in drinking water and human serum by high performance anion-exchange chromatography and UV detection. J. Liq. Chromatogr. Relat. Technol., 1999, 22, 2023-2041.
[http://dx.doi.org/10.1081/JLC-100101783]
[10]
Karatas, F.; Karatepe, M.; Baysar, A. Determination of free malondialdehyde in human serum by high-performance liquid chromatography. Anal. Biochem., 2002, 311(1), 76-79.
[http://dx.doi.org/10.1016/S0003-2697(02)00387-1 ] [PMID: 12441155]
[11]
Jayatilleke, E.; Shaw, S. A high-performance liquid chromatographic assay for reduced and oxidized glutathione in biological samples. Anal. Biochem., 1993, 214(2), 452-457.
[http://dx.doi.org/10.1006/abio.1993.1522 ] [PMID: 8109733]
[12]
Hai, L.; Yueming, J.; Yunbo, L.; Weibo, J. A simple and rapid determination of ATP, ADP and AMP concentrations in peri-carp tissue of litchi fruit by high performance liquid chromatography. Food Technol. Biotechnol., 2006, 44, 531-534.
[13]
Lodovici, M.; Casalini, C.; Briani, C.; Dolara, P. Oxidative liver DNA damage in rats treated with pesticide mixtures. Toxicology, 1997, 117(1), 55-60.
[http://dx.doi.org/10.1016/S0300-483X(96)03553-6 ] [PMID: 9020199]
[14]
Bancroft, J.D.; Cook, H.C. Manual of Histological Techniques and Their Diagnostic Application; Churchill Livingstone: London, UK, 1994. https://books.google.com/books?id=R0prAAAAMAAJ&pgis=1
[15]
Ribeiro, M.P.C.; Castro e Santos, A.E.; Custódio, J.B.A. Mitochondrial dysfunction on the toxic effects of anticancer agents— From lab bench to bedside; Toxicol. Stud.- Cells, Drugs Environ, 2015, pp. 23-59.
[16]
Ray, S. Exploring protective role of ascorbic acid on Busulfaninduced lipid peroxidation, RJPBCS, , 975-8585.http://www.rjpbcs.com/pdf/2011_2(4)/74]./pdf
[17]
Kudryavtseva, A.V.; Krasnov, G.S.; Dmitriev, A.A.; Alekseev, B.Y.; Kardymon, O.L.; Sadritdinova, A.F.; Fedorova, M.S.; Pokrovsky, A.V.; Melnikova, N.V.; Kaprin, A.D.; Moskalev, A.A.; Snezhkina, A.V. Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget, 2016, 7(29), 44879-44905.
[http://dx.doi.org/10.18632/oncotarget.9821 ] [PMID: 27270647]
[18]
Dahlgren, S.; Holm, G.; Svanborg, N.; Watz, R. Clinical and morphological side-effects of busulfan (Myleran) treatment. Acta Medica. Scandinavica., 1972, 192, 129-135.
[19]
Deleve, L.D.; Wang, X. Role of oxidative stress and glutathione in Busulfan toxicity in cultured murine hepatocytes. Pharmacology, 2017, 60(3), 143-154.
[20]
Nagai, H.; Matsumaru, K.; Feng, G.; Kaplowitz, N. Reduced glutathione depletion causes necrosis and sensitization to tumor necrosis factor-α-induced apoptosis in cultured mouse hepatocytes. Hepatology, 2002, 36(1), 55-64.
[http://dx.doi.org/10.1053/jhep.2002.33995 ] [PMID: 12085349]
[21]
Feng, X.; Scheinberg, P.; Biancotto, A.; Rios, O.; Donaldson, S.; Wu, C.; Zheng, H.; Sato, K.; Townsley, D.M.; McCoy, J.P.; Young, N.S. In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia. Haematologica, 2014, 99(9), 1433-1440.
[http://dx.doi.org/10.3324/haematol.2014.106542 ] [PMID: 24907357]
[22]
Jones, K.L.; Mansell, A.; Patella, S.; Scott, B.J.; Hedger, M.P.; de Kretser, D.M.; Phillips, D.J. Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia. Proc. Natl. Acad. Sci. USA, 2007, 104(41), 16239-16244.
[http://dx.doi.org/10.1073/pnas.0705971104 ] [PMID: 17911255]
[23]
Underwood, J.C.; Shahani, R.T.; Blackburn, E.K. Cholestatic jaundice following treatment of chronic granulocytic leukemia with busulphan. J. Clin. Pathol., 1970, 23(9), 827.
[http://dx.doi.org/10.1136/jcp.23.9.827-b ] [PMID: 5278972]
[24]
Demirdag, K.; Bahcecioglu, I.H.; Ozercan, I.H.; Özden, M.; Yilmaz, S.; Kalkan, A. Role of L-carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats. J. Gastroenterol. Hepatol., 2004, 19(3), 333-338.
[http://dx.doi.org/10.1111/j.1440-1746.2003.03291.x ] [PMID: 14748882]
[25]
Selimoglu, M.A.; Aydogdu, S.; Yagci, R.V.; Huseyinov, A. Plasma and liver carnitine status of children with chronic liver disease and cirrhosis. Pediatr. Int., 2001, 43(4), 391-395.
[http://dx.doi.org/10.1046/j.1442-200X.2001.01423.x ] [PMID: 11472585]
[26]
Kidd, P.M. Glutathione: Systemic protectant against oxidative and free radical damage. Altern. Med. Rev., 1997, 2, 155-176.
[27]
Bykov, I.; Järveläinen, H.; Lindros, K. L-carnitine alleviates alcohol-induced liver damage in rats: role of tumour necrosis factoralpha. Alcohol Alcohol., 2003, 38(5), 400-406.
[http://dx.doi.org/10.1093/alcalc/agg109 ] [PMID: 12915513]
[28]
Fouad, A.A.; Jresat, I. Hepatoprotective effect of coenzyme Q10 in rats with acetaminophen toxicity. Environ. Toxicol. Pharmacol., 2012, 33(2), 158-167.
[http://dx.doi.org/10.1016/j.etap.2011.12.011 ] [PMID: 22222558]
[29]
Liu, H.-T.; Huang, Y.-C.; Cheng, S.-B.; Huang, Y.-T.; Lin, P.-T. Effects of coenzyme Q10 supplementation on antioxidant capacity and inflammation in hepatocellular carcinoma patients after surgery: A randomized, placebo-controlled trial. Nutr. J., 2016, 15(1), 85.
[http://dx.doi.org/10.1186/s12937-016-0205-6 ] [PMID: 27716246]
[30]
DeLeve, L.D.; Wang, X. Role of oxidative stress and glutathione in busulfan toxicity in cultured murine hepatocytes. Pharmacology, 2000, 60(3), 143-154.
[http://dx.doi.org/10.1159/000028359 ] [PMID: 10754451]

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